The Effects of Ustekinumab on Health-related Quality of Life in Patients With Moderate to Severe Crohn’s Disease

The Effects of Ustekinumab on Health-related Quality of Life in Patients With Moderate to Severe... Abstract Background and Aims We assessed the effect of ustekinumab on health-related quality of life [HRQOL] in adults with Crohn’s disease [CD]. Methods Patients with moderately to severely active CD and inadequate response or intolerance to tumour necrosis factor antagonists [UNITI-1, n = 741], or conventional therapy [UNITI-2, n = 627] were randomised to placebo, ustekinumab 130 mg, or 6 mg/kg intravenous induction therapy. At Week 8, ustekinumab-treated responders (Crohn’s Disease Activity Index [CDAI] reduction ≥100 or CDAI <150 points) were re-randomised to subcutaneous maintenance therapy [IM-UNITI, n = 388] with placebo, ustekinumab 90 mg every 12 weeks [q12w], or ustekinumab 90 mg every 8 weeks [q8w], for 44 additional weeks. Inflammatory Bowel Disease Questionnaire [IBDQ] and 36-item Short Form Health Survey [SF-36] physical component summary [PCS] and mental component summary [MCS] scores were completed at induction baseline and Week 8, and at maintenance Weeks 20 and 44. Clinically meaningful improvement in IBDQ and PCS and MCS scores were evaluated. For all HRQOL outcomes, each ustekinumab dose and placebo were compared. Results Induction baseline mean values of IBDQ, PCS, and MCS were similar across groups, but impaired relative to general population norms. At Week 8, ustekinumab induced greater improvement than placebo in both HRQOL scores. Significantly greater proportions of patients receiving ustekinumab 6 mg/kg or 130 mg had clinically meaningful IBDQ improvement [UNITI-1: 54.8%, 46.9% versus 36.5%, respectively; UNITI-2: 68.1%, 58.7% versus 41.1%, respectively; p <0.05, all comparisons]. Similarly, greater proportions of ustekinumab-treated patients in both studies had clinically meaningful improvements in PCS and MCS as compared with placebo. At Week 44, improvements in IBDQ, PCS, and MCS scores were maintained with ustekinumab. Conclusions Ustekinumab improved HRQOL in patients with moderately to severely active CD. Patient-reported outcomes, inflammatory bowel disease questionnaire, medical outcome survey short form-36 1. Introduction Crohn’s disease [CD] often has important negative effects on patients’ health-related quality of life [HRQOL], because of the impacts of disease on both physical and mental well-being. HRQOL is usually assessed by either the 36-item Short-Form Health Survey [SF-36], a generic multi-item scale that evaluates both physical [PCS] and mental component summary scores [MCS],1 or a disease-specific instrument: the Inflammatory Bowel Disease Questionnaire [IBDQ].2 Previous studies have shown that SF-36 is a reliable and valid instrument to measure general health status in patients with CD.3 Importantly, as can only be determined using a generic instrument, patients with CD have substantially impaired HRQOL compared with the general population.4 Furthermore, the effects of the disease on SF-36 MCS scores is relatively more profound than observed in other chronic inflammatory diseases such as rheumatoid arthritis. The IBDQ, a 32-item questionnaire comprising four domains [bowel symptoms, systemic symptoms, emotional function, and social function] is the most commonly used disease-specific measure for evaluation of HRQOL in CD. The IBDQ is more sensitive than the SF-36 to clinically meaningful changes in health status, and therefore can be used to detect relatively small differences in treatment effects in specific disease subgroups or drug treatment regimens. Ustekinumab, a monoclonal antibody to the p40 subunit of interleukins [IL]-12 and -23, is approved for the treatment of active CD based on the results of three Phase 3 studies.5 Herein we report the effects of ustekinumab on HRQOL in patients with moderate to severe CD. 2. Methods The UNITI and IM-UNITI studies were multicentre, randomised, double-blind, placebo-controlled Phase 3 studies designed to evaluate the safety and efficacy of ustekinumab induction and maintenance therapy in patients with moderately to severely active CD. Briefly, patients with moderately to severely active CD (defined by a CD Activity Index [CDAI] score of 220–450) and with inadequate response or intolerance to tumour necrosis factor [TNF] antagonists [UNITI-1] or conventional therapy [UNITI-2], were randomised in a 1:1:1 ratio to receive a single intravenous [IV] infusion of placebo, ustekinumab 130 mg, or weight-range based dosing of approximately 6 mg/kg ustekinumab (260 mg [weight ≤55 kg], 390 mg [weight >55 kg and ≤85 kg], or 520 mg [weight >85 kg], hereafter referred to as 6 mg/kg). Patients with a clinical response [defined as a CDAI reduction ≥100 points or CDAI <150] to ustekinumab at Week 8 were re-randomised into the primary maintenance population in IM-UNITI to receive subcutaneous [SC] placebo, or ustekinumab 90 mg every 12 weeks [q12w], or ustekinumab 90 mg every 8 weeks [q8w], through Week 44 [52 weeks after induction baseline]. 2.1. Assessments Disease-specific HRQOL was measured using the Inflammatory Bowel Disease Questionnaire [IBDQ],2 and generic HRQOL was measured using the SF-361 summary scores [PCS and MCS] and individual item scores, which were completed at Weeks 0 and 8 of the induction studies and at Weeks 20 and 44 of the maintenance study. Clinically meaningful improvements of these measures were defined as an increase of ≥16 points in IBDQ score2,6,7 and ≥5 points in SF-36 PCS and MCS scores.8,9 Patients with an IBDQ score ≥170 points were considered to be in clinical remission.10 Additionally, IBDQ normalisation defined as a score ≥210 points,7 and SF-36 PCS or MCS normalisation defined as scores ≥50 points11 among patients with abnormal baseline values, were also evaluated in post hoc analyses. 2.2. Statistical analysis The Type 1 error rate within each study was controlled at 0.05 for the primary and major secondary endpoints, using a hierarchical testing procedure. The HRQOL outcomes described herein were pre-specified; however, statistical contrasts were not adjusted for multiplicity. thus p-values should be considered nominal. Each ustekinumab group [induction: ustekinumab 130 mg, ustekinumab 6 mg/kg, ustekinumab combined; maintenance: ustekinumab 90 mg q12w, ustekinumab 90 mg q8w] was compared with the placebo group. Continuous outcomes [mean change from baseline in SF-36 component summary and scale scores at Week 8, Week 20, and Week 44; mean change from baseline in IBDQ total and domain scores at Week 8, Week 20, and Week 44] were analysed by analysis of covariance on van der Waerden normal scores. Proportions of patients with dichotomous outcomes [clinically meaningful improvements or normalised values] in IBDQ, PCS, and MCS at Week 8 and Week 44 were compared using a Cochran-Mantel-Haenszel chi-square test. The following missing data conventions were used for these analyses. Each of the four individual IBDQ dimensions was calculated when ≤1 item was missing in the dimension. The missing item was estimated using the average value across the non-missing items. If any one of the dimensions within the IBDQ could not be calculated, then the total IBDQ score was not be calculated. For SF-36 scores, subscales were calculated whenever ≥50% of the items that comprised the individual subscale were available [non-missing]. Any missing items were estimated using the average value across the non-missing items for that subscale. If <50% of the items that comprised the subscale were available, the subscale was not calculated. If any of the individual subscales that comprised the PCS or MCS score was missing, then these scores could not be calculated. 3. Results 3.1. Induction studies Baseline disease characteristics in both the UNITI-1 and UNITI-2 study populations were representative of patients with moderately to severely active CD refractory to either TNF antagonists [UNITI-1] or conventional therapies [UNITI-2]. Median disease duration was 6.4 and 10.1 years and median CDAI scores were 292.5 and 317.0 in UNITI-2 and 1, respectively. Median C-reactive protein [CRP] concentrations were 8.05 mg/L in UNITI-2 and 9.88 mg/L in UNITI-1. Higher values for CDAI score and CRP concentrations are consistent with higher disease activity in the TNF-antagonist failure UNITI-1 population. 3.1.1. IBDQ results In both UNITI-1 and UNITI-2, mean (standard deviation[SD]) baseline IBDQ scores for placebo, ustekinumab 130 mg, and ustekinumab 6 mg/kg (UNITI-1: 120.0 [29.27], 119.5 [29.47], and 118.2 [26.64], respectively; UNITI-2: 122.7 [31.32], 118.2 [30.99], and 122.8 [31.62], respectively) were similar across treatment groups, consistent with substantially impaired HRQOL. Following initiation of induction therapy, significantly greater improvement was observed for both ustekinumab doses in comparison with placebo [Table 1; Figure 1A, B]. A numerically greater treatment effect relative to placebo was seen in UNITI-2 than UNITI-1 [ustekinumab 130 mg, 14.4 versus 6.2; ustekinumab 6 mg/kg, 20.6 versus 10.2, respectively]. Table 1. Mean [SD] and mean change [SD] from baseline in the IBDQ and SF-36 scores at Week 8 of induction therapy. UNITI-1 UNITI-2 Ustekinumab Ustekinumab Patient- reportedOutcome Placebo 130 mg 6 mg/kga Combined Placebo 130 mg 6 mg/kga Combined IBDQ score, n = 247 245 249 494 209 209 209 418 Baseline, n 244 243 248 491 207 208 207 415 Mean [SD] 120.0 [29.27] 119.5 [29.47] 118.2 [26.64] 118.8 [28.06] 122.7 [31.32] 118.2 [30.99] 122.8 [31.62] 120.5 [31.35] Week 8, n 244 243 248 491 207 208 207 415 Mean [SD] 131.9 [34.61] 137.5 [37.95] 140.3 [34.39] 138.9 [36.19] 137.3 [37.33] 147.3 [36.74] 158.0 [34.54] 152.6 [36.02] Change from baseline Week 8b,c, n 244 243 248 491 207 208 207 415 Mean [SD] 11.9 [26.51] 18.1* [28.02] 22.1*** [28.59] 20.1*** [28.35] 14.7 [26.96] 29.1*** [33.82] 35.3*** [36.05] 32.2*** [35.04] SF-36 score, n 225 231 235 466 190 194 196 390 Physical component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [7.12] 37.8 [7.12] 37.2 [7.09] 37.5 [7.11] 39.7 [7.19] 38.9 [7.62] 38.9 [7.05] 38.9 [7.33]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.4 [7.56] 41.0 [8.32] 40.7 [8.48] 40.9 [8.39] 42.3 [7.79] 44.0 [8.39] 44.9 [8.75] 44.4 [8.57]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.6 [6.50] 3.2 [6.43] 3.6 [6.75] 3.4 [6.60] 2.6 [5.88] 5.1** [7.24] 6.0*** [7.70] 5.5*** [7.48] Mental component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [10.64] 37.3 [9.98] 36.4 [9.89] 36.9 [9.93] 37.1 [10.75] 37.2 [10.81] 37.9 [11.15] 37.6 [10.98]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.0 [11.38] 40.6 [11.79] 41.3 [10.45] 41.0 [11.13] 40.4 [11.79] 43.1 [11.36] 44.7 [10.72] 43.9 [11.06]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.2 [8.47] 3.3 [9.41] 4.9** [9.28] 4.1* [9.37] 3.3 [9.47] 5.9** [10.55] 6.8*** [11.34] 6.4*** [10.95] UNITI-1 UNITI-2 Ustekinumab Ustekinumab Patient- reportedOutcome Placebo 130 mg 6 mg/kga Combined Placebo 130 mg 6 mg/kga Combined IBDQ score, n = 247 245 249 494 209 209 209 418 Baseline, n 244 243 248 491 207 208 207 415 Mean [SD] 120.0 [29.27] 119.5 [29.47] 118.2 [26.64] 118.8 [28.06] 122.7 [31.32] 118.2 [30.99] 122.8 [31.62] 120.5 [31.35] Week 8, n 244 243 248 491 207 208 207 415 Mean [SD] 131.9 [34.61] 137.5 [37.95] 140.3 [34.39] 138.9 [36.19] 137.3 [37.33] 147.3 [36.74] 158.0 [34.54] 152.6 [36.02] Change from baseline Week 8b,c, n 244 243 248 491 207 208 207 415 Mean [SD] 11.9 [26.51] 18.1* [28.02] 22.1*** [28.59] 20.1*** [28.35] 14.7 [26.96] 29.1*** [33.82] 35.3*** [36.05] 32.2*** [35.04] SF-36 score, n 225 231 235 466 190 194 196 390 Physical component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [7.12] 37.8 [7.12] 37.2 [7.09] 37.5 [7.11] 39.7 [7.19] 38.9 [7.62] 38.9 [7.05] 38.9 [7.33]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.4 [7.56] 41.0 [8.32] 40.7 [8.48] 40.9 [8.39] 42.3 [7.79] 44.0 [8.39] 44.9 [8.75] 44.4 [8.57]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.6 [6.50] 3.2 [6.43] 3.6 [6.75] 3.4 [6.60] 2.6 [5.88] 5.1** [7.24] 6.0*** [7.70] 5.5*** [7.48] Mental component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [10.64] 37.3 [9.98] 36.4 [9.89] 36.9 [9.93] 37.1 [10.75] 37.2 [10.81] 37.9 [11.15] 37.6 [10.98]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.0 [11.38] 40.6 [11.79] 41.3 [10.45] 41.0 [11.13] 40.4 [11.79] 43.1 [11.36] 44.7 [10.72] 43.9 [11.06]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.2 [8.47] 3.3 [9.41] 4.9** [9.28] 4.1* [9.37] 3.3 [9.47] 5.9** [10.55] 6.8*** [11.34] 6.4*** [10.95] IBDQ, Inflammatory Bowel Disease Questionnaire; SD, standard deviation; SF-36, 36-Item Short Form Health Survey. aWeight-range based ustekinumab doses approximating 6 mg/kg: 260 mg [weight ≤55 kg], 390 mg [weight >55 kg and ≤85 kg], 520 mg [weight >85 kg]. bPatients who had a prohibited Crohn’s disease-related surgery or had prohibited concomitant medication changes before Week 8 had their baseline value carried forward. cPatients who had insufficient data at Week 8 had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Table 1. Mean [SD] and mean change [SD] from baseline in the IBDQ and SF-36 scores at Week 8 of induction therapy. UNITI-1 UNITI-2 Ustekinumab Ustekinumab Patient- reportedOutcome Placebo 130 mg 6 mg/kga Combined Placebo 130 mg 6 mg/kga Combined IBDQ score, n = 247 245 249 494 209 209 209 418 Baseline, n 244 243 248 491 207 208 207 415 Mean [SD] 120.0 [29.27] 119.5 [29.47] 118.2 [26.64] 118.8 [28.06] 122.7 [31.32] 118.2 [30.99] 122.8 [31.62] 120.5 [31.35] Week 8, n 244 243 248 491 207 208 207 415 Mean [SD] 131.9 [34.61] 137.5 [37.95] 140.3 [34.39] 138.9 [36.19] 137.3 [37.33] 147.3 [36.74] 158.0 [34.54] 152.6 [36.02] Change from baseline Week 8b,c, n 244 243 248 491 207 208 207 415 Mean [SD] 11.9 [26.51] 18.1* [28.02] 22.1*** [28.59] 20.1*** [28.35] 14.7 [26.96] 29.1*** [33.82] 35.3*** [36.05] 32.2*** [35.04] SF-36 score, n 225 231 235 466 190 194 196 390 Physical component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [7.12] 37.8 [7.12] 37.2 [7.09] 37.5 [7.11] 39.7 [7.19] 38.9 [7.62] 38.9 [7.05] 38.9 [7.33]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.4 [7.56] 41.0 [8.32] 40.7 [8.48] 40.9 [8.39] 42.3 [7.79] 44.0 [8.39] 44.9 [8.75] 44.4 [8.57]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.6 [6.50] 3.2 [6.43] 3.6 [6.75] 3.4 [6.60] 2.6 [5.88] 5.1** [7.24] 6.0*** [7.70] 5.5*** [7.48] Mental component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [10.64] 37.3 [9.98] 36.4 [9.89] 36.9 [9.93] 37.1 [10.75] 37.2 [10.81] 37.9 [11.15] 37.6 [10.98]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.0 [11.38] 40.6 [11.79] 41.3 [10.45] 41.0 [11.13] 40.4 [11.79] 43.1 [11.36] 44.7 [10.72] 43.9 [11.06]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.2 [8.47] 3.3 [9.41] 4.9** [9.28] 4.1* [9.37] 3.3 [9.47] 5.9** [10.55] 6.8*** [11.34] 6.4*** [10.95] UNITI-1 UNITI-2 Ustekinumab Ustekinumab Patient- reportedOutcome Placebo 130 mg 6 mg/kga Combined Placebo 130 mg 6 mg/kga Combined IBDQ score, n = 247 245 249 494 209 209 209 418 Baseline, n 244 243 248 491 207 208 207 415 Mean [SD] 120.0 [29.27] 119.5 [29.47] 118.2 [26.64] 118.8 [28.06] 122.7 [31.32] 118.2 [30.99] 122.8 [31.62] 120.5 [31.35] Week 8, n 244 243 248 491 207 208 207 415 Mean [SD] 131.9 [34.61] 137.5 [37.95] 140.3 [34.39] 138.9 [36.19] 137.3 [37.33] 147.3 [36.74] 158.0 [34.54] 152.6 [36.02] Change from baseline Week 8b,c, n 244 243 248 491 207 208 207 415 Mean [SD] 11.9 [26.51] 18.1* [28.02] 22.1*** [28.59] 20.1*** [28.35] 14.7 [26.96] 29.1*** [33.82] 35.3*** [36.05] 32.2*** [35.04] SF-36 score, n 225 231 235 466 190 194 196 390 Physical component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [7.12] 37.8 [7.12] 37.2 [7.09] 37.5 [7.11] 39.7 [7.19] 38.9 [7.62] 38.9 [7.05] 38.9 [7.33]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.4 [7.56] 41.0 [8.32] 40.7 [8.48] 40.9 [8.39] 42.3 [7.79] 44.0 [8.39] 44.9 [8.75] 44.4 [8.57]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.6 [6.50] 3.2 [6.43] 3.6 [6.75] 3.4 [6.60] 2.6 [5.88] 5.1** [7.24] 6.0*** [7.70] 5.5*** [7.48] Mental component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [10.64] 37.3 [9.98] 36.4 [9.89] 36.9 [9.93] 37.1 [10.75] 37.2 [10.81] 37.9 [11.15] 37.6 [10.98]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.0 [11.38] 40.6 [11.79] 41.3 [10.45] 41.0 [11.13] 40.4 [11.79] 43.1 [11.36] 44.7 [10.72] 43.9 [11.06]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.2 [8.47] 3.3 [9.41] 4.9** [9.28] 4.1* [9.37] 3.3 [9.47] 5.9** [10.55] 6.8*** [11.34] 6.4*** [10.95] IBDQ, Inflammatory Bowel Disease Questionnaire; SD, standard deviation; SF-36, 36-Item Short Form Health Survey. aWeight-range based ustekinumab doses approximating 6 mg/kg: 260 mg [weight ≤55 kg], 390 mg [weight >55 kg and ≤85 kg], 520 mg [weight >85 kg]. bPatients who had a prohibited Crohn’s disease-related surgery or had prohibited concomitant medication changes before Week 8 had their baseline value carried forward. cPatients who had insufficient data at Week 8 had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Figure 1. View largeDownload slide Mean baseline and Week 8, and mean change in IBDQ, PCS, and MCS scores with induction therapy [UNITI-1: A, C, E; UNITI-2: B, D, F]. Figure 1. View largeDownload slide Mean baseline and Week 8, and mean change in IBDQ, PCS, and MCS scores with induction therapy [UNITI-1: A, C, E; UNITI-2: B, D, F]. For both studies, changes in the mean IBDQ scores at Week 8 were significantly greater in both ustekinumab dose groups compared with placebo and across all dimensions [p <0.05 for all comparisons]. In both studies, changes in the mean IBDQ dimension scores at Week 8 were significantly greater in the ustekinumab 6 mg/kg group compared with placebo and across all dimensions [p <0.001 for all comparisons]. In the ustekinumab 130 mg group, mean changes at Week 8 were significantly greater for the social and systemic dimensions [p <0.05 for both comparisons], and numerically greater for the bowel and emotional dimensions compared with placebo in UNITI-1 [Table 2]. Mean changes at Week 8 were significantly greater across all four dimensions when compared with placebo [p <0.001 for both comparisons] in UNITI-2 [Table 2]. Table 2. Mean [SD] and mean change [SD] from baseline in IBDQ domain and SF-36 scale scores at Week 8 of induction therapy. UNITI-1 UNITI-2 Patient-reportedoutcome Ustekinumab Ustekinumab Placebo 130 mg 6 mga Placebo 130 mg 6 mga IBDQ score, nb,c 247 245 249 209 209 209 Bowel symptoms  Baseline, n  Mean [SD] 245 38.6 [9.28] 244 38.2 [8.81] 248 38.5 [8.27] 207 38.8 [9.14] 209 38.2 [9.21] 208 38.9 [9.19]  Week 8, n  Mean [SD] 245 42.6 [10.31] 244 43.7 [11.27] 248 45.1 [10.01] 207 43.9 [11.02] 209 47.5[10.96] 208 50.6 [10.88]  Change at Week 8, n  Mean [SD] 245 4.0 [8.81] 244 5.5 [9.04] 248 6.6*** [8.56] 207 5.1 [8.78] 209 9.3*** [10.76] 208 11.7*** [11.21] Emotional functions  Baseline, n  Mean [SD] 245 46.5 [13.32] 243 47.0 [13.75] 248 45.9 [11.93] 207 46.7 [14.17] 209 44.3 [13.56] 208 46.8 [14.44]  Week 8, n  Mean [SD] 245 50.7 [14.99] 243 52.8 [16.06] 248 53.7 [14.20] 207 51.2 [15.71] 209 54.5 [15.28] 208 58.6 [14.43]  Change at Week 8, n  Mean [SD] 245 4.2 [10.52] 243 5.8 [11.53] 248 7.7*** [11.82] 207 4.5 [10.79] 209 10.1*** [13.95] 208 11.9*** [14.88] Systemic symptoms Baseline, n Mean [SD] 245 15.2 [5.25] 245 14.9 [4.74] 248 14.6 [4.97] 209 15.7 [5.35] 209 15.2 [5.11] 208 15.8 [5.23] Week 8, n Mean [SD] 245 17.3 [6.09] 245 18.3 [6.52] 248 18.5 [6.60] 209 18.5 [6.46] 209 20.0 [6.61] 208 21.8 [5.94] Change at Week 8, n Mean [SD] 245 2.1 [5.10] 245 3.4* [5.65] 248 3.9*** [5.57] 209 2.8 [5.17] 209 4.8*** [6.09] 208 6.0*** [6.29] Social functions Baseline Mean [SD] 244 19.8 [7.35] 244 19.3 [7.44] 248 19.2 [7.15] 209 21.5 [7.21] 208 20.4 [7.44] 209 21.4 [7.37] Week 8 n Mean [SD] 244 21.3 [8.09] 244 22.6 [8.23] 248 23.0 [7.99] 209 23.8 [7.75] 208 25.2 [7.65] 209 26.9 [6.97] Change at Week 8, n, Mean [SD] 244 1.5 [6.03] 244 3.3** [6.14] 248 3.8*** [6.63] 209 2.3 [5.67] 208 4.8*** [6.69] 209 5.6*** [7.12] SF-36 Score, n=b,c 225 231 235 190 194 196 Physical functioning Baseline, n Mean [SD] 224 44.2 [8.52] 231 44.3 [8.61] 234 43.5 [8.70] 190 44.9 [9.57] 193 44.2 [9.38] 196 43.7 [9.13] Week 8, n Mean [SD] 224 45.9 [8.67] 231 46.7 [9.23] 234 45.9 [9.52] 190 46.6 [9.21] 193 47.9 [8.45] 196 47.9 [8.65] Change at Week 8, n Mean [SD] 224 1.7 [6.58] 231 2.4 [6.76] 234 2.4 [7.27] 190 1.8 [6.68] 193 3.7* [7.36] 196 4.2** [7.09] Role-physical Baseline, n Mean [SD] 223 35.2 [8.87] 231 35.5 [9.51] 234 34.7 [9.45] 190 37.7 [9.36] 193 37.2 [9.92] 195 37.1 [9.64] Week 8, n Mean [SD] 223 39.1 [10.09] 231 39.6 [10.95] 234 39.7 [11.17] 190 40.8 [10.30] 193 43.3 [10.36] 195 44.3 [10.07] Change at Week 8, n Mean [SD] 223 3.9 [8.70] 231 4.1 [8.95] 234 5.0 [9.51] 190 3.1 [7.67] 193 6.1*** [8.60] 195 7.2*** [9.87] Bodily pain Baseline, n Mean [SD] 224 37.8 [8.11] 231 36.3 [7.03] 233 36.3 [7.72] 190 36.8 [7.27] 193 36.6 [8.20] 195 37.3 [7.27] Week 8, n Mean [SD] 224 40.3 [9.09] 231 40.5 [8.87] 233 41.7 [9.20] 190 40.6 [8.91] 193 43.3 [9.61] 195 45.8 [9.04] Change at Week 8, n Mean [SD] 224 2.5 [7.75] 231 4.1 [8.02] 233 5.4*** [8.07] 190 3.8 [7.31] 193 6.8** [9.47] 195 8.5*** [10.00] General health Baseline, n Mean [SD] 224 31.7 [7.59] 231 31.7 [6.70] 234 30.4 [6.89] 190 33.6 [8.69] 193 32.9 [8.45] 196 33.4 [7.47] Week 8, n Mean [SD] 224 33.2 [8.46] 231 34.0 [8.56] 234 33.4 [8.18] 190 36.3 [9.17] 193 37.8 [10.50] 196 38.9 [10.40] Change at Week 8, n Mean [SD] 224 1.6 [6.30] 231 2.4 [6.51] 234 2.9 [6.54] 190 2.7 [7.20] 193 4.8* [8.79] 196 5.6*** [9.36] Vitality Baseline, n Mean [SD] 224 35.5 [9.21] 231 35.3 [8.28] 232 34.8 [8.29] 189 36.9 [9.15] 193 36.3 [9.13] 196 37.7 [9.57] Week 8, n Mean [SD] 224 38.8 [10.05] 231 39.7 [10.49] 232 39.8 [10.19] 189 40.7 [10.95] 193 43.4 [11.82] 196 45.2 [10.91] Change at Week 8, n Mean [SD] 224 3.3 [8.12] 231 4.5 [9.43] 232 5.0* [9.05] 189 3.8 [9.17] 193 7.2** [10.46] 196 7.6*** [10.32] Social functioning Baseline, n Mean [SD] 224 35.2 [10.04] 231 35.6 [9.57] 234 34.1 [9.41] 190 36.8 [10.50] 193 36.6 [10.18] 195 36.2 [9.95] Week 8, n Mean [SD] 224 38.2 [10.97] 231 39.0 [11.03] 234 40.0 [10.63] 190 40.2 [11.36] 193 43.2 [10.79] 195 44.1 [9.86] Change at Week 8, n Mean [SD] 224 3.0 [9.24] 231 3.5 [9.76] 234 5.9** [9.50] 190 3.4 [9.55] 193 6.6** [11.04] 195 7.9*** [11.11] Role-emotional Baseline, n Mean [SD] 223 38.9 [12.51] 231 38.5 [12.17] 234 37.7 [12.48] 190 38.5 [12.39] 193 38.4 [12.86] 195 38.7 [11.97] Week 8, n Mean [SD] 223 40.7 [12.53] 231 41.9 [13.09] 234 41.5 [12.74] 190 41.3 [12.34] 193 43.7 [11.85] 195 44.8 [10.78] Change at Week 8, n Mean [SD] 223 1.9 [10.72] 231 3.4 [10.84] 234 3.8 [11.30] 190 2.8 [10.80] 193 5.3* [10.47] 195 6.1** [12.34] Mental health Baseline, n Mean [SD] 224 40.5 [10.63] 231 39.5 [10.26] 232 38.8 [9.34] 189 38.6 [11.16] 193 38.8 [10.51] 196 39.6 [11.37] Week 8, n Mean [SD] 224 42.4 [11.35] 231 42.3 [11.49] 232 43.3 [10.24] 189 41.6 [11.94] 193 44.0 [11.32] 196 45.7 [11.00] Change at Week 8, n Mean [SD] 224 1.9 [8.17] 231 2.8 [9.34] 232 4.5** [8.59] 189 3.0 [8.56] 193 5.2* [10.29] 196 6.1*** [10.91] UNITI-1 UNITI-2 Patient-reportedoutcome Ustekinumab Ustekinumab Placebo 130 mg 6 mga Placebo 130 mg 6 mga IBDQ score, nb,c 247 245 249 209 209 209 Bowel symptoms  Baseline, n  Mean [SD] 245 38.6 [9.28] 244 38.2 [8.81] 248 38.5 [8.27] 207 38.8 [9.14] 209 38.2 [9.21] 208 38.9 [9.19]  Week 8, n  Mean [SD] 245 42.6 [10.31] 244 43.7 [11.27] 248 45.1 [10.01] 207 43.9 [11.02] 209 47.5[10.96] 208 50.6 [10.88]  Change at Week 8, n  Mean [SD] 245 4.0 [8.81] 244 5.5 [9.04] 248 6.6*** [8.56] 207 5.1 [8.78] 209 9.3*** [10.76] 208 11.7*** [11.21] Emotional functions  Baseline, n  Mean [SD] 245 46.5 [13.32] 243 47.0 [13.75] 248 45.9 [11.93] 207 46.7 [14.17] 209 44.3 [13.56] 208 46.8 [14.44]  Week 8, n  Mean [SD] 245 50.7 [14.99] 243 52.8 [16.06] 248 53.7 [14.20] 207 51.2 [15.71] 209 54.5 [15.28] 208 58.6 [14.43]  Change at Week 8, n  Mean [SD] 245 4.2 [10.52] 243 5.8 [11.53] 248 7.7*** [11.82] 207 4.5 [10.79] 209 10.1*** [13.95] 208 11.9*** [14.88] Systemic symptoms Baseline, n Mean [SD] 245 15.2 [5.25] 245 14.9 [4.74] 248 14.6 [4.97] 209 15.7 [5.35] 209 15.2 [5.11] 208 15.8 [5.23] Week 8, n Mean [SD] 245 17.3 [6.09] 245 18.3 [6.52] 248 18.5 [6.60] 209 18.5 [6.46] 209 20.0 [6.61] 208 21.8 [5.94] Change at Week 8, n Mean [SD] 245 2.1 [5.10] 245 3.4* [5.65] 248 3.9*** [5.57] 209 2.8 [5.17] 209 4.8*** [6.09] 208 6.0*** [6.29] Social functions Baseline Mean [SD] 244 19.8 [7.35] 244 19.3 [7.44] 248 19.2 [7.15] 209 21.5 [7.21] 208 20.4 [7.44] 209 21.4 [7.37] Week 8 n Mean [SD] 244 21.3 [8.09] 244 22.6 [8.23] 248 23.0 [7.99] 209 23.8 [7.75] 208 25.2 [7.65] 209 26.9 [6.97] Change at Week 8, n, Mean [SD] 244 1.5 [6.03] 244 3.3** [6.14] 248 3.8*** [6.63] 209 2.3 [5.67] 208 4.8*** [6.69] 209 5.6*** [7.12] SF-36 Score, n=b,c 225 231 235 190 194 196 Physical functioning Baseline, n Mean [SD] 224 44.2 [8.52] 231 44.3 [8.61] 234 43.5 [8.70] 190 44.9 [9.57] 193 44.2 [9.38] 196 43.7 [9.13] Week 8, n Mean [SD] 224 45.9 [8.67] 231 46.7 [9.23] 234 45.9 [9.52] 190 46.6 [9.21] 193 47.9 [8.45] 196 47.9 [8.65] Change at Week 8, n Mean [SD] 224 1.7 [6.58] 231 2.4 [6.76] 234 2.4 [7.27] 190 1.8 [6.68] 193 3.7* [7.36] 196 4.2** [7.09] Role-physical Baseline, n Mean [SD] 223 35.2 [8.87] 231 35.5 [9.51] 234 34.7 [9.45] 190 37.7 [9.36] 193 37.2 [9.92] 195 37.1 [9.64] Week 8, n Mean [SD] 223 39.1 [10.09] 231 39.6 [10.95] 234 39.7 [11.17] 190 40.8 [10.30] 193 43.3 [10.36] 195 44.3 [10.07] Change at Week 8, n Mean [SD] 223 3.9 [8.70] 231 4.1 [8.95] 234 5.0 [9.51] 190 3.1 [7.67] 193 6.1*** [8.60] 195 7.2*** [9.87] Bodily pain Baseline, n Mean [SD] 224 37.8 [8.11] 231 36.3 [7.03] 233 36.3 [7.72] 190 36.8 [7.27] 193 36.6 [8.20] 195 37.3 [7.27] Week 8, n Mean [SD] 224 40.3 [9.09] 231 40.5 [8.87] 233 41.7 [9.20] 190 40.6 [8.91] 193 43.3 [9.61] 195 45.8 [9.04] Change at Week 8, n Mean [SD] 224 2.5 [7.75] 231 4.1 [8.02] 233 5.4*** [8.07] 190 3.8 [7.31] 193 6.8** [9.47] 195 8.5*** [10.00] General health Baseline, n Mean [SD] 224 31.7 [7.59] 231 31.7 [6.70] 234 30.4 [6.89] 190 33.6 [8.69] 193 32.9 [8.45] 196 33.4 [7.47] Week 8, n Mean [SD] 224 33.2 [8.46] 231 34.0 [8.56] 234 33.4 [8.18] 190 36.3 [9.17] 193 37.8 [10.50] 196 38.9 [10.40] Change at Week 8, n Mean [SD] 224 1.6 [6.30] 231 2.4 [6.51] 234 2.9 [6.54] 190 2.7 [7.20] 193 4.8* [8.79] 196 5.6*** [9.36] Vitality Baseline, n Mean [SD] 224 35.5 [9.21] 231 35.3 [8.28] 232 34.8 [8.29] 189 36.9 [9.15] 193 36.3 [9.13] 196 37.7 [9.57] Week 8, n Mean [SD] 224 38.8 [10.05] 231 39.7 [10.49] 232 39.8 [10.19] 189 40.7 [10.95] 193 43.4 [11.82] 196 45.2 [10.91] Change at Week 8, n Mean [SD] 224 3.3 [8.12] 231 4.5 [9.43] 232 5.0* [9.05] 189 3.8 [9.17] 193 7.2** [10.46] 196 7.6*** [10.32] Social functioning Baseline, n Mean [SD] 224 35.2 [10.04] 231 35.6 [9.57] 234 34.1 [9.41] 190 36.8 [10.50] 193 36.6 [10.18] 195 36.2 [9.95] Week 8, n Mean [SD] 224 38.2 [10.97] 231 39.0 [11.03] 234 40.0 [10.63] 190 40.2 [11.36] 193 43.2 [10.79] 195 44.1 [9.86] Change at Week 8, n Mean [SD] 224 3.0 [9.24] 231 3.5 [9.76] 234 5.9** [9.50] 190 3.4 [9.55] 193 6.6** [11.04] 195 7.9*** [11.11] Role-emotional Baseline, n Mean [SD] 223 38.9 [12.51] 231 38.5 [12.17] 234 37.7 [12.48] 190 38.5 [12.39] 193 38.4 [12.86] 195 38.7 [11.97] Week 8, n Mean [SD] 223 40.7 [12.53] 231 41.9 [13.09] 234 41.5 [12.74] 190 41.3 [12.34] 193 43.7 [11.85] 195 44.8 [10.78] Change at Week 8, n Mean [SD] 223 1.9 [10.72] 231 3.4 [10.84] 234 3.8 [11.30] 190 2.8 [10.80] 193 5.3* [10.47] 195 6.1** [12.34] Mental health Baseline, n Mean [SD] 224 40.5 [10.63] 231 39.5 [10.26] 232 38.8 [9.34] 189 38.6 [11.16] 193 38.8 [10.51] 196 39.6 [11.37] Week 8, n Mean [SD] 224 42.4 [11.35] 231 42.3 [11.49] 232 43.3 [10.24] 189 41.6 [11.94] 193 44.0 [11.32] 196 45.7 [11.00] Change at Week 8, n Mean [SD] 224 1.9 [8.17] 231 2.8 [9.34] 232 4.5** [8.59] 189 3.0 [8.56] 193 5.2* [10.29] 196 6.1*** [10.91] IBDQ, Inflammatory Bowel Disease Questionnaire; SD, standard deviation; SF-36, 36-Item Short Form Health Survey. aWeight-range based ustekinumab doses approximating 6 mg/kg: 260 mg [weight ≤55 kg], 390 mg [weight >55 kg and ≤85 kg], 520 mg [weight >85 kg]. bPatients who had a prohibited Crohn’s disease-related surgery or had prohibited concomitant medication changes before Week 8 had their baseline value carried forward. cPatients who had insufficient data at Week 8 had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Table 2. Mean [SD] and mean change [SD] from baseline in IBDQ domain and SF-36 scale scores at Week 8 of induction therapy. UNITI-1 UNITI-2 Patient-reportedoutcome Ustekinumab Ustekinumab Placebo 130 mg 6 mga Placebo 130 mg 6 mga IBDQ score, nb,c 247 245 249 209 209 209 Bowel symptoms  Baseline, n  Mean [SD] 245 38.6 [9.28] 244 38.2 [8.81] 248 38.5 [8.27] 207 38.8 [9.14] 209 38.2 [9.21] 208 38.9 [9.19]  Week 8, n  Mean [SD] 245 42.6 [10.31] 244 43.7 [11.27] 248 45.1 [10.01] 207 43.9 [11.02] 209 47.5[10.96] 208 50.6 [10.88]  Change at Week 8, n  Mean [SD] 245 4.0 [8.81] 244 5.5 [9.04] 248 6.6*** [8.56] 207 5.1 [8.78] 209 9.3*** [10.76] 208 11.7*** [11.21] Emotional functions  Baseline, n  Mean [SD] 245 46.5 [13.32] 243 47.0 [13.75] 248 45.9 [11.93] 207 46.7 [14.17] 209 44.3 [13.56] 208 46.8 [14.44]  Week 8, n  Mean [SD] 245 50.7 [14.99] 243 52.8 [16.06] 248 53.7 [14.20] 207 51.2 [15.71] 209 54.5 [15.28] 208 58.6 [14.43]  Change at Week 8, n  Mean [SD] 245 4.2 [10.52] 243 5.8 [11.53] 248 7.7*** [11.82] 207 4.5 [10.79] 209 10.1*** [13.95] 208 11.9*** [14.88] Systemic symptoms Baseline, n Mean [SD] 245 15.2 [5.25] 245 14.9 [4.74] 248 14.6 [4.97] 209 15.7 [5.35] 209 15.2 [5.11] 208 15.8 [5.23] Week 8, n Mean [SD] 245 17.3 [6.09] 245 18.3 [6.52] 248 18.5 [6.60] 209 18.5 [6.46] 209 20.0 [6.61] 208 21.8 [5.94] Change at Week 8, n Mean [SD] 245 2.1 [5.10] 245 3.4* [5.65] 248 3.9*** [5.57] 209 2.8 [5.17] 209 4.8*** [6.09] 208 6.0*** [6.29] Social functions Baseline Mean [SD] 244 19.8 [7.35] 244 19.3 [7.44] 248 19.2 [7.15] 209 21.5 [7.21] 208 20.4 [7.44] 209 21.4 [7.37] Week 8 n Mean [SD] 244 21.3 [8.09] 244 22.6 [8.23] 248 23.0 [7.99] 209 23.8 [7.75] 208 25.2 [7.65] 209 26.9 [6.97] Change at Week 8, n, Mean [SD] 244 1.5 [6.03] 244 3.3** [6.14] 248 3.8*** [6.63] 209 2.3 [5.67] 208 4.8*** [6.69] 209 5.6*** [7.12] SF-36 Score, n=b,c 225 231 235 190 194 196 Physical functioning Baseline, n Mean [SD] 224 44.2 [8.52] 231 44.3 [8.61] 234 43.5 [8.70] 190 44.9 [9.57] 193 44.2 [9.38] 196 43.7 [9.13] Week 8, n Mean [SD] 224 45.9 [8.67] 231 46.7 [9.23] 234 45.9 [9.52] 190 46.6 [9.21] 193 47.9 [8.45] 196 47.9 [8.65] Change at Week 8, n Mean [SD] 224 1.7 [6.58] 231 2.4 [6.76] 234 2.4 [7.27] 190 1.8 [6.68] 193 3.7* [7.36] 196 4.2** [7.09] Role-physical Baseline, n Mean [SD] 223 35.2 [8.87] 231 35.5 [9.51] 234 34.7 [9.45] 190 37.7 [9.36] 193 37.2 [9.92] 195 37.1 [9.64] Week 8, n Mean [SD] 223 39.1 [10.09] 231 39.6 [10.95] 234 39.7 [11.17] 190 40.8 [10.30] 193 43.3 [10.36] 195 44.3 [10.07] Change at Week 8, n Mean [SD] 223 3.9 [8.70] 231 4.1 [8.95] 234 5.0 [9.51] 190 3.1 [7.67] 193 6.1*** [8.60] 195 7.2*** [9.87] Bodily pain Baseline, n Mean [SD] 224 37.8 [8.11] 231 36.3 [7.03] 233 36.3 [7.72] 190 36.8 [7.27] 193 36.6 [8.20] 195 37.3 [7.27] Week 8, n Mean [SD] 224 40.3 [9.09] 231 40.5 [8.87] 233 41.7 [9.20] 190 40.6 [8.91] 193 43.3 [9.61] 195 45.8 [9.04] Change at Week 8, n Mean [SD] 224 2.5 [7.75] 231 4.1 [8.02] 233 5.4*** [8.07] 190 3.8 [7.31] 193 6.8** [9.47] 195 8.5*** [10.00] General health Baseline, n Mean [SD] 224 31.7 [7.59] 231 31.7 [6.70] 234 30.4 [6.89] 190 33.6 [8.69] 193 32.9 [8.45] 196 33.4 [7.47] Week 8, n Mean [SD] 224 33.2 [8.46] 231 34.0 [8.56] 234 33.4 [8.18] 190 36.3 [9.17] 193 37.8 [10.50] 196 38.9 [10.40] Change at Week 8, n Mean [SD] 224 1.6 [6.30] 231 2.4 [6.51] 234 2.9 [6.54] 190 2.7 [7.20] 193 4.8* [8.79] 196 5.6*** [9.36] Vitality Baseline, n Mean [SD] 224 35.5 [9.21] 231 35.3 [8.28] 232 34.8 [8.29] 189 36.9 [9.15] 193 36.3 [9.13] 196 37.7 [9.57] Week 8, n Mean [SD] 224 38.8 [10.05] 231 39.7 [10.49] 232 39.8 [10.19] 189 40.7 [10.95] 193 43.4 [11.82] 196 45.2 [10.91] Change at Week 8, n Mean [SD] 224 3.3 [8.12] 231 4.5 [9.43] 232 5.0* [9.05] 189 3.8 [9.17] 193 7.2** [10.46] 196 7.6*** [10.32] Social functioning Baseline, n Mean [SD] 224 35.2 [10.04] 231 35.6 [9.57] 234 34.1 [9.41] 190 36.8 [10.50] 193 36.6 [10.18] 195 36.2 [9.95] Week 8, n Mean [SD] 224 38.2 [10.97] 231 39.0 [11.03] 234 40.0 [10.63] 190 40.2 [11.36] 193 43.2 [10.79] 195 44.1 [9.86] Change at Week 8, n Mean [SD] 224 3.0 [9.24] 231 3.5 [9.76] 234 5.9** [9.50] 190 3.4 [9.55] 193 6.6** [11.04] 195 7.9*** [11.11] Role-emotional Baseline, n Mean [SD] 223 38.9 [12.51] 231 38.5 [12.17] 234 37.7 [12.48] 190 38.5 [12.39] 193 38.4 [12.86] 195 38.7 [11.97] Week 8, n Mean [SD] 223 40.7 [12.53] 231 41.9 [13.09] 234 41.5 [12.74] 190 41.3 [12.34] 193 43.7 [11.85] 195 44.8 [10.78] Change at Week 8, n Mean [SD] 223 1.9 [10.72] 231 3.4 [10.84] 234 3.8 [11.30] 190 2.8 [10.80] 193 5.3* [10.47] 195 6.1** [12.34] Mental health Baseline, n Mean [SD] 224 40.5 [10.63] 231 39.5 [10.26] 232 38.8 [9.34] 189 38.6 [11.16] 193 38.8 [10.51] 196 39.6 [11.37] Week 8, n Mean [SD] 224 42.4 [11.35] 231 42.3 [11.49] 232 43.3 [10.24] 189 41.6 [11.94] 193 44.0 [11.32] 196 45.7 [11.00] Change at Week 8, n Mean [SD] 224 1.9 [8.17] 231 2.8 [9.34] 232 4.5** [8.59] 189 3.0 [8.56] 193 5.2* [10.29] 196 6.1*** [10.91] UNITI-1 UNITI-2 Patient-reportedoutcome Ustekinumab Ustekinumab Placebo 130 mg 6 mga Placebo 130 mg 6 mga IBDQ score, nb,c 247 245 249 209 209 209 Bowel symptoms  Baseline, n  Mean [SD] 245 38.6 [9.28] 244 38.2 [8.81] 248 38.5 [8.27] 207 38.8 [9.14] 209 38.2 [9.21] 208 38.9 [9.19]  Week 8, n  Mean [SD] 245 42.6 [10.31] 244 43.7 [11.27] 248 45.1 [10.01] 207 43.9 [11.02] 209 47.5[10.96] 208 50.6 [10.88]  Change at Week 8, n  Mean [SD] 245 4.0 [8.81] 244 5.5 [9.04] 248 6.6*** [8.56] 207 5.1 [8.78] 209 9.3*** [10.76] 208 11.7*** [11.21] Emotional functions  Baseline, n  Mean [SD] 245 46.5 [13.32] 243 47.0 [13.75] 248 45.9 [11.93] 207 46.7 [14.17] 209 44.3 [13.56] 208 46.8 [14.44]  Week 8, n  Mean [SD] 245 50.7 [14.99] 243 52.8 [16.06] 248 53.7 [14.20] 207 51.2 [15.71] 209 54.5 [15.28] 208 58.6 [14.43]  Change at Week 8, n  Mean [SD] 245 4.2 [10.52] 243 5.8 [11.53] 248 7.7*** [11.82] 207 4.5 [10.79] 209 10.1*** [13.95] 208 11.9*** [14.88] Systemic symptoms Baseline, n Mean [SD] 245 15.2 [5.25] 245 14.9 [4.74] 248 14.6 [4.97] 209 15.7 [5.35] 209 15.2 [5.11] 208 15.8 [5.23] Week 8, n Mean [SD] 245 17.3 [6.09] 245 18.3 [6.52] 248 18.5 [6.60] 209 18.5 [6.46] 209 20.0 [6.61] 208 21.8 [5.94] Change at Week 8, n Mean [SD] 245 2.1 [5.10] 245 3.4* [5.65] 248 3.9*** [5.57] 209 2.8 [5.17] 209 4.8*** [6.09] 208 6.0*** [6.29] Social functions Baseline Mean [SD] 244 19.8 [7.35] 244 19.3 [7.44] 248 19.2 [7.15] 209 21.5 [7.21] 208 20.4 [7.44] 209 21.4 [7.37] Week 8 n Mean [SD] 244 21.3 [8.09] 244 22.6 [8.23] 248 23.0 [7.99] 209 23.8 [7.75] 208 25.2 [7.65] 209 26.9 [6.97] Change at Week 8, n, Mean [SD] 244 1.5 [6.03] 244 3.3** [6.14] 248 3.8*** [6.63] 209 2.3 [5.67] 208 4.8*** [6.69] 209 5.6*** [7.12] SF-36 Score, n=b,c 225 231 235 190 194 196 Physical functioning Baseline, n Mean [SD] 224 44.2 [8.52] 231 44.3 [8.61] 234 43.5 [8.70] 190 44.9 [9.57] 193 44.2 [9.38] 196 43.7 [9.13] Week 8, n Mean [SD] 224 45.9 [8.67] 231 46.7 [9.23] 234 45.9 [9.52] 190 46.6 [9.21] 193 47.9 [8.45] 196 47.9 [8.65] Change at Week 8, n Mean [SD] 224 1.7 [6.58] 231 2.4 [6.76] 234 2.4 [7.27] 190 1.8 [6.68] 193 3.7* [7.36] 196 4.2** [7.09] Role-physical Baseline, n Mean [SD] 223 35.2 [8.87] 231 35.5 [9.51] 234 34.7 [9.45] 190 37.7 [9.36] 193 37.2 [9.92] 195 37.1 [9.64] Week 8, n Mean [SD] 223 39.1 [10.09] 231 39.6 [10.95] 234 39.7 [11.17] 190 40.8 [10.30] 193 43.3 [10.36] 195 44.3 [10.07] Change at Week 8, n Mean [SD] 223 3.9 [8.70] 231 4.1 [8.95] 234 5.0 [9.51] 190 3.1 [7.67] 193 6.1*** [8.60] 195 7.2*** [9.87] Bodily pain Baseline, n Mean [SD] 224 37.8 [8.11] 231 36.3 [7.03] 233 36.3 [7.72] 190 36.8 [7.27] 193 36.6 [8.20] 195 37.3 [7.27] Week 8, n Mean [SD] 224 40.3 [9.09] 231 40.5 [8.87] 233 41.7 [9.20] 190 40.6 [8.91] 193 43.3 [9.61] 195 45.8 [9.04] Change at Week 8, n Mean [SD] 224 2.5 [7.75] 231 4.1 [8.02] 233 5.4*** [8.07] 190 3.8 [7.31] 193 6.8** [9.47] 195 8.5*** [10.00] General health Baseline, n Mean [SD] 224 31.7 [7.59] 231 31.7 [6.70] 234 30.4 [6.89] 190 33.6 [8.69] 193 32.9 [8.45] 196 33.4 [7.47] Week 8, n Mean [SD] 224 33.2 [8.46] 231 34.0 [8.56] 234 33.4 [8.18] 190 36.3 [9.17] 193 37.8 [10.50] 196 38.9 [10.40] Change at Week 8, n Mean [SD] 224 1.6 [6.30] 231 2.4 [6.51] 234 2.9 [6.54] 190 2.7 [7.20] 193 4.8* [8.79] 196 5.6*** [9.36] Vitality Baseline, n Mean [SD] 224 35.5 [9.21] 231 35.3 [8.28] 232 34.8 [8.29] 189 36.9 [9.15] 193 36.3 [9.13] 196 37.7 [9.57] Week 8, n Mean [SD] 224 38.8 [10.05] 231 39.7 [10.49] 232 39.8 [10.19] 189 40.7 [10.95] 193 43.4 [11.82] 196 45.2 [10.91] Change at Week 8, n Mean [SD] 224 3.3 [8.12] 231 4.5 [9.43] 232 5.0* [9.05] 189 3.8 [9.17] 193 7.2** [10.46] 196 7.6*** [10.32] Social functioning Baseline, n Mean [SD] 224 35.2 [10.04] 231 35.6 [9.57] 234 34.1 [9.41] 190 36.8 [10.50] 193 36.6 [10.18] 195 36.2 [9.95] Week 8, n Mean [SD] 224 38.2 [10.97] 231 39.0 [11.03] 234 40.0 [10.63] 190 40.2 [11.36] 193 43.2 [10.79] 195 44.1 [9.86] Change at Week 8, n Mean [SD] 224 3.0 [9.24] 231 3.5 [9.76] 234 5.9** [9.50] 190 3.4 [9.55] 193 6.6** [11.04] 195 7.9*** [11.11] Role-emotional Baseline, n Mean [SD] 223 38.9 [12.51] 231 38.5 [12.17] 234 37.7 [12.48] 190 38.5 [12.39] 193 38.4 [12.86] 195 38.7 [11.97] Week 8, n Mean [SD] 223 40.7 [12.53] 231 41.9 [13.09] 234 41.5 [12.74] 190 41.3 [12.34] 193 43.7 [11.85] 195 44.8 [10.78] Change at Week 8, n Mean [SD] 223 1.9 [10.72] 231 3.4 [10.84] 234 3.8 [11.30] 190 2.8 [10.80] 193 5.3* [10.47] 195 6.1** [12.34] Mental health Baseline, n Mean [SD] 224 40.5 [10.63] 231 39.5 [10.26] 232 38.8 [9.34] 189 38.6 [11.16] 193 38.8 [10.51] 196 39.6 [11.37] Week 8, n Mean [SD] 224 42.4 [11.35] 231 42.3 [11.49] 232 43.3 [10.24] 189 41.6 [11.94] 193 44.0 [11.32] 196 45.7 [11.00] Change at Week 8, n Mean [SD] 224 1.9 [8.17] 231 2.8 [9.34] 232 4.5** [8.59] 189 3.0 [8.56] 193 5.2* [10.29] 196 6.1*** [10.91] IBDQ, Inflammatory Bowel Disease Questionnaire; SD, standard deviation; SF-36, 36-Item Short Form Health Survey. aWeight-range based ustekinumab doses approximating 6 mg/kg: 260 mg [weight ≤55 kg], 390 mg [weight >55 kg and ≤85 kg], 520 mg [weight >85 kg]. bPatients who had a prohibited Crohn’s disease-related surgery or had prohibited concomitant medication changes before Week 8 had their baseline value carried forward. cPatients who had insufficient data at Week 8 had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large With both ustekinumab doses in both studies, significantly greater proportions of patients experienced clinically meaningful improvement in IBDQ at Week 8 [UNITI-1: 54.8% and 46.9%, respectively, versus 36.5%; p <0.001 and p = 0.019, respectively; UNITI-2: 68.1% and 58.7%, respectively, versus 41.1%; p <0.001 and p <0.001, respectively; Figure 2A, B]. All patients had impaired baseline IBDQ scores [<210 points]. In both ustekinumab dose groups at Week 8, a greater proportion of patients had normal scores [≥210 points] than placebo [Figure 2A, B]. In UNITI-2, this comparison was only statistically significant for the comparison of ustekinumab 6 mg/kg with placebo [5.8% versus 1.4%, p = 0.019]. 3.1.2. SF-36 results In both studies, the mean baseline SF-36, PCS, and MCS scores were similar among the three treatment groups [Table 1; Figure 1C-F]. In UNITI-1 at Week 8, the mean change from baseline in the PCS score was numerically, but not significantly, greater in the both ustekinumab dose groups compared with the placebo group. The mean change from baseline in the MCS score at that time was significantly greater in the ustekinumab 6 mg/kg group [p = 0.006], but only numerically greater for the ustekinumab 130 mg group compared with the placebo group. In UNITI-2, the mean changes from baseline in the MCS and PCS scores were significantly greater for both ustekinumab groups compared with the placebo group [p <0.05 for all comparisons; Table 1]. In UNITI-1, mean changes from baseline in norm-based scores of the SF-36 scales at Week 8 were numerically greater in both ustekinumab groups compared with placebo; however, the ustekinumab 6 mg/kg group showed relatively greater differences, with statistically significant differences observed for bodily pain, vitality, social functioning, and mental health scales [Table 2]. In UNITI-2, the mean changes from baseline in norm-based scores of the SF-36 scales at Week 8 were significantly greater in both ustekinumab groups compared with the placebo group [p <0.05 for all comparisons; Table 2]. In UNITI-2, the proportion of patients with a clinically meaningful improvement in PCS was significantly greater for the ustekinumab 6 mg/kg and 130 mg groups than for the placebo group [49.2% and 44.0%, respectively versus 31.2%; p <0.001 and p = 0.009, respectively]. More patients experienced clinically significant improvement in MCS in both the ustekinumab 6 mg/kg and 130 mg groups than the placebo group [51.3% and 49.2%, respectively, versus 38.6%; p = 0.014 and p = 0.036, respectively]. In UNITI-1, MCS scores were only significantly greater for the ustekinumab 6 mg/kg group in comparison with the placebo group [42.4% versus 30.0%; p = 0.007] [Figure 2A, B]. For patients with impaired SF-36 scores at baseline, defined as less than the US population norm of 50 points, greater proportions of patients receiving either ustekinumab dose had normal MCS and PCS scores compared with placebo at Week 8 [Figure 2A, B]. These differences were statistically significant in UNITI-2 for the MCS [with both ustekinumab doses] and for the PCS in the ustekinumab 6 mg/kg group. Figure 2. View largeDownload slide Proportions of patients at Week 8 who achieved ≥16-point improvement in or normalised [≥210] IBDQ total scores and proportions of patients who achieved ≥5-point improvement in or normalized [≥50] SF-36 MCS and PCS scores with induction therapy. IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, Mental Component Summary Score; NS, not statistically significant; PCS, Physical Component Summary Score; SF-36, 36-item Short Form Health Survey. Figure 2. View largeDownload slide Proportions of patients at Week 8 who achieved ≥16-point improvement in or normalised [≥210] IBDQ total scores and proportions of patients who achieved ≥5-point improvement in or normalized [≥50] SF-36 MCS and PCS scores with induction therapy. IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, Mental Component Summary Score; NS, not statistically significant; PCS, Physical Component Summary Score; SF-36, 36-item Short Form Health Survey. 3.2. Maintenance study 3.2.1. IBDQ results At baseline of the maintenance study [induction Week 8], the mean [SD] IBDQ scores for randomised ustekinumab responders were generally similar among the placebo and ustekinumab q12w and q8w groups (163.6 [31.75], 165.8 [32.82], and 170.5 [29.33], respectively) [Table 3; Figure 3A]. At Week 20, the mean decrease [worsening] in IBDQ score from maintenance baseline was significantly less in the ustekinumab 90 mg q12w group and numerically less in the ustekinumab q8w dose group compared with the placebo group [p = 0.035 and p = 0.183, respectively; Table 3]. At Week 44, the mean decreases in IBDQ scores from maintenance baseline were significantly less in the ustekinumab q12w and q8w dose groups (-8.9 [43.08] versus -9.9 [34.83], respectively) compared with the placebo group (-21.5 [39.26]; p < 0.001 and p = 0.003, respectively; Table 3; Figure 3A]. These results indicate that patients who received ustekinumab were more likely to maintain the improvement in their IBDQ scores achieved during induction compared with patients who discontinued ustekinumab treatment. Table 3. Mean [SD] and mean change [SD] from baseline in the IBDQ score at Week 20 and Week 44 of maintenance therapy. Ustekinumab Placebo SCa [n = 131] 90 mg SC q12w [n = 129] 90 mg SC q8w [n = 128] Baseline, n 130 129 126  Mean [SD] 163.6 [31.76] 165.8 [32.82] 170.5 [29.33] Week 20, n 130 129 126  Mean [SD] 150.8 [40.99] 159.6 [40.96] 161.6 [40.27] Change from baseline Week 20b,c, n 130 129 126  Mean [SD] -12.8 [34.05] -6.3 [37.04]* -8.9 [31.46] Week 44, n 130 128 126  Mean [SD] 142.1 [42.46] 156.9 [43.54] 160.5 [40.71] Change from baseline Week 44b,c, n 130 128 126  Mean [SD] -21.5 [39.26] -8.9 [43.08]*** -9.9 [34.83]** Ustekinumab Placebo SCa [n = 131] 90 mg SC q12w [n = 129] 90 mg SC q8w [n = 128] Baseline, n 130 129 126  Mean [SD] 163.6 [31.76] 165.8 [32.82] 170.5 [29.33] Week 20, n 130 129 126  Mean [SD] 150.8 [40.99] 159.6 [40.96] 161.6 [40.27] Change from baseline Week 20b,c, n 130 129 126  Mean [SD] -12.8 [34.05] -6.3 [37.04]* -8.9 [31.46] Week 44, n 130 128 126  Mean [SD] 142.1 [42.46] 156.9 [43.54] 160.5 [40.71] Change from baseline Week 44b,c, n 130 128 126  Mean [SD] -21.5 [39.26] -8.9 [43.08]*** -9.9 [34.83]** IBDQ, inflammatory bowel disease questionnaire; IV, intravenous; SC, subcutaneous; SD, standard deviation; q8w, every 8 weeks; q12w, every 12 weeks. aPatients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study. bPatients who had a prohibited Crohn’s disease-related surgery, had a loss of response, had prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be worsened Crohn’s disease before the designated analysis timepoint had their induction baseline value carried forward. cPatients who had insufficient data at the designated analysis timepoint had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Table 3. Mean [SD] and mean change [SD] from baseline in the IBDQ score at Week 20 and Week 44 of maintenance therapy. Ustekinumab Placebo SCa [n = 131] 90 mg SC q12w [n = 129] 90 mg SC q8w [n = 128] Baseline, n 130 129 126  Mean [SD] 163.6 [31.76] 165.8 [32.82] 170.5 [29.33] Week 20, n 130 129 126  Mean [SD] 150.8 [40.99] 159.6 [40.96] 161.6 [40.27] Change from baseline Week 20b,c, n 130 129 126  Mean [SD] -12.8 [34.05] -6.3 [37.04]* -8.9 [31.46] Week 44, n 130 128 126  Mean [SD] 142.1 [42.46] 156.9 [43.54] 160.5 [40.71] Change from baseline Week 44b,c, n 130 128 126  Mean [SD] -21.5 [39.26] -8.9 [43.08]*** -9.9 [34.83]** Ustekinumab Placebo SCa [n = 131] 90 mg SC q12w [n = 129] 90 mg SC q8w [n = 128] Baseline, n 130 129 126  Mean [SD] 163.6 [31.76] 165.8 [32.82] 170.5 [29.33] Week 20, n 130 129 126  Mean [SD] 150.8 [40.99] 159.6 [40.96] 161.6 [40.27] Change from baseline Week 20b,c, n 130 129 126  Mean [SD] -12.8 [34.05] -6.3 [37.04]* -8.9 [31.46] Week 44, n 130 128 126  Mean [SD] 142.1 [42.46] 156.9 [43.54] 160.5 [40.71] Change from baseline Week 44b,c, n 130 128 126  Mean [SD] -21.5 [39.26] -8.9 [43.08]*** -9.9 [34.83]** IBDQ, inflammatory bowel disease questionnaire; IV, intravenous; SC, subcutaneous; SD, standard deviation; q8w, every 8 weeks; q12w, every 12 weeks. aPatients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study. bPatients who had a prohibited Crohn’s disease-related surgery, had a loss of response, had prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be worsened Crohn’s disease before the designated analysis timepoint had their induction baseline value carried forward. cPatients who had insufficient data at the designated analysis timepoint had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Figure 3. View largeDownload slide Mean and mean change from baseline, Week 20, and Week 44 in IBDQ [A], PCS [B] and MCS [C] scores with maintenance therapy. Figure 3. View largeDownload slide Mean and mean change from baseline, Week 20, and Week 44 in IBDQ [A], PCS [B] and MCS [C] scores with maintenance therapy. The proportion of patients with a clinically meaningful improvement in IBDQ score at Week 44 was significantly greater than placebo for the ustekinumab q8w dose but not for the ustekinumab q12w dose group [67.9% and 61.3%, respectively, versus placebo 50.4%; p = 0.014 and p = 0.140, respectively; Figure 4]. Among patients with IBDQ scores of <210 points at baseline of an induction study, greater proportions of patients receiving either ustekinumab dose, than placebo, achieved normal scores at Week 44 following maintenance treatment [Figure 4]. Figure 4. View largeDownload slide Proportions of patients at Week 44 who achieved ≥16-point improvement in or normalised [≥210] IBDQ total score and proportions of patients who achieved ≥5-point improvement in or normalised [≥50] SF-36 PCS and MCS scores from the baseline of an induction study. IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, Mental Component Summary Score; NS, not statistically significant; PCS, Physical Component Summary Score; q8w, every 8 weeks; q12w, every 12 weeks. SF-36, 36-item Short Form Health Survey. Figure 4. View largeDownload slide Proportions of patients at Week 44 who achieved ≥16-point improvement in or normalised [≥210] IBDQ total score and proportions of patients who achieved ≥5-point improvement in or normalised [≥50] SF-36 PCS and MCS scores from the baseline of an induction study. IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, Mental Component Summary Score; NS, not statistically significant; PCS, Physical Component Summary Score; q8w, every 8 weeks; q12w, every 12 weeks. SF-36, 36-item Short Form Health Survey. 3.2.2. SF-36 results The mean PCS and MCS scores of the SF-36 at baseline of maintenance [induction Week 8] were similar among the three treatment groups [Table 4; Figure 3B, C]. For the ustekinumab q8w group, the mean decreases from baseline [worsening] of the maintenance study in the PCS and MCS scores were significantly less at Week 44 compared with the placebo group [Table 4]. For the ustekinumab q12w group, only the mean decrease from baseline during maintenance in the MCS score at Week 44 was significantly less compared with the placebo group. Table 4. Mean [SD] and mean change [SD] from baseline in the physical and mental component summary scores of the SF-36 at Week 20 and Week 44 of maintenance therapy. Ustekinumab SF-36 Component Summary Scores Placebo SCa [n = 122] 90 mg SC q12w [n= 121] 90 mg SC q8w [n= 121] Physical Component Summary Baseline, n 122 121 121  Mean [SD] 46.3 [8.21] 47.1 [8.10] 47.4 [7.52] Week 20b,c, n 122 121 121  Mean [SD] 44.6 [9.71] 45.4 [8.86] 46.8 [9.08] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -1.7 [7.67] -1.7 [7.18] -0.6 [6.37] Week 44b,c, n 122 120 121  Mean [SD] 42.7 [9.96] 44.9 [9.62] 46.5 [8.98] Change from baseline Week 44b,c, n 122 120 121  Mean [SD] -3.6 [9.33] -2.3 [9.31] -0.9 [7.14]** Mental component summary Baseline, n 122 121 121  Mean [SD] 45.7 [10.89] 46.4 [10.66] 47.3 [9.91] Week 20b,c, n 122 121 121  Mean [SD] 43.0 [11.34] 45.1 [11.40] 45.6 [10.57] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -2.7 [10.78] -1.3 [11.53] -1.7 [9.01] Week 44b,c, n 122 120 121  Mean [SD] 41.3 [11.79] 44.6 [11.81] 45.6 [11.22] Change from baseline Week 44b,c., n 122 120 121  Mean [SD] -4.4 [11.06] -1.9 [12.68]* -1.7 [9.76]** Ustekinumab SF-36 Component Summary Scores Placebo SCa [n = 122] 90 mg SC q12w [n= 121] 90 mg SC q8w [n= 121] Physical Component Summary Baseline, n 122 121 121  Mean [SD] 46.3 [8.21] 47.1 [8.10] 47.4 [7.52] Week 20b,c, n 122 121 121  Mean [SD] 44.6 [9.71] 45.4 [8.86] 46.8 [9.08] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -1.7 [7.67] -1.7 [7.18] -0.6 [6.37] Week 44b,c, n 122 120 121  Mean [SD] 42.7 [9.96] 44.9 [9.62] 46.5 [8.98] Change from baseline Week 44b,c, n 122 120 121  Mean [SD] -3.6 [9.33] -2.3 [9.31] -0.9 [7.14]** Mental component summary Baseline, n 122 121 121  Mean [SD] 45.7 [10.89] 46.4 [10.66] 47.3 [9.91] Week 20b,c, n 122 121 121  Mean [SD] 43.0 [11.34] 45.1 [11.40] 45.6 [10.57] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -2.7 [10.78] -1.3 [11.53] -1.7 [9.01] Week 44b,c, n 122 120 121  Mean [SD] 41.3 [11.79] 44.6 [11.81] 45.6 [11.22] Change from baseline Week 44b,c., n 122 120 121  Mean [SD] -4.4 [11.06] -1.9 [12.68]* -1.7 [9.76]** IV, intravenous; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous; SD, standard deviation; SF-36, 36-item Short-Form Health Survey. aPatients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study. bPatients who had a prohibited Crohn’s disease-related surgery, had a loss of response, had prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be worsened Crohn’s disease before the designated analysis timepoint had their induction baseline value carried forward. cPatients who had insufficient data at the designated analysis timepoint had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Table 4. Mean [SD] and mean change [SD] from baseline in the physical and mental component summary scores of the SF-36 at Week 20 and Week 44 of maintenance therapy. Ustekinumab SF-36 Component Summary Scores Placebo SCa [n = 122] 90 mg SC q12w [n= 121] 90 mg SC q8w [n= 121] Physical Component Summary Baseline, n 122 121 121  Mean [SD] 46.3 [8.21] 47.1 [8.10] 47.4 [7.52] Week 20b,c, n 122 121 121  Mean [SD] 44.6 [9.71] 45.4 [8.86] 46.8 [9.08] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -1.7 [7.67] -1.7 [7.18] -0.6 [6.37] Week 44b,c, n 122 120 121  Mean [SD] 42.7 [9.96] 44.9 [9.62] 46.5 [8.98] Change from baseline Week 44b,c, n 122 120 121  Mean [SD] -3.6 [9.33] -2.3 [9.31] -0.9 [7.14]** Mental component summary Baseline, n 122 121 121  Mean [SD] 45.7 [10.89] 46.4 [10.66] 47.3 [9.91] Week 20b,c, n 122 121 121  Mean [SD] 43.0 [11.34] 45.1 [11.40] 45.6 [10.57] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -2.7 [10.78] -1.3 [11.53] -1.7 [9.01] Week 44b,c, n 122 120 121  Mean [SD] 41.3 [11.79] 44.6 [11.81] 45.6 [11.22] Change from baseline Week 44b,c., n 122 120 121  Mean [SD] -4.4 [11.06] -1.9 [12.68]* -1.7 [9.76]** Ustekinumab SF-36 Component Summary Scores Placebo SCa [n = 122] 90 mg SC q12w [n= 121] 90 mg SC q8w [n= 121] Physical Component Summary Baseline, n 122 121 121  Mean [SD] 46.3 [8.21] 47.1 [8.10] 47.4 [7.52] Week 20b,c, n 122 121 121  Mean [SD] 44.6 [9.71] 45.4 [8.86] 46.8 [9.08] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -1.7 [7.67] -1.7 [7.18] -0.6 [6.37] Week 44b,c, n 122 120 121  Mean [SD] 42.7 [9.96] 44.9 [9.62] 46.5 [8.98] Change from baseline Week 44b,c, n 122 120 121  Mean [SD] -3.6 [9.33] -2.3 [9.31] -0.9 [7.14]** Mental component summary Baseline, n 122 121 121  Mean [SD] 45.7 [10.89] 46.4 [10.66] 47.3 [9.91] Week 20b,c, n 122 121 121  Mean [SD] 43.0 [11.34] 45.1 [11.40] 45.6 [10.57] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -2.7 [10.78] -1.3 [11.53] -1.7 [9.01] Week 44b,c, n 122 120 121  Mean [SD] 41.3 [11.79] 44.6 [11.81] 45.6 [11.22] Change from baseline Week 44b,c., n 122 120 121  Mean [SD] -4.4 [11.06] -1.9 [12.68]* -1.7 [9.76]** IV, intravenous; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous; SD, standard deviation; SF-36, 36-item Short-Form Health Survey. aPatients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study. bPatients who had a prohibited Crohn’s disease-related surgery, had a loss of response, had prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be worsened Crohn’s disease before the designated analysis timepoint had their induction baseline value carried forward. cPatients who had insufficient data at the designated analysis timepoint had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large For the SF-36 PCS and MCS scores, both the ustekinumab q8w and q12w dose groups had significantly greater proportions of patients with a clinically meaningful [≥5-point] improvement, except for the PCS in the ustekinumab q12w group [Figure 4]. A significantly greater proportion of patients in the ustekinumab q8w group achieved clinically-meaningful improvement in PCS than in the placebo group [52.1% versus placebo, 34.7%; p = 0.008], and a significantly greater proportion of patients in the ustekinumab q8w and q12w dose groups achieved a clinically meaningful improvement in MCS than the placebo group at Week 44 [47.9% and 46.7%, respectively, versus placebo, 28.9%; p = 0.003 and p = 0.005, respectively; Figure 4]. For patients with baseline SF-36 scores lower than the US population norm, greater proportions of patients in both ustekinumab dose groups had normal MCS and PCS scores at Week 44 [Figure 4]. These results were significantly greater with ustekinumab q8w for both MCS and PCS. The mean SF-36 dimension scores [i.e. physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health] were generally consistent across all groups at baseline of the maintenance study. At Week 44, the mean worsening from baseline in the SF-36 dimension scores was generally less in the ustekinumab q12w and q8w groups compared with the placebo group [Table 5]. Specifically, the mean decreases [worsening] in general health, vitality, and mental health dimension scores in the ustekinumab q12w group were significantly less than those observed in the placebo group at Week 44, whereas the mean worsening in six of the eight dimension scores [physical functioning, role-physical, bodily pain, vitality, social functioning, and mental health] in the ustekinumab q8w group were significantly less than those observed for the placebo group at Week 44. Table 5. Mean [SD] and mean change [SD] from baseline in IBDQ and SF-36 dimension and scale scores at Week 44 of maintenance therapy. Ustekinumab Patient-reported outcome Placebo SCa 90 mg SC q12w 90 mg SC q8w IBDQb,c 131 129 128 Bowel symptoms Baseline, n Mean [SD] 131 52.2 [9.86] 129 53.7 [8.93] 128 54.0 [8.92] Week 44, n Mean [SD] 131 45.5 [12.70] 128 50.4 [13.48] 127 51.4 [12.63] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.7 [11.62] -3.3** [12.26] -3.0*** [11.06] Emotional functions Baseline, n Mean [SD] 131 60.4 [13.39] 129 61.1 [14.52] 127 62.8 [12.44] Week 44, n Mean [SD] 131 53.8 [16.26] 128 58.6 [17.05] 127 59.9 [15.99] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.6 [15.76] -2.6** [17.46] -2.9** [13.42] Systemic symptoms Baseline, n Mean [SD] 130 23.1 [5.79] 129 23.2 [6.04] 128 23.9 [5.55] Week 44, n Mean [SD] 130 18.9 [7.78] 128 20.9 [7.41] 128 21.9 [7.14] Change from baseline Week 44, n 130 128 128 Mean [SD] -4.2 [7.42] -2.3* [7.77] -2.0** [6.19] Social functions Baseline, n Mean [SD] 131 27.8 [6.31] 129 27.9 [7.18] 127 28.8 [6.25] Week 44, n Mean [SD] 131 24.1 [8.98] 128 27.1 [8.20] 127 27.0 [7.80] Change from baseline Week 44, n 131 128 127 Mean [SD] -3.7 [7.67] -0.8*** [8.49] -1.8* [7.38] SF-36b,c 122 121 121 Physical functioning Baseline, n Mean [SD] 122 49.8 [7.70] 121 50.4 [8.51] 121 51.0 [7.33] Week 44, n Mean [SD] 122 46.7 [9.35] 121 48.5 [9.67] 121 50.6 [7.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.2 [8.42] -1.9 [7.94] -0.4** [5.63] Role-physical Baseline, n Mean [SD] 122 45.6 [9.75] 121 46.3 [9.93] 121 47.6 [9.37] Week 44, n Mean [SD] 122 40.8 [12.01] 121 43.4 [11.89] 121 46.0 [10.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.8 [11.87] -2.9 [12.73] -1.6** [8.79] Bodily pain Baseline, n Mean [SD] 122 47.1 [8.04] 121 48.8 [8.17] 121 48.2 [8.67] Week 44, n Mean [SD] 122 42.1 [10.65] 120 45.1 [11.34] 121 46.5 [10.97] Change from baseline Week 44, n 122 120 121 Mean [SD] -5.0 [10.61] -3.8 [11.73] -1.7** [8.87] General health Baseline, n Mean [SD] 122 39.5 [10.37] 121 40.0 [10.54] 121 40.7 [10.06] Week 44, n Mean [SD] 122 37.2 [10.94] 121 39.9 [11.31] 121 40.1 [11.03] Change from baseline Week 44, n 122 121 121 Mean [SD] -2.3 [10.18] -0.1* [10.25] -0.6 [8.78] Vitality Baseline, n Mean [SD]Week 44, n Mean [SD]Change from baseline Week 44, nMean [SD] 122 46.4 [10.27]122 41.4 [12.25]122-5.0 [11.77] 121 47.2 [10.82]120 44.8 [12.83]120-2.4* [12.42] 121 48.6 [10.94]121 45.6 [12.45]121-2.9* [10.38] Social functioning Baseline, n Mean [SD] 122 45.7 [8.89] 121 46.4 [10.17] 121 46.5 [9.54] Week 44, n Mean [SD] 122 41.5 [11.79] 121 44.1 [11.76] 121 45.3 [10.96] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.2 [12.23] -2.3 [13.41] -1.2* [10.06] Role-emotional Baseline, n Mean [SD] 122 45.5 [11.95] 121 46.4 [10.90] 121 47.9 [9.64] Week 44, n Mean [SD] 122 42.2 [13.46] 121 44.6 [12.80] 121 46.5 [11.69] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.3 [11.59] -1.8 [14.04] -1.4 [9.29] Mental health Baseline, n Mean [SD] 122 46.9 [10.68] 121 47.7 [10.11] 121 48.1 [10.30] Week 44, n Mean [SD] 122 42.0 [10.98] 120 45.6 [11.57] 121 47.0 [10.81] Change from baseline Week 44, n 122 120 121 Mean [SD] -4.9 [10.52] -2.3** [11.93] -1.1*** [9.85] Ustekinumab Patient-reported outcome Placebo SCa 90 mg SC q12w 90 mg SC q8w IBDQb,c 131 129 128 Bowel symptoms Baseline, n Mean [SD] 131 52.2 [9.86] 129 53.7 [8.93] 128 54.0 [8.92] Week 44, n Mean [SD] 131 45.5 [12.70] 128 50.4 [13.48] 127 51.4 [12.63] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.7 [11.62] -3.3** [12.26] -3.0*** [11.06] Emotional functions Baseline, n Mean [SD] 131 60.4 [13.39] 129 61.1 [14.52] 127 62.8 [12.44] Week 44, n Mean [SD] 131 53.8 [16.26] 128 58.6 [17.05] 127 59.9 [15.99] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.6 [15.76] -2.6** [17.46] -2.9** [13.42] Systemic symptoms Baseline, n Mean [SD] 130 23.1 [5.79] 129 23.2 [6.04] 128 23.9 [5.55] Week 44, n Mean [SD] 130 18.9 [7.78] 128 20.9 [7.41] 128 21.9 [7.14] Change from baseline Week 44, n 130 128 128 Mean [SD] -4.2 [7.42] -2.3* [7.77] -2.0** [6.19] Social functions Baseline, n Mean [SD] 131 27.8 [6.31] 129 27.9 [7.18] 127 28.8 [6.25] Week 44, n Mean [SD] 131 24.1 [8.98] 128 27.1 [8.20] 127 27.0 [7.80] Change from baseline Week 44, n 131 128 127 Mean [SD] -3.7 [7.67] -0.8*** [8.49] -1.8* [7.38] SF-36b,c 122 121 121 Physical functioning Baseline, n Mean [SD] 122 49.8 [7.70] 121 50.4 [8.51] 121 51.0 [7.33] Week 44, n Mean [SD] 122 46.7 [9.35] 121 48.5 [9.67] 121 50.6 [7.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.2 [8.42] -1.9 [7.94] -0.4** [5.63] Role-physical Baseline, n Mean [SD] 122 45.6 [9.75] 121 46.3 [9.93] 121 47.6 [9.37] Week 44, n Mean [SD] 122 40.8 [12.01] 121 43.4 [11.89] 121 46.0 [10.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.8 [11.87] -2.9 [12.73] -1.6** [8.79] Bodily pain Baseline, n Mean [SD] 122 47.1 [8.04] 121 48.8 [8.17] 121 48.2 [8.67] Week 44, n Mean [SD] 122 42.1 [10.65] 120 45.1 [11.34] 121 46.5 [10.97] Change from baseline Week 44, n 122 120 121 Mean [SD] -5.0 [10.61] -3.8 [11.73] -1.7** [8.87] General health Baseline, n Mean [SD] 122 39.5 [10.37] 121 40.0 [10.54] 121 40.7 [10.06] Week 44, n Mean [SD] 122 37.2 [10.94] 121 39.9 [11.31] 121 40.1 [11.03] Change from baseline Week 44, n 122 121 121 Mean [SD] -2.3 [10.18] -0.1* [10.25] -0.6 [8.78] Vitality Baseline, n Mean [SD]Week 44, n Mean [SD]Change from baseline Week 44, nMean [SD] 122 46.4 [10.27]122 41.4 [12.25]122-5.0 [11.77] 121 47.2 [10.82]120 44.8 [12.83]120-2.4* [12.42] 121 48.6 [10.94]121 45.6 [12.45]121-2.9* [10.38] Social functioning Baseline, n Mean [SD] 122 45.7 [8.89] 121 46.4 [10.17] 121 46.5 [9.54] Week 44, n Mean [SD] 122 41.5 [11.79] 121 44.1 [11.76] 121 45.3 [10.96] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.2 [12.23] -2.3 [13.41] -1.2* [10.06] Role-emotional Baseline, n Mean [SD] 122 45.5 [11.95] 121 46.4 [10.90] 121 47.9 [9.64] Week 44, n Mean [SD] 122 42.2 [13.46] 121 44.6 [12.80] 121 46.5 [11.69] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.3 [11.59] -1.8 [14.04] -1.4 [9.29] Mental health Baseline, n Mean [SD] 122 46.9 [10.68] 121 47.7 [10.11] 121 48.1 [10.30] Week 44, n Mean [SD] 122 42.0 [10.98] 120 45.6 [11.57] 121 47.0 [10.81] Change from baseline Week 44, n 122 120 121 Mean [SD] -4.9 [10.52] -2.3** [11.93] -1.1*** [9.85] IBDQ, Inflammatory Bowel Disease Questionnaire; IV, intravenous; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous; SD, standard deviation; SF-36, 36-Item Short Form Health Survey. aPatients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study. bPatients who had a prohibited Crohn’s disease-related surgery, had a loss of response, had prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be worsened Crohn’s disease before the designated analysis timepoint had their induction baseline value carried forward. cPatients who had insufficient data at the designated analysis timepoint had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Table 5. Mean [SD] and mean change [SD] from baseline in IBDQ and SF-36 dimension and scale scores at Week 44 of maintenance therapy. Ustekinumab Patient-reported outcome Placebo SCa 90 mg SC q12w 90 mg SC q8w IBDQb,c 131 129 128 Bowel symptoms Baseline, n Mean [SD] 131 52.2 [9.86] 129 53.7 [8.93] 128 54.0 [8.92] Week 44, n Mean [SD] 131 45.5 [12.70] 128 50.4 [13.48] 127 51.4 [12.63] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.7 [11.62] -3.3** [12.26] -3.0*** [11.06] Emotional functions Baseline, n Mean [SD] 131 60.4 [13.39] 129 61.1 [14.52] 127 62.8 [12.44] Week 44, n Mean [SD] 131 53.8 [16.26] 128 58.6 [17.05] 127 59.9 [15.99] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.6 [15.76] -2.6** [17.46] -2.9** [13.42] Systemic symptoms Baseline, n Mean [SD] 130 23.1 [5.79] 129 23.2 [6.04] 128 23.9 [5.55] Week 44, n Mean [SD] 130 18.9 [7.78] 128 20.9 [7.41] 128 21.9 [7.14] Change from baseline Week 44, n 130 128 128 Mean [SD] -4.2 [7.42] -2.3* [7.77] -2.0** [6.19] Social functions Baseline, n Mean [SD] 131 27.8 [6.31] 129 27.9 [7.18] 127 28.8 [6.25] Week 44, n Mean [SD] 131 24.1 [8.98] 128 27.1 [8.20] 127 27.0 [7.80] Change from baseline Week 44, n 131 128 127 Mean [SD] -3.7 [7.67] -0.8*** [8.49] -1.8* [7.38] SF-36b,c 122 121 121 Physical functioning Baseline, n Mean [SD] 122 49.8 [7.70] 121 50.4 [8.51] 121 51.0 [7.33] Week 44, n Mean [SD] 122 46.7 [9.35] 121 48.5 [9.67] 121 50.6 [7.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.2 [8.42] -1.9 [7.94] -0.4** [5.63] Role-physical Baseline, n Mean [SD] 122 45.6 [9.75] 121 46.3 [9.93] 121 47.6 [9.37] Week 44, n Mean [SD] 122 40.8 [12.01] 121 43.4 [11.89] 121 46.0 [10.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.8 [11.87] -2.9 [12.73] -1.6** [8.79] Bodily pain Baseline, n Mean [SD] 122 47.1 [8.04] 121 48.8 [8.17] 121 48.2 [8.67] Week 44, n Mean [SD] 122 42.1 [10.65] 120 45.1 [11.34] 121 46.5 [10.97] Change from baseline Week 44, n 122 120 121 Mean [SD] -5.0 [10.61] -3.8 [11.73] -1.7** [8.87] General health Baseline, n Mean [SD] 122 39.5 [10.37] 121 40.0 [10.54] 121 40.7 [10.06] Week 44, n Mean [SD] 122 37.2 [10.94] 121 39.9 [11.31] 121 40.1 [11.03] Change from baseline Week 44, n 122 121 121 Mean [SD] -2.3 [10.18] -0.1* [10.25] -0.6 [8.78] Vitality Baseline, n Mean [SD]Week 44, n Mean [SD]Change from baseline Week 44, nMean [SD] 122 46.4 [10.27]122 41.4 [12.25]122-5.0 [11.77] 121 47.2 [10.82]120 44.8 [12.83]120-2.4* [12.42] 121 48.6 [10.94]121 45.6 [12.45]121-2.9* [10.38] Social functioning Baseline, n Mean [SD] 122 45.7 [8.89] 121 46.4 [10.17] 121 46.5 [9.54] Week 44, n Mean [SD] 122 41.5 [11.79] 121 44.1 [11.76] 121 45.3 [10.96] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.2 [12.23] -2.3 [13.41] -1.2* [10.06] Role-emotional Baseline, n Mean [SD] 122 45.5 [11.95] 121 46.4 [10.90] 121 47.9 [9.64] Week 44, n Mean [SD] 122 42.2 [13.46] 121 44.6 [12.80] 121 46.5 [11.69] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.3 [11.59] -1.8 [14.04] -1.4 [9.29] Mental health Baseline, n Mean [SD] 122 46.9 [10.68] 121 47.7 [10.11] 121 48.1 [10.30] Week 44, n Mean [SD] 122 42.0 [10.98] 120 45.6 [11.57] 121 47.0 [10.81] Change from baseline Week 44, n 122 120 121 Mean [SD] -4.9 [10.52] -2.3** [11.93] -1.1*** [9.85] Ustekinumab Patient-reported outcome Placebo SCa 90 mg SC q12w 90 mg SC q8w IBDQb,c 131 129 128 Bowel symptoms Baseline, n Mean [SD] 131 52.2 [9.86] 129 53.7 [8.93] 128 54.0 [8.92] Week 44, n Mean [SD] 131 45.5 [12.70] 128 50.4 [13.48] 127 51.4 [12.63] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.7 [11.62] -3.3** [12.26] -3.0*** [11.06] Emotional functions Baseline, n Mean [SD] 131 60.4 [13.39] 129 61.1 [14.52] 127 62.8 [12.44] Week 44, n Mean [SD] 131 53.8 [16.26] 128 58.6 [17.05] 127 59.9 [15.99] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.6 [15.76] -2.6** [17.46] -2.9** [13.42] Systemic symptoms Baseline, n Mean [SD] 130 23.1 [5.79] 129 23.2 [6.04] 128 23.9 [5.55] Week 44, n Mean [SD] 130 18.9 [7.78] 128 20.9 [7.41] 128 21.9 [7.14] Change from baseline Week 44, n 130 128 128 Mean [SD] -4.2 [7.42] -2.3* [7.77] -2.0** [6.19] Social functions Baseline, n Mean [SD] 131 27.8 [6.31] 129 27.9 [7.18] 127 28.8 [6.25] Week 44, n Mean [SD] 131 24.1 [8.98] 128 27.1 [8.20] 127 27.0 [7.80] Change from baseline Week 44, n 131 128 127 Mean [SD] -3.7 [7.67] -0.8*** [8.49] -1.8* [7.38] SF-36b,c 122 121 121 Physical functioning Baseline, n Mean [SD] 122 49.8 [7.70] 121 50.4 [8.51] 121 51.0 [7.33] Week 44, n Mean [SD] 122 46.7 [9.35] 121 48.5 [9.67] 121 50.6 [7.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.2 [8.42] -1.9 [7.94] -0.4** [5.63] Role-physical Baseline, n Mean [SD] 122 45.6 [9.75] 121 46.3 [9.93] 121 47.6 [9.37] Week 44, n Mean [SD] 122 40.8 [12.01] 121 43.4 [11.89] 121 46.0 [10.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.8 [11.87] -2.9 [12.73] -1.6** [8.79] Bodily pain Baseline, n Mean [SD] 122 47.1 [8.04] 121 48.8 [8.17] 121 48.2 [8.67] Week 44, n Mean [SD] 122 42.1 [10.65] 120 45.1 [11.34] 121 46.5 [10.97] Change from baseline Week 44, n 122 120 121 Mean [SD] -5.0 [10.61] -3.8 [11.73] -1.7** [8.87] General health Baseline, n Mean [SD] 122 39.5 [10.37] 121 40.0 [10.54] 121 40.7 [10.06] Week 44, n Mean [SD] 122 37.2 [10.94] 121 39.9 [11.31] 121 40.1 [11.03] Change from baseline Week 44, n 122 121 121 Mean [SD] -2.3 [10.18] -0.1* [10.25] -0.6 [8.78] Vitality Baseline, n Mean [SD]Week 44, n Mean [SD]Change from baseline Week 44, nMean [SD] 122 46.4 [10.27]122 41.4 [12.25]122-5.0 [11.77] 121 47.2 [10.82]120 44.8 [12.83]120-2.4* [12.42] 121 48.6 [10.94]121 45.6 [12.45]121-2.9* [10.38] Social functioning Baseline, n Mean [SD] 122 45.7 [8.89] 121 46.4 [10.17] 121 46.5 [9.54] Week 44, n Mean [SD] 122 41.5 [11.79] 121 44.1 [11.76] 121 45.3 [10.96] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.2 [12.23] -2.3 [13.41] -1.2* [10.06] Role-emotional Baseline, n Mean [SD] 122 45.5 [11.95] 121 46.4 [10.90] 121 47.9 [9.64] Week 44, n Mean [SD] 122 42.2 [13.46] 121 44.6 [12.80] 121 46.5 [11.69] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.3 [11.59] -1.8 [14.04] -1.4 [9.29] Mental health Baseline, n Mean [SD] 122 46.9 [10.68] 121 47.7 [10.11] 121 48.1 [10.30] Week 44, n Mean [SD] 122 42.0 [10.98] 120 45.6 [11.57] 121 47.0 [10.81] Change from baseline Week 44, n 122 120 121 Mean [SD] -4.9 [10.52] -2.3** [11.93] -1.1*** [9.85] IBDQ, Inflammatory Bowel Disease Questionnaire; IV, intravenous; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous; SD, standard deviation; SF-36, 36-Item Short Form Health Survey. aPatients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study. bPatients who had a prohibited Crohn’s disease-related surgery, had a loss of response, had prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be worsened Crohn’s disease before the designated analysis timepoint had their induction baseline value carried forward. cPatients who had insufficient data at the designated analysis timepoint had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large 4. Discussion At study entry, participants in the UNITI trials had active CD with IBDQ and SF-36 scores consistent with moderate to severe impairment of HRQOL.10 Following treatment with IV ustekinumab 6 mg/kg or 130 mg, HRQOL scores improved considerably relative to placebo. At Week 8, greater proportions of patients receiving either ustekinumab 6 mg/kg or 130 mg demonstrated clinically important improvement in total IBDQ scores compared with placebo, with a greater effect evident in those who received the regulatory approved 6 mg/kg dose. Consistent with these observations, greater proportions of patients receiving ustekinumab 6 mg/kg and 130 mg demonstrated clinically significant improvement compared with placebo in both the PCS and MCS scores. Likewise, greater proportions of patients in the ustekinumab 6 mg/kg group achieved normal IBDQ, PCS, and MCS scores. It is noteworthy that HRQOL normalisation was more pronounced among ustekinumab-treated patients with an inadequate response or intolerance to conventional CD therapy [UNITI-2 population] than to TNF antagonists [UNITI-1 population]. This phenomenon, which was also observed in a recent analysis of patients treated with vedolizumab, is likely due to the greater prevalence of structural bowel damage in UNITI-1 participants who had higher disease activity and longer disease duration than those evaluated in UNITI-2. At the baseline visit of IM-UNITI, the mean baseline IBDQ scores approached the criterion for remission [≥170 points] and both PCS and MCS scores approximated the general US population mean norms of 50. At Week 44 in IM-UNITI, a dose-response relationship was observed with patient-reported outcomes, as was previously reported for improvements in signs and symptoms.5 This dose-response relationship favoured patients receiving q8w maintenance dosing compared with q12w dosing. Mean reductions in IBDQ scores from baseline at entry to IM-UNITI [i.e. Week 8] for the ustekinumab q12w and q8w dose groups were both significantly less compared with those assigned to placebo. This was also observed with SF-36 scores, where ustekinumab q8w was more likely to maintain improvement from induction therapy than ustekinumab q12w as measured by both the MCS and the PCS scores. This dose-response between q8w and q12w dosing at Week 44 was more apparent in parameters evaluating the more stringent endpoints of patients achieving clinically-important improvement in IBDQ, PCS, or MCS, or normalisation of IBDQ, PCS, or MCS scores. These results are consistent with the Week 44 primary endpoint [clinical remission] and major secondary endpoints [clinical response, remission in remitters, corticosteroid-free remission, and remission in TNF-naïve patients] where the ustekinumab q8w group was numerically greater than the q12w group for all endpoints.5 Collectively, these findings support the choice of the q8w dose regimen as being optimal for maintaining improved quality of life in patients who responded to induction therapy with ustekinumab. Previous studies with TNF antagonists, including infliximab, natalizumab, adalimumab, and vedolizumab, have shown that maintenance treatment with these therapies results in improved HRQOL in patients as assessed by multiple patient-reported outcome instruments.12–15 In conclusion, ustekinumab improved general health status and inflammatory bowel disease-specific HRQOL after a single intravenous infusion in patients with moderately to severely active CD, particularly ustekinumab 6 mg/kg, and improvements were better maintained with subcutaneous ustekinumab 90 mg q8w or q12w as compared with placebo. These results mirror the efficacy in clinical outcomes and inflammatory biomarkers reported previously.5 Funding This work was supported by Janssen Research & Development, LLC. Conflict of Interest BES has received honoraria for speaking in a CME conference from American Academy of CME, Inc., Catrille & Associates, Ltd, Creative Educational Concepts, Inc., Curatio CME Institute, Focus Medical Communications, LLC, Med-IQ, LLC, Rockpoint, Inc., IMEDEX, Scripps, Strategic Consultants International, and Vindico Medical Education; received consultant fees from Akros Pharma, Arena Pharmaceuticals, Cowen Services Company, LLC, Forest Research Institute, Inc., Forward Pharma, Immune Pharmaceuticals, Inc., MedImmune, Salix Pharmaceuticals, Inc., Strategic Consultants International, Synergy Pharmaceuticals, Theravance Biopharma R&D, Inc., TiGenix, UCB, and Vedanta Biosciences; received consulting fees for services on an advisory board for AbbVie, Amgen, AstraZeneca LP, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Luitpold Pharmaceuticals, Inc., Pfizer, Prometheus Laboratories, Receptos, Takeda, TopiVert Pharma; and received research grants from AbbVie, Amgen, Celgene, Janssen, Pfizer, Prometheus Laboratories, and Takeda. ST reports receiving consulting fees from Janssen Research & Development, LLC. WJS reports grants, personal fees, and non-financial support from AbbVie; grants and personal fees from Prometheus Laboratories, AbbVie, Boehringer Ingelheim, Takeda, Atlantic Pharmaceuticals, Janssen Research & Development, LLC, Bristol-Myers Squibb, Genentech, and Nutrition Science Partners; personal fees from Kyowa Hakko Kirin, Millennium Pharmaceuticals, Celgene Cellular Therapeutics, Santarus, Salix Pharmaceuticals, Catabasis Pharmaceuticals, Vertex Pharmaceuticals, Warner Chilcott, Gilead Sciences, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Sigmoid Biotechnologies, Tillotts Pharma, Am Pharma BV, Dr August Wolff, Avaxia Biologics, Zyngenia, Ironwood Pharmaceuticals, Index Pharmaceuticals, Nestle, Lexicon Pharmaceuticals, UCB Pharma, Orexigen, Luitpold Pharmaceuticals, Baxter Healthcare, Ferring Research Institute, Amgen, Novo Nordisk, Mesoblast, Inc., Shire, Ardelyx Inc., Actavis, Seattle Genetics, MedImmune [AstraZeneca], Actogenix NV, Lipid Therapeutics GmbH, Eisai, Qu Biologics, Toray Industries, Inc., Teva Pharmaceuticals, Eli Lilly, Chiasma, TiGenix, Adherion Therapeutics, Immune Pharmaceuticals, Celgene, Arena Pharmaceuticals, Ambrx, Inc., Akros Pharma, Vascular Biogenics, Theradiag, Forward Pharma, Regeneron, Galapagos, Seres Health, Ritter Pharmaceuticals, Theravance, Palatin, Biogen, and Western University [owner of Robarts Clinical Trials]. BGF has received consulting fees from Abbott/AbbVie, Ablynx, Actogenix, Akebia Therapeutics, Akros, Albireo Pharma, Allergan, Amgen, Applied Molecular Transport, Inc., Astra Zeneca, Atlantic Pharma, Avaxia Biologics, Inc., Avir Pharma, Baxter Healthcare Corp., Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, Galapagos, GiCare Pharma, Gilead, Given Imaging, Inc., GSK, Inception IBD, Inc., Ironwood Pharma, Janssen Research & Development, LLC, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nektar, Nestles, Nextbiotix, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Receptos, Roche/Genentech, Salix Pharma, Serano, Shire, Sigmoid Pharma, Synergy Pharma, Inc., Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, Vivelix Pharma, VHsquared Ltd, Warner-Chilcott, Wyeth, Zealand, Zyngenia; grant/research support from AbbVie, Inc., Amgen, Inc., AstraZeneca/MedImmune Ltd, Atlantic Pharmaceuticals Ltd, Boehringer-Ingelheim, Celgene Corporation, Celltech, Genentech ,Inc.,/Hoffmann-La Roche Ltd, Gilead Sciences, Inc., GlaxoSmithKline [GSK], Janssen Research & Development LLC, Pfizer, Inc., Receptos, Inc./Celgene International, Sanofi, Santarus, Inc., Takeda Development Center Americas, Inc., Tillotts Pharma AG, UCB; served as a Scientific Advisory Board member for Abbott/AbbVie, Allergan, Amgen, Astra Zeneca, Atlantic Pharma, Avaxia Biologics, Inc., Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Inc., Elan/Biogen, Ferring, Galapagos, Genentech/Roche, Janssen Research & Development, LLC, Merck, Nestles, Novartis, Novo Nordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Takeda, Teva, TiGenix, Tillotts Pharma AG, UCB Pharma; has been on the speakers bureau for Abbott/AbbVie, Janssen Research & Development, LLC, Lilly, Takeda, Tillotts, and UCB Pharma; and is a member of the Board of Directors for Robarts Clinical Trials, Inc., Western University, London, ON. CH is an employee of Janssen Biotech, Inc., CG, YL, DJ, L-LG, and PS are employees of Janssen Research & Development, LLC. Author Contributions The study concept and design were developed by BES, ST, WJS, and BGF in collaboration with the sponsor, Janssen Research & Development, LLC, and interpretation of data. BES, ST, WJS, and BGF were involved in the recruitment of study patients. All authors were involved in the analysis and/or interpretation of the data, and were involved in drafting the manuscript and critically reviewing it for important intellectual content. All authors had full access to the data in the study and had final responsibility for the decision to submit for publication. Conference presentations: these data were presented in part at the Annual Meeting of Digestive Diseases Week 2016 [San Diego, CA]. Acknowledgments Editorial and writing support was provided by Kirsten Schuck Gross, BS, and James P Barrett, BS, employees of Janssen Scientific Affairs, LLC. Statistical support was provided by Tianshu Ma, PhD, an employee of PRA Health Sciences funded by Janssen Scientific Affairs, LLC. References 1. Ware JE Jr , Sherbourne CD . The MOS 36-item short-form health survey [SF-36]. I. Conceptual framework and item selection . Med Care 1992 ; 30 : 473 – 83 . Google Scholar CrossRef Search ADS PubMed 2. Irvine EJ , Feagan B , Rochon J et al. Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Canadian Crohn’s Relapse Prevention Trial Study Group . Gastroenterology 1994 ; 106 : 287 – 96 . Google Scholar CrossRef Search ADS PubMed 3. Sands BE , Han C , Gasink C et al. Ustekinumab improves general health status and disease-specific health related quality of life of patients with moderate to severe Crohn’s disease: results from the UNITI and IMUNITI phase 3 clinical trials . Gastroenterology 2016 ; 150 : S1004 [abstract]. Google Scholar CrossRef Search ADS 4. Bernklev T , Jahnsen J , Lygren I , Henriksen M , Vatn M , Moum B . Health-related quality of life in patients with inflammatory bowel disease measured with the short form-36: psychometric assessments and a comparison with general population norms . Inflamm Bowel Dis 2005 ; 11 : 909 – 18 . Google Scholar CrossRef Search ADS PubMed 5. Feagan BG , Sandborn WJ , Gasink C et al. ; UNITI–IM-UNITI Study Group . Ustekinumab as induction and maintenance therapy for Crohn’s disease . N Engl J Med 2016 ; 375 : 1946 – 60 . Google Scholar CrossRef Search ADS PubMed 6. Pallis AG , Vlachonikolis IG , Mouzas IA . Assessing health-related quality of life in patients with inflammatory bowel disease, in Crete, Greece . BMC Gastroenterol 2002 ; 2 : 1 . Google Scholar CrossRef Search ADS PubMed 7. Irvine EJ . Development and subsequent refinement of the inflammatory bowel disease questionnaire: a quality-of-life instrument for adult patients with inflammatory bowel disease . J Pediatr Gastroenterol Nutr 1999 ; 28 : S23 – 7 . Google Scholar CrossRef Search ADS PubMed 8. Kosinski M , Zhao SZ , Dedhiya S , Osterhaus JT , Ware JE Jr . Determining minimally important changes in generic and disease-specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis . Arthritis Rheum 2000 ; 43 : 1478 – 87 . Google Scholar CrossRef Search ADS PubMed 9. Samsa G , Edelman D , Rothman ML , Williams GR , Lipscomb J , Matchar D . Determining clinically important differences in health status measures: a general approach with illustration to the Health Utilities Index Mark II . Pharmacoeconomics 1999 ; 15 : 141 – 55 . Google Scholar CrossRef Search ADS PubMed 10. Hlavaty T , Persoons P , Vermeire S et al. Evaluation of short-term responsiveness and cutoff values of inflammatory bowel disease questionnaire in Crohn’s disease . Inflamm Bowel Dis 2006 ; 12 : 199 – 204 . Google Scholar CrossRef Search ADS PubMed 11. Ware JE , Kosinski M , Keller SD. SF-36 Physical and Mental Health Summary Scales: A User’s Manual . Boston, MA : Health Institute ; 1994 . 12. Feagan BG , Yan S , Bala M , Bao W , Lichtenstein GR . The effects of infliximab maintenance therapy on health-related quality of life . Am J Gastroenterol 2003 ; 98 : 2232 – 8 . Google Scholar CrossRef Search ADS PubMed 13. Feagan BG , Sandborn WJ , Hass S , Niecko T , White J . Health-related quality of life during natalizumab maintenance therapy for Crohn’s disease . Am J Gastroenterol 2007 ; 102 : 2737 – 46 . Google Scholar CrossRef Search ADS PubMed 14. Loftus EV , Feagan BG , Colombel JF et al. Effects of adalimumab maintenance therapy on health-related quality of life of patients with Crohn’s disease: patient-reported outcomes of the CHARM trial . Am J Gastroenterol 2008 ; 103 : 3132 – 41 . Google Scholar CrossRef Search ADS PubMed 15. Feagan BG , Patel H , Colombel JF et al. Effects of vedolizumab on health-related quality of life in patients with ulcerative colitis: results from the randomised GEMINI 1 trial . Aliment Pharmacol Ther 2017 ; 45 : 264 – 75 . Google Scholar CrossRef Search ADS PubMed Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Crohn's and Colitis Oxford University Press

The Effects of Ustekinumab on Health-related Quality of Life in Patients With Moderate to Severe Crohn’s Disease

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Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com
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1873-9946
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1876-4479
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10.1093/ecco-jcc/jjy055
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Abstract

Abstract Background and Aims We assessed the effect of ustekinumab on health-related quality of life [HRQOL] in adults with Crohn’s disease [CD]. Methods Patients with moderately to severely active CD and inadequate response or intolerance to tumour necrosis factor antagonists [UNITI-1, n = 741], or conventional therapy [UNITI-2, n = 627] were randomised to placebo, ustekinumab 130 mg, or 6 mg/kg intravenous induction therapy. At Week 8, ustekinumab-treated responders (Crohn’s Disease Activity Index [CDAI] reduction ≥100 or CDAI <150 points) were re-randomised to subcutaneous maintenance therapy [IM-UNITI, n = 388] with placebo, ustekinumab 90 mg every 12 weeks [q12w], or ustekinumab 90 mg every 8 weeks [q8w], for 44 additional weeks. Inflammatory Bowel Disease Questionnaire [IBDQ] and 36-item Short Form Health Survey [SF-36] physical component summary [PCS] and mental component summary [MCS] scores were completed at induction baseline and Week 8, and at maintenance Weeks 20 and 44. Clinically meaningful improvement in IBDQ and PCS and MCS scores were evaluated. For all HRQOL outcomes, each ustekinumab dose and placebo were compared. Results Induction baseline mean values of IBDQ, PCS, and MCS were similar across groups, but impaired relative to general population norms. At Week 8, ustekinumab induced greater improvement than placebo in both HRQOL scores. Significantly greater proportions of patients receiving ustekinumab 6 mg/kg or 130 mg had clinically meaningful IBDQ improvement [UNITI-1: 54.8%, 46.9% versus 36.5%, respectively; UNITI-2: 68.1%, 58.7% versus 41.1%, respectively; p <0.05, all comparisons]. Similarly, greater proportions of ustekinumab-treated patients in both studies had clinically meaningful improvements in PCS and MCS as compared with placebo. At Week 44, improvements in IBDQ, PCS, and MCS scores were maintained with ustekinumab. Conclusions Ustekinumab improved HRQOL in patients with moderately to severely active CD. Patient-reported outcomes, inflammatory bowel disease questionnaire, medical outcome survey short form-36 1. Introduction Crohn’s disease [CD] often has important negative effects on patients’ health-related quality of life [HRQOL], because of the impacts of disease on both physical and mental well-being. HRQOL is usually assessed by either the 36-item Short-Form Health Survey [SF-36], a generic multi-item scale that evaluates both physical [PCS] and mental component summary scores [MCS],1 or a disease-specific instrument: the Inflammatory Bowel Disease Questionnaire [IBDQ].2 Previous studies have shown that SF-36 is a reliable and valid instrument to measure general health status in patients with CD.3 Importantly, as can only be determined using a generic instrument, patients with CD have substantially impaired HRQOL compared with the general population.4 Furthermore, the effects of the disease on SF-36 MCS scores is relatively more profound than observed in other chronic inflammatory diseases such as rheumatoid arthritis. The IBDQ, a 32-item questionnaire comprising four domains [bowel symptoms, systemic symptoms, emotional function, and social function] is the most commonly used disease-specific measure for evaluation of HRQOL in CD. The IBDQ is more sensitive than the SF-36 to clinically meaningful changes in health status, and therefore can be used to detect relatively small differences in treatment effects in specific disease subgroups or drug treatment regimens. Ustekinumab, a monoclonal antibody to the p40 subunit of interleukins [IL]-12 and -23, is approved for the treatment of active CD based on the results of three Phase 3 studies.5 Herein we report the effects of ustekinumab on HRQOL in patients with moderate to severe CD. 2. Methods The UNITI and IM-UNITI studies were multicentre, randomised, double-blind, placebo-controlled Phase 3 studies designed to evaluate the safety and efficacy of ustekinumab induction and maintenance therapy in patients with moderately to severely active CD. Briefly, patients with moderately to severely active CD (defined by a CD Activity Index [CDAI] score of 220–450) and with inadequate response or intolerance to tumour necrosis factor [TNF] antagonists [UNITI-1] or conventional therapy [UNITI-2], were randomised in a 1:1:1 ratio to receive a single intravenous [IV] infusion of placebo, ustekinumab 130 mg, or weight-range based dosing of approximately 6 mg/kg ustekinumab (260 mg [weight ≤55 kg], 390 mg [weight >55 kg and ≤85 kg], or 520 mg [weight >85 kg], hereafter referred to as 6 mg/kg). Patients with a clinical response [defined as a CDAI reduction ≥100 points or CDAI <150] to ustekinumab at Week 8 were re-randomised into the primary maintenance population in IM-UNITI to receive subcutaneous [SC] placebo, or ustekinumab 90 mg every 12 weeks [q12w], or ustekinumab 90 mg every 8 weeks [q8w], through Week 44 [52 weeks after induction baseline]. 2.1. Assessments Disease-specific HRQOL was measured using the Inflammatory Bowel Disease Questionnaire [IBDQ],2 and generic HRQOL was measured using the SF-361 summary scores [PCS and MCS] and individual item scores, which were completed at Weeks 0 and 8 of the induction studies and at Weeks 20 and 44 of the maintenance study. Clinically meaningful improvements of these measures were defined as an increase of ≥16 points in IBDQ score2,6,7 and ≥5 points in SF-36 PCS and MCS scores.8,9 Patients with an IBDQ score ≥170 points were considered to be in clinical remission.10 Additionally, IBDQ normalisation defined as a score ≥210 points,7 and SF-36 PCS or MCS normalisation defined as scores ≥50 points11 among patients with abnormal baseline values, were also evaluated in post hoc analyses. 2.2. Statistical analysis The Type 1 error rate within each study was controlled at 0.05 for the primary and major secondary endpoints, using a hierarchical testing procedure. The HRQOL outcomes described herein were pre-specified; however, statistical contrasts were not adjusted for multiplicity. thus p-values should be considered nominal. Each ustekinumab group [induction: ustekinumab 130 mg, ustekinumab 6 mg/kg, ustekinumab combined; maintenance: ustekinumab 90 mg q12w, ustekinumab 90 mg q8w] was compared with the placebo group. Continuous outcomes [mean change from baseline in SF-36 component summary and scale scores at Week 8, Week 20, and Week 44; mean change from baseline in IBDQ total and domain scores at Week 8, Week 20, and Week 44] were analysed by analysis of covariance on van der Waerden normal scores. Proportions of patients with dichotomous outcomes [clinically meaningful improvements or normalised values] in IBDQ, PCS, and MCS at Week 8 and Week 44 were compared using a Cochran-Mantel-Haenszel chi-square test. The following missing data conventions were used for these analyses. Each of the four individual IBDQ dimensions was calculated when ≤1 item was missing in the dimension. The missing item was estimated using the average value across the non-missing items. If any one of the dimensions within the IBDQ could not be calculated, then the total IBDQ score was not be calculated. For SF-36 scores, subscales were calculated whenever ≥50% of the items that comprised the individual subscale were available [non-missing]. Any missing items were estimated using the average value across the non-missing items for that subscale. If <50% of the items that comprised the subscale were available, the subscale was not calculated. If any of the individual subscales that comprised the PCS or MCS score was missing, then these scores could not be calculated. 3. Results 3.1. Induction studies Baseline disease characteristics in both the UNITI-1 and UNITI-2 study populations were representative of patients with moderately to severely active CD refractory to either TNF antagonists [UNITI-1] or conventional therapies [UNITI-2]. Median disease duration was 6.4 and 10.1 years and median CDAI scores were 292.5 and 317.0 in UNITI-2 and 1, respectively. Median C-reactive protein [CRP] concentrations were 8.05 mg/L in UNITI-2 and 9.88 mg/L in UNITI-1. Higher values for CDAI score and CRP concentrations are consistent with higher disease activity in the TNF-antagonist failure UNITI-1 population. 3.1.1. IBDQ results In both UNITI-1 and UNITI-2, mean (standard deviation[SD]) baseline IBDQ scores for placebo, ustekinumab 130 mg, and ustekinumab 6 mg/kg (UNITI-1: 120.0 [29.27], 119.5 [29.47], and 118.2 [26.64], respectively; UNITI-2: 122.7 [31.32], 118.2 [30.99], and 122.8 [31.62], respectively) were similar across treatment groups, consistent with substantially impaired HRQOL. Following initiation of induction therapy, significantly greater improvement was observed for both ustekinumab doses in comparison with placebo [Table 1; Figure 1A, B]. A numerically greater treatment effect relative to placebo was seen in UNITI-2 than UNITI-1 [ustekinumab 130 mg, 14.4 versus 6.2; ustekinumab 6 mg/kg, 20.6 versus 10.2, respectively]. Table 1. Mean [SD] and mean change [SD] from baseline in the IBDQ and SF-36 scores at Week 8 of induction therapy. UNITI-1 UNITI-2 Ustekinumab Ustekinumab Patient- reportedOutcome Placebo 130 mg 6 mg/kga Combined Placebo 130 mg 6 mg/kga Combined IBDQ score, n = 247 245 249 494 209 209 209 418 Baseline, n 244 243 248 491 207 208 207 415 Mean [SD] 120.0 [29.27] 119.5 [29.47] 118.2 [26.64] 118.8 [28.06] 122.7 [31.32] 118.2 [30.99] 122.8 [31.62] 120.5 [31.35] Week 8, n 244 243 248 491 207 208 207 415 Mean [SD] 131.9 [34.61] 137.5 [37.95] 140.3 [34.39] 138.9 [36.19] 137.3 [37.33] 147.3 [36.74] 158.0 [34.54] 152.6 [36.02] Change from baseline Week 8b,c, n 244 243 248 491 207 208 207 415 Mean [SD] 11.9 [26.51] 18.1* [28.02] 22.1*** [28.59] 20.1*** [28.35] 14.7 [26.96] 29.1*** [33.82] 35.3*** [36.05] 32.2*** [35.04] SF-36 score, n 225 231 235 466 190 194 196 390 Physical component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [7.12] 37.8 [7.12] 37.2 [7.09] 37.5 [7.11] 39.7 [7.19] 38.9 [7.62] 38.9 [7.05] 38.9 [7.33]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.4 [7.56] 41.0 [8.32] 40.7 [8.48] 40.9 [8.39] 42.3 [7.79] 44.0 [8.39] 44.9 [8.75] 44.4 [8.57]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.6 [6.50] 3.2 [6.43] 3.6 [6.75] 3.4 [6.60] 2.6 [5.88] 5.1** [7.24] 6.0*** [7.70] 5.5*** [7.48] Mental component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [10.64] 37.3 [9.98] 36.4 [9.89] 36.9 [9.93] 37.1 [10.75] 37.2 [10.81] 37.9 [11.15] 37.6 [10.98]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.0 [11.38] 40.6 [11.79] 41.3 [10.45] 41.0 [11.13] 40.4 [11.79] 43.1 [11.36] 44.7 [10.72] 43.9 [11.06]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.2 [8.47] 3.3 [9.41] 4.9** [9.28] 4.1* [9.37] 3.3 [9.47] 5.9** [10.55] 6.8*** [11.34] 6.4*** [10.95] UNITI-1 UNITI-2 Ustekinumab Ustekinumab Patient- reportedOutcome Placebo 130 mg 6 mg/kga Combined Placebo 130 mg 6 mg/kga Combined IBDQ score, n = 247 245 249 494 209 209 209 418 Baseline, n 244 243 248 491 207 208 207 415 Mean [SD] 120.0 [29.27] 119.5 [29.47] 118.2 [26.64] 118.8 [28.06] 122.7 [31.32] 118.2 [30.99] 122.8 [31.62] 120.5 [31.35] Week 8, n 244 243 248 491 207 208 207 415 Mean [SD] 131.9 [34.61] 137.5 [37.95] 140.3 [34.39] 138.9 [36.19] 137.3 [37.33] 147.3 [36.74] 158.0 [34.54] 152.6 [36.02] Change from baseline Week 8b,c, n 244 243 248 491 207 208 207 415 Mean [SD] 11.9 [26.51] 18.1* [28.02] 22.1*** [28.59] 20.1*** [28.35] 14.7 [26.96] 29.1*** [33.82] 35.3*** [36.05] 32.2*** [35.04] SF-36 score, n 225 231 235 466 190 194 196 390 Physical component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [7.12] 37.8 [7.12] 37.2 [7.09] 37.5 [7.11] 39.7 [7.19] 38.9 [7.62] 38.9 [7.05] 38.9 [7.33]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.4 [7.56] 41.0 [8.32] 40.7 [8.48] 40.9 [8.39] 42.3 [7.79] 44.0 [8.39] 44.9 [8.75] 44.4 [8.57]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.6 [6.50] 3.2 [6.43] 3.6 [6.75] 3.4 [6.60] 2.6 [5.88] 5.1** [7.24] 6.0*** [7.70] 5.5*** [7.48] Mental component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [10.64] 37.3 [9.98] 36.4 [9.89] 36.9 [9.93] 37.1 [10.75] 37.2 [10.81] 37.9 [11.15] 37.6 [10.98]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.0 [11.38] 40.6 [11.79] 41.3 [10.45] 41.0 [11.13] 40.4 [11.79] 43.1 [11.36] 44.7 [10.72] 43.9 [11.06]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.2 [8.47] 3.3 [9.41] 4.9** [9.28] 4.1* [9.37] 3.3 [9.47] 5.9** [10.55] 6.8*** [11.34] 6.4*** [10.95] IBDQ, Inflammatory Bowel Disease Questionnaire; SD, standard deviation; SF-36, 36-Item Short Form Health Survey. aWeight-range based ustekinumab doses approximating 6 mg/kg: 260 mg [weight ≤55 kg], 390 mg [weight >55 kg and ≤85 kg], 520 mg [weight >85 kg]. bPatients who had a prohibited Crohn’s disease-related surgery or had prohibited concomitant medication changes before Week 8 had their baseline value carried forward. cPatients who had insufficient data at Week 8 had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Table 1. Mean [SD] and mean change [SD] from baseline in the IBDQ and SF-36 scores at Week 8 of induction therapy. UNITI-1 UNITI-2 Ustekinumab Ustekinumab Patient- reportedOutcome Placebo 130 mg 6 mg/kga Combined Placebo 130 mg 6 mg/kga Combined IBDQ score, n = 247 245 249 494 209 209 209 418 Baseline, n 244 243 248 491 207 208 207 415 Mean [SD] 120.0 [29.27] 119.5 [29.47] 118.2 [26.64] 118.8 [28.06] 122.7 [31.32] 118.2 [30.99] 122.8 [31.62] 120.5 [31.35] Week 8, n 244 243 248 491 207 208 207 415 Mean [SD] 131.9 [34.61] 137.5 [37.95] 140.3 [34.39] 138.9 [36.19] 137.3 [37.33] 147.3 [36.74] 158.0 [34.54] 152.6 [36.02] Change from baseline Week 8b,c, n 244 243 248 491 207 208 207 415 Mean [SD] 11.9 [26.51] 18.1* [28.02] 22.1*** [28.59] 20.1*** [28.35] 14.7 [26.96] 29.1*** [33.82] 35.3*** [36.05] 32.2*** [35.04] SF-36 score, n 225 231 235 466 190 194 196 390 Physical component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [7.12] 37.8 [7.12] 37.2 [7.09] 37.5 [7.11] 39.7 [7.19] 38.9 [7.62] 38.9 [7.05] 38.9 [7.33]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.4 [7.56] 41.0 [8.32] 40.7 [8.48] 40.9 [8.39] 42.3 [7.79] 44.0 [8.39] 44.9 [8.75] 44.4 [8.57]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.6 [6.50] 3.2 [6.43] 3.6 [6.75] 3.4 [6.60] 2.6 [5.88] 5.1** [7.24] 6.0*** [7.70] 5.5*** [7.48] Mental component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [10.64] 37.3 [9.98] 36.4 [9.89] 36.9 [9.93] 37.1 [10.75] 37.2 [10.81] 37.9 [11.15] 37.6 [10.98]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.0 [11.38] 40.6 [11.79] 41.3 [10.45] 41.0 [11.13] 40.4 [11.79] 43.1 [11.36] 44.7 [10.72] 43.9 [11.06]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.2 [8.47] 3.3 [9.41] 4.9** [9.28] 4.1* [9.37] 3.3 [9.47] 5.9** [10.55] 6.8*** [11.34] 6.4*** [10.95] UNITI-1 UNITI-2 Ustekinumab Ustekinumab Patient- reportedOutcome Placebo 130 mg 6 mg/kga Combined Placebo 130 mg 6 mg/kga Combined IBDQ score, n = 247 245 249 494 209 209 209 418 Baseline, n 244 243 248 491 207 208 207 415 Mean [SD] 120.0 [29.27] 119.5 [29.47] 118.2 [26.64] 118.8 [28.06] 122.7 [31.32] 118.2 [30.99] 122.8 [31.62] 120.5 [31.35] Week 8, n 244 243 248 491 207 208 207 415 Mean [SD] 131.9 [34.61] 137.5 [37.95] 140.3 [34.39] 138.9 [36.19] 137.3 [37.33] 147.3 [36.74] 158.0 [34.54] 152.6 [36.02] Change from baseline Week 8b,c, n 244 243 248 491 207 208 207 415 Mean [SD] 11.9 [26.51] 18.1* [28.02] 22.1*** [28.59] 20.1*** [28.35] 14.7 [26.96] 29.1*** [33.82] 35.3*** [36.05] 32.2*** [35.04] SF-36 score, n 225 231 235 466 190 194 196 390 Physical component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [7.12] 37.8 [7.12] 37.2 [7.09] 37.5 [7.11] 39.7 [7.19] 38.9 [7.62] 38.9 [7.05] 38.9 [7.33]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.4 [7.56] 41.0 [8.32] 40.7 [8.48] 40.9 [8.39] 42.3 [7.79] 44.0 [8.39] 44.9 [8.75] 44.4 [8.57]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.6 [6.50] 3.2 [6.43] 3.6 [6.75] 3.4 [6.60] 2.6 [5.88] 5.1** [7.24] 6.0*** [7.70] 5.5*** [7.48] Mental component summary  Baseline, n 223 231 232 463 189 193 195 388  Mean [SD] 37.8 [10.64] 37.3 [9.98] 36.4 [9.89] 36.9 [9.93] 37.1 [10.75] 37.2 [10.81] 37.9 [11.15] 37.6 [10.98]  Week 8, n 223 231 232 463 189 193 195 388  Mean [SD] 40.0 [11.38] 40.6 [11.79] 41.3 [10.45] 41.0 [11.13] 40.4 [11.79] 43.1 [11.36] 44.7 [10.72] 43.9 [11.06]  Change from baseline  Week 8b,c, n 223 231 232 463 189 193 195 388  Mean [SD] 2.2 [8.47] 3.3 [9.41] 4.9** [9.28] 4.1* [9.37] 3.3 [9.47] 5.9** [10.55] 6.8*** [11.34] 6.4*** [10.95] IBDQ, Inflammatory Bowel Disease Questionnaire; SD, standard deviation; SF-36, 36-Item Short Form Health Survey. aWeight-range based ustekinumab doses approximating 6 mg/kg: 260 mg [weight ≤55 kg], 390 mg [weight >55 kg and ≤85 kg], 520 mg [weight >85 kg]. bPatients who had a prohibited Crohn’s disease-related surgery or had prohibited concomitant medication changes before Week 8 had their baseline value carried forward. cPatients who had insufficient data at Week 8 had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Figure 1. View largeDownload slide Mean baseline and Week 8, and mean change in IBDQ, PCS, and MCS scores with induction therapy [UNITI-1: A, C, E; UNITI-2: B, D, F]. Figure 1. View largeDownload slide Mean baseline and Week 8, and mean change in IBDQ, PCS, and MCS scores with induction therapy [UNITI-1: A, C, E; UNITI-2: B, D, F]. For both studies, changes in the mean IBDQ scores at Week 8 were significantly greater in both ustekinumab dose groups compared with placebo and across all dimensions [p <0.05 for all comparisons]. In both studies, changes in the mean IBDQ dimension scores at Week 8 were significantly greater in the ustekinumab 6 mg/kg group compared with placebo and across all dimensions [p <0.001 for all comparisons]. In the ustekinumab 130 mg group, mean changes at Week 8 were significantly greater for the social and systemic dimensions [p <0.05 for both comparisons], and numerically greater for the bowel and emotional dimensions compared with placebo in UNITI-1 [Table 2]. Mean changes at Week 8 were significantly greater across all four dimensions when compared with placebo [p <0.001 for both comparisons] in UNITI-2 [Table 2]. Table 2. Mean [SD] and mean change [SD] from baseline in IBDQ domain and SF-36 scale scores at Week 8 of induction therapy. UNITI-1 UNITI-2 Patient-reportedoutcome Ustekinumab Ustekinumab Placebo 130 mg 6 mga Placebo 130 mg 6 mga IBDQ score, nb,c 247 245 249 209 209 209 Bowel symptoms  Baseline, n  Mean [SD] 245 38.6 [9.28] 244 38.2 [8.81] 248 38.5 [8.27] 207 38.8 [9.14] 209 38.2 [9.21] 208 38.9 [9.19]  Week 8, n  Mean [SD] 245 42.6 [10.31] 244 43.7 [11.27] 248 45.1 [10.01] 207 43.9 [11.02] 209 47.5[10.96] 208 50.6 [10.88]  Change at Week 8, n  Mean [SD] 245 4.0 [8.81] 244 5.5 [9.04] 248 6.6*** [8.56] 207 5.1 [8.78] 209 9.3*** [10.76] 208 11.7*** [11.21] Emotional functions  Baseline, n  Mean [SD] 245 46.5 [13.32] 243 47.0 [13.75] 248 45.9 [11.93] 207 46.7 [14.17] 209 44.3 [13.56] 208 46.8 [14.44]  Week 8, n  Mean [SD] 245 50.7 [14.99] 243 52.8 [16.06] 248 53.7 [14.20] 207 51.2 [15.71] 209 54.5 [15.28] 208 58.6 [14.43]  Change at Week 8, n  Mean [SD] 245 4.2 [10.52] 243 5.8 [11.53] 248 7.7*** [11.82] 207 4.5 [10.79] 209 10.1*** [13.95] 208 11.9*** [14.88] Systemic symptoms Baseline, n Mean [SD] 245 15.2 [5.25] 245 14.9 [4.74] 248 14.6 [4.97] 209 15.7 [5.35] 209 15.2 [5.11] 208 15.8 [5.23] Week 8, n Mean [SD] 245 17.3 [6.09] 245 18.3 [6.52] 248 18.5 [6.60] 209 18.5 [6.46] 209 20.0 [6.61] 208 21.8 [5.94] Change at Week 8, n Mean [SD] 245 2.1 [5.10] 245 3.4* [5.65] 248 3.9*** [5.57] 209 2.8 [5.17] 209 4.8*** [6.09] 208 6.0*** [6.29] Social functions Baseline Mean [SD] 244 19.8 [7.35] 244 19.3 [7.44] 248 19.2 [7.15] 209 21.5 [7.21] 208 20.4 [7.44] 209 21.4 [7.37] Week 8 n Mean [SD] 244 21.3 [8.09] 244 22.6 [8.23] 248 23.0 [7.99] 209 23.8 [7.75] 208 25.2 [7.65] 209 26.9 [6.97] Change at Week 8, n, Mean [SD] 244 1.5 [6.03] 244 3.3** [6.14] 248 3.8*** [6.63] 209 2.3 [5.67] 208 4.8*** [6.69] 209 5.6*** [7.12] SF-36 Score, n=b,c 225 231 235 190 194 196 Physical functioning Baseline, n Mean [SD] 224 44.2 [8.52] 231 44.3 [8.61] 234 43.5 [8.70] 190 44.9 [9.57] 193 44.2 [9.38] 196 43.7 [9.13] Week 8, n Mean [SD] 224 45.9 [8.67] 231 46.7 [9.23] 234 45.9 [9.52] 190 46.6 [9.21] 193 47.9 [8.45] 196 47.9 [8.65] Change at Week 8, n Mean [SD] 224 1.7 [6.58] 231 2.4 [6.76] 234 2.4 [7.27] 190 1.8 [6.68] 193 3.7* [7.36] 196 4.2** [7.09] Role-physical Baseline, n Mean [SD] 223 35.2 [8.87] 231 35.5 [9.51] 234 34.7 [9.45] 190 37.7 [9.36] 193 37.2 [9.92] 195 37.1 [9.64] Week 8, n Mean [SD] 223 39.1 [10.09] 231 39.6 [10.95] 234 39.7 [11.17] 190 40.8 [10.30] 193 43.3 [10.36] 195 44.3 [10.07] Change at Week 8, n Mean [SD] 223 3.9 [8.70] 231 4.1 [8.95] 234 5.0 [9.51] 190 3.1 [7.67] 193 6.1*** [8.60] 195 7.2*** [9.87] Bodily pain Baseline, n Mean [SD] 224 37.8 [8.11] 231 36.3 [7.03] 233 36.3 [7.72] 190 36.8 [7.27] 193 36.6 [8.20] 195 37.3 [7.27] Week 8, n Mean [SD] 224 40.3 [9.09] 231 40.5 [8.87] 233 41.7 [9.20] 190 40.6 [8.91] 193 43.3 [9.61] 195 45.8 [9.04] Change at Week 8, n Mean [SD] 224 2.5 [7.75] 231 4.1 [8.02] 233 5.4*** [8.07] 190 3.8 [7.31] 193 6.8** [9.47] 195 8.5*** [10.00] General health Baseline, n Mean [SD] 224 31.7 [7.59] 231 31.7 [6.70] 234 30.4 [6.89] 190 33.6 [8.69] 193 32.9 [8.45] 196 33.4 [7.47] Week 8, n Mean [SD] 224 33.2 [8.46] 231 34.0 [8.56] 234 33.4 [8.18] 190 36.3 [9.17] 193 37.8 [10.50] 196 38.9 [10.40] Change at Week 8, n Mean [SD] 224 1.6 [6.30] 231 2.4 [6.51] 234 2.9 [6.54] 190 2.7 [7.20] 193 4.8* [8.79] 196 5.6*** [9.36] Vitality Baseline, n Mean [SD] 224 35.5 [9.21] 231 35.3 [8.28] 232 34.8 [8.29] 189 36.9 [9.15] 193 36.3 [9.13] 196 37.7 [9.57] Week 8, n Mean [SD] 224 38.8 [10.05] 231 39.7 [10.49] 232 39.8 [10.19] 189 40.7 [10.95] 193 43.4 [11.82] 196 45.2 [10.91] Change at Week 8, n Mean [SD] 224 3.3 [8.12] 231 4.5 [9.43] 232 5.0* [9.05] 189 3.8 [9.17] 193 7.2** [10.46] 196 7.6*** [10.32] Social functioning Baseline, n Mean [SD] 224 35.2 [10.04] 231 35.6 [9.57] 234 34.1 [9.41] 190 36.8 [10.50] 193 36.6 [10.18] 195 36.2 [9.95] Week 8, n Mean [SD] 224 38.2 [10.97] 231 39.0 [11.03] 234 40.0 [10.63] 190 40.2 [11.36] 193 43.2 [10.79] 195 44.1 [9.86] Change at Week 8, n Mean [SD] 224 3.0 [9.24] 231 3.5 [9.76] 234 5.9** [9.50] 190 3.4 [9.55] 193 6.6** [11.04] 195 7.9*** [11.11] Role-emotional Baseline, n Mean [SD] 223 38.9 [12.51] 231 38.5 [12.17] 234 37.7 [12.48] 190 38.5 [12.39] 193 38.4 [12.86] 195 38.7 [11.97] Week 8, n Mean [SD] 223 40.7 [12.53] 231 41.9 [13.09] 234 41.5 [12.74] 190 41.3 [12.34] 193 43.7 [11.85] 195 44.8 [10.78] Change at Week 8, n Mean [SD] 223 1.9 [10.72] 231 3.4 [10.84] 234 3.8 [11.30] 190 2.8 [10.80] 193 5.3* [10.47] 195 6.1** [12.34] Mental health Baseline, n Mean [SD] 224 40.5 [10.63] 231 39.5 [10.26] 232 38.8 [9.34] 189 38.6 [11.16] 193 38.8 [10.51] 196 39.6 [11.37] Week 8, n Mean [SD] 224 42.4 [11.35] 231 42.3 [11.49] 232 43.3 [10.24] 189 41.6 [11.94] 193 44.0 [11.32] 196 45.7 [11.00] Change at Week 8, n Mean [SD] 224 1.9 [8.17] 231 2.8 [9.34] 232 4.5** [8.59] 189 3.0 [8.56] 193 5.2* [10.29] 196 6.1*** [10.91] UNITI-1 UNITI-2 Patient-reportedoutcome Ustekinumab Ustekinumab Placebo 130 mg 6 mga Placebo 130 mg 6 mga IBDQ score, nb,c 247 245 249 209 209 209 Bowel symptoms  Baseline, n  Mean [SD] 245 38.6 [9.28] 244 38.2 [8.81] 248 38.5 [8.27] 207 38.8 [9.14] 209 38.2 [9.21] 208 38.9 [9.19]  Week 8, n  Mean [SD] 245 42.6 [10.31] 244 43.7 [11.27] 248 45.1 [10.01] 207 43.9 [11.02] 209 47.5[10.96] 208 50.6 [10.88]  Change at Week 8, n  Mean [SD] 245 4.0 [8.81] 244 5.5 [9.04] 248 6.6*** [8.56] 207 5.1 [8.78] 209 9.3*** [10.76] 208 11.7*** [11.21] Emotional functions  Baseline, n  Mean [SD] 245 46.5 [13.32] 243 47.0 [13.75] 248 45.9 [11.93] 207 46.7 [14.17] 209 44.3 [13.56] 208 46.8 [14.44]  Week 8, n  Mean [SD] 245 50.7 [14.99] 243 52.8 [16.06] 248 53.7 [14.20] 207 51.2 [15.71] 209 54.5 [15.28] 208 58.6 [14.43]  Change at Week 8, n  Mean [SD] 245 4.2 [10.52] 243 5.8 [11.53] 248 7.7*** [11.82] 207 4.5 [10.79] 209 10.1*** [13.95] 208 11.9*** [14.88] Systemic symptoms Baseline, n Mean [SD] 245 15.2 [5.25] 245 14.9 [4.74] 248 14.6 [4.97] 209 15.7 [5.35] 209 15.2 [5.11] 208 15.8 [5.23] Week 8, n Mean [SD] 245 17.3 [6.09] 245 18.3 [6.52] 248 18.5 [6.60] 209 18.5 [6.46] 209 20.0 [6.61] 208 21.8 [5.94] Change at Week 8, n Mean [SD] 245 2.1 [5.10] 245 3.4* [5.65] 248 3.9*** [5.57] 209 2.8 [5.17] 209 4.8*** [6.09] 208 6.0*** [6.29] Social functions Baseline Mean [SD] 244 19.8 [7.35] 244 19.3 [7.44] 248 19.2 [7.15] 209 21.5 [7.21] 208 20.4 [7.44] 209 21.4 [7.37] Week 8 n Mean [SD] 244 21.3 [8.09] 244 22.6 [8.23] 248 23.0 [7.99] 209 23.8 [7.75] 208 25.2 [7.65] 209 26.9 [6.97] Change at Week 8, n, Mean [SD] 244 1.5 [6.03] 244 3.3** [6.14] 248 3.8*** [6.63] 209 2.3 [5.67] 208 4.8*** [6.69] 209 5.6*** [7.12] SF-36 Score, n=b,c 225 231 235 190 194 196 Physical functioning Baseline, n Mean [SD] 224 44.2 [8.52] 231 44.3 [8.61] 234 43.5 [8.70] 190 44.9 [9.57] 193 44.2 [9.38] 196 43.7 [9.13] Week 8, n Mean [SD] 224 45.9 [8.67] 231 46.7 [9.23] 234 45.9 [9.52] 190 46.6 [9.21] 193 47.9 [8.45] 196 47.9 [8.65] Change at Week 8, n Mean [SD] 224 1.7 [6.58] 231 2.4 [6.76] 234 2.4 [7.27] 190 1.8 [6.68] 193 3.7* [7.36] 196 4.2** [7.09] Role-physical Baseline, n Mean [SD] 223 35.2 [8.87] 231 35.5 [9.51] 234 34.7 [9.45] 190 37.7 [9.36] 193 37.2 [9.92] 195 37.1 [9.64] Week 8, n Mean [SD] 223 39.1 [10.09] 231 39.6 [10.95] 234 39.7 [11.17] 190 40.8 [10.30] 193 43.3 [10.36] 195 44.3 [10.07] Change at Week 8, n Mean [SD] 223 3.9 [8.70] 231 4.1 [8.95] 234 5.0 [9.51] 190 3.1 [7.67] 193 6.1*** [8.60] 195 7.2*** [9.87] Bodily pain Baseline, n Mean [SD] 224 37.8 [8.11] 231 36.3 [7.03] 233 36.3 [7.72] 190 36.8 [7.27] 193 36.6 [8.20] 195 37.3 [7.27] Week 8, n Mean [SD] 224 40.3 [9.09] 231 40.5 [8.87] 233 41.7 [9.20] 190 40.6 [8.91] 193 43.3 [9.61] 195 45.8 [9.04] Change at Week 8, n Mean [SD] 224 2.5 [7.75] 231 4.1 [8.02] 233 5.4*** [8.07] 190 3.8 [7.31] 193 6.8** [9.47] 195 8.5*** [10.00] General health Baseline, n Mean [SD] 224 31.7 [7.59] 231 31.7 [6.70] 234 30.4 [6.89] 190 33.6 [8.69] 193 32.9 [8.45] 196 33.4 [7.47] Week 8, n Mean [SD] 224 33.2 [8.46] 231 34.0 [8.56] 234 33.4 [8.18] 190 36.3 [9.17] 193 37.8 [10.50] 196 38.9 [10.40] Change at Week 8, n Mean [SD] 224 1.6 [6.30] 231 2.4 [6.51] 234 2.9 [6.54] 190 2.7 [7.20] 193 4.8* [8.79] 196 5.6*** [9.36] Vitality Baseline, n Mean [SD] 224 35.5 [9.21] 231 35.3 [8.28] 232 34.8 [8.29] 189 36.9 [9.15] 193 36.3 [9.13] 196 37.7 [9.57] Week 8, n Mean [SD] 224 38.8 [10.05] 231 39.7 [10.49] 232 39.8 [10.19] 189 40.7 [10.95] 193 43.4 [11.82] 196 45.2 [10.91] Change at Week 8, n Mean [SD] 224 3.3 [8.12] 231 4.5 [9.43] 232 5.0* [9.05] 189 3.8 [9.17] 193 7.2** [10.46] 196 7.6*** [10.32] Social functioning Baseline, n Mean [SD] 224 35.2 [10.04] 231 35.6 [9.57] 234 34.1 [9.41] 190 36.8 [10.50] 193 36.6 [10.18] 195 36.2 [9.95] Week 8, n Mean [SD] 224 38.2 [10.97] 231 39.0 [11.03] 234 40.0 [10.63] 190 40.2 [11.36] 193 43.2 [10.79] 195 44.1 [9.86] Change at Week 8, n Mean [SD] 224 3.0 [9.24] 231 3.5 [9.76] 234 5.9** [9.50] 190 3.4 [9.55] 193 6.6** [11.04] 195 7.9*** [11.11] Role-emotional Baseline, n Mean [SD] 223 38.9 [12.51] 231 38.5 [12.17] 234 37.7 [12.48] 190 38.5 [12.39] 193 38.4 [12.86] 195 38.7 [11.97] Week 8, n Mean [SD] 223 40.7 [12.53] 231 41.9 [13.09] 234 41.5 [12.74] 190 41.3 [12.34] 193 43.7 [11.85] 195 44.8 [10.78] Change at Week 8, n Mean [SD] 223 1.9 [10.72] 231 3.4 [10.84] 234 3.8 [11.30] 190 2.8 [10.80] 193 5.3* [10.47] 195 6.1** [12.34] Mental health Baseline, n Mean [SD] 224 40.5 [10.63] 231 39.5 [10.26] 232 38.8 [9.34] 189 38.6 [11.16] 193 38.8 [10.51] 196 39.6 [11.37] Week 8, n Mean [SD] 224 42.4 [11.35] 231 42.3 [11.49] 232 43.3 [10.24] 189 41.6 [11.94] 193 44.0 [11.32] 196 45.7 [11.00] Change at Week 8, n Mean [SD] 224 1.9 [8.17] 231 2.8 [9.34] 232 4.5** [8.59] 189 3.0 [8.56] 193 5.2* [10.29] 196 6.1*** [10.91] IBDQ, Inflammatory Bowel Disease Questionnaire; SD, standard deviation; SF-36, 36-Item Short Form Health Survey. aWeight-range based ustekinumab doses approximating 6 mg/kg: 260 mg [weight ≤55 kg], 390 mg [weight >55 kg and ≤85 kg], 520 mg [weight >85 kg]. bPatients who had a prohibited Crohn’s disease-related surgery or had prohibited concomitant medication changes before Week 8 had their baseline value carried forward. cPatients who had insufficient data at Week 8 had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Table 2. Mean [SD] and mean change [SD] from baseline in IBDQ domain and SF-36 scale scores at Week 8 of induction therapy. UNITI-1 UNITI-2 Patient-reportedoutcome Ustekinumab Ustekinumab Placebo 130 mg 6 mga Placebo 130 mg 6 mga IBDQ score, nb,c 247 245 249 209 209 209 Bowel symptoms  Baseline, n  Mean [SD] 245 38.6 [9.28] 244 38.2 [8.81] 248 38.5 [8.27] 207 38.8 [9.14] 209 38.2 [9.21] 208 38.9 [9.19]  Week 8, n  Mean [SD] 245 42.6 [10.31] 244 43.7 [11.27] 248 45.1 [10.01] 207 43.9 [11.02] 209 47.5[10.96] 208 50.6 [10.88]  Change at Week 8, n  Mean [SD] 245 4.0 [8.81] 244 5.5 [9.04] 248 6.6*** [8.56] 207 5.1 [8.78] 209 9.3*** [10.76] 208 11.7*** [11.21] Emotional functions  Baseline, n  Mean [SD] 245 46.5 [13.32] 243 47.0 [13.75] 248 45.9 [11.93] 207 46.7 [14.17] 209 44.3 [13.56] 208 46.8 [14.44]  Week 8, n  Mean [SD] 245 50.7 [14.99] 243 52.8 [16.06] 248 53.7 [14.20] 207 51.2 [15.71] 209 54.5 [15.28] 208 58.6 [14.43]  Change at Week 8, n  Mean [SD] 245 4.2 [10.52] 243 5.8 [11.53] 248 7.7*** [11.82] 207 4.5 [10.79] 209 10.1*** [13.95] 208 11.9*** [14.88] Systemic symptoms Baseline, n Mean [SD] 245 15.2 [5.25] 245 14.9 [4.74] 248 14.6 [4.97] 209 15.7 [5.35] 209 15.2 [5.11] 208 15.8 [5.23] Week 8, n Mean [SD] 245 17.3 [6.09] 245 18.3 [6.52] 248 18.5 [6.60] 209 18.5 [6.46] 209 20.0 [6.61] 208 21.8 [5.94] Change at Week 8, n Mean [SD] 245 2.1 [5.10] 245 3.4* [5.65] 248 3.9*** [5.57] 209 2.8 [5.17] 209 4.8*** [6.09] 208 6.0*** [6.29] Social functions Baseline Mean [SD] 244 19.8 [7.35] 244 19.3 [7.44] 248 19.2 [7.15] 209 21.5 [7.21] 208 20.4 [7.44] 209 21.4 [7.37] Week 8 n Mean [SD] 244 21.3 [8.09] 244 22.6 [8.23] 248 23.0 [7.99] 209 23.8 [7.75] 208 25.2 [7.65] 209 26.9 [6.97] Change at Week 8, n, Mean [SD] 244 1.5 [6.03] 244 3.3** [6.14] 248 3.8*** [6.63] 209 2.3 [5.67] 208 4.8*** [6.69] 209 5.6*** [7.12] SF-36 Score, n=b,c 225 231 235 190 194 196 Physical functioning Baseline, n Mean [SD] 224 44.2 [8.52] 231 44.3 [8.61] 234 43.5 [8.70] 190 44.9 [9.57] 193 44.2 [9.38] 196 43.7 [9.13] Week 8, n Mean [SD] 224 45.9 [8.67] 231 46.7 [9.23] 234 45.9 [9.52] 190 46.6 [9.21] 193 47.9 [8.45] 196 47.9 [8.65] Change at Week 8, n Mean [SD] 224 1.7 [6.58] 231 2.4 [6.76] 234 2.4 [7.27] 190 1.8 [6.68] 193 3.7* [7.36] 196 4.2** [7.09] Role-physical Baseline, n Mean [SD] 223 35.2 [8.87] 231 35.5 [9.51] 234 34.7 [9.45] 190 37.7 [9.36] 193 37.2 [9.92] 195 37.1 [9.64] Week 8, n Mean [SD] 223 39.1 [10.09] 231 39.6 [10.95] 234 39.7 [11.17] 190 40.8 [10.30] 193 43.3 [10.36] 195 44.3 [10.07] Change at Week 8, n Mean [SD] 223 3.9 [8.70] 231 4.1 [8.95] 234 5.0 [9.51] 190 3.1 [7.67] 193 6.1*** [8.60] 195 7.2*** [9.87] Bodily pain Baseline, n Mean [SD] 224 37.8 [8.11] 231 36.3 [7.03] 233 36.3 [7.72] 190 36.8 [7.27] 193 36.6 [8.20] 195 37.3 [7.27] Week 8, n Mean [SD] 224 40.3 [9.09] 231 40.5 [8.87] 233 41.7 [9.20] 190 40.6 [8.91] 193 43.3 [9.61] 195 45.8 [9.04] Change at Week 8, n Mean [SD] 224 2.5 [7.75] 231 4.1 [8.02] 233 5.4*** [8.07] 190 3.8 [7.31] 193 6.8** [9.47] 195 8.5*** [10.00] General health Baseline, n Mean [SD] 224 31.7 [7.59] 231 31.7 [6.70] 234 30.4 [6.89] 190 33.6 [8.69] 193 32.9 [8.45] 196 33.4 [7.47] Week 8, n Mean [SD] 224 33.2 [8.46] 231 34.0 [8.56] 234 33.4 [8.18] 190 36.3 [9.17] 193 37.8 [10.50] 196 38.9 [10.40] Change at Week 8, n Mean [SD] 224 1.6 [6.30] 231 2.4 [6.51] 234 2.9 [6.54] 190 2.7 [7.20] 193 4.8* [8.79] 196 5.6*** [9.36] Vitality Baseline, n Mean [SD] 224 35.5 [9.21] 231 35.3 [8.28] 232 34.8 [8.29] 189 36.9 [9.15] 193 36.3 [9.13] 196 37.7 [9.57] Week 8, n Mean [SD] 224 38.8 [10.05] 231 39.7 [10.49] 232 39.8 [10.19] 189 40.7 [10.95] 193 43.4 [11.82] 196 45.2 [10.91] Change at Week 8, n Mean [SD] 224 3.3 [8.12] 231 4.5 [9.43] 232 5.0* [9.05] 189 3.8 [9.17] 193 7.2** [10.46] 196 7.6*** [10.32] Social functioning Baseline, n Mean [SD] 224 35.2 [10.04] 231 35.6 [9.57] 234 34.1 [9.41] 190 36.8 [10.50] 193 36.6 [10.18] 195 36.2 [9.95] Week 8, n Mean [SD] 224 38.2 [10.97] 231 39.0 [11.03] 234 40.0 [10.63] 190 40.2 [11.36] 193 43.2 [10.79] 195 44.1 [9.86] Change at Week 8, n Mean [SD] 224 3.0 [9.24] 231 3.5 [9.76] 234 5.9** [9.50] 190 3.4 [9.55] 193 6.6** [11.04] 195 7.9*** [11.11] Role-emotional Baseline, n Mean [SD] 223 38.9 [12.51] 231 38.5 [12.17] 234 37.7 [12.48] 190 38.5 [12.39] 193 38.4 [12.86] 195 38.7 [11.97] Week 8, n Mean [SD] 223 40.7 [12.53] 231 41.9 [13.09] 234 41.5 [12.74] 190 41.3 [12.34] 193 43.7 [11.85] 195 44.8 [10.78] Change at Week 8, n Mean [SD] 223 1.9 [10.72] 231 3.4 [10.84] 234 3.8 [11.30] 190 2.8 [10.80] 193 5.3* [10.47] 195 6.1** [12.34] Mental health Baseline, n Mean [SD] 224 40.5 [10.63] 231 39.5 [10.26] 232 38.8 [9.34] 189 38.6 [11.16] 193 38.8 [10.51] 196 39.6 [11.37] Week 8, n Mean [SD] 224 42.4 [11.35] 231 42.3 [11.49] 232 43.3 [10.24] 189 41.6 [11.94] 193 44.0 [11.32] 196 45.7 [11.00] Change at Week 8, n Mean [SD] 224 1.9 [8.17] 231 2.8 [9.34] 232 4.5** [8.59] 189 3.0 [8.56] 193 5.2* [10.29] 196 6.1*** [10.91] UNITI-1 UNITI-2 Patient-reportedoutcome Ustekinumab Ustekinumab Placebo 130 mg 6 mga Placebo 130 mg 6 mga IBDQ score, nb,c 247 245 249 209 209 209 Bowel symptoms  Baseline, n  Mean [SD] 245 38.6 [9.28] 244 38.2 [8.81] 248 38.5 [8.27] 207 38.8 [9.14] 209 38.2 [9.21] 208 38.9 [9.19]  Week 8, n  Mean [SD] 245 42.6 [10.31] 244 43.7 [11.27] 248 45.1 [10.01] 207 43.9 [11.02] 209 47.5[10.96] 208 50.6 [10.88]  Change at Week 8, n  Mean [SD] 245 4.0 [8.81] 244 5.5 [9.04] 248 6.6*** [8.56] 207 5.1 [8.78] 209 9.3*** [10.76] 208 11.7*** [11.21] Emotional functions  Baseline, n  Mean [SD] 245 46.5 [13.32] 243 47.0 [13.75] 248 45.9 [11.93] 207 46.7 [14.17] 209 44.3 [13.56] 208 46.8 [14.44]  Week 8, n  Mean [SD] 245 50.7 [14.99] 243 52.8 [16.06] 248 53.7 [14.20] 207 51.2 [15.71] 209 54.5 [15.28] 208 58.6 [14.43]  Change at Week 8, n  Mean [SD] 245 4.2 [10.52] 243 5.8 [11.53] 248 7.7*** [11.82] 207 4.5 [10.79] 209 10.1*** [13.95] 208 11.9*** [14.88] Systemic symptoms Baseline, n Mean [SD] 245 15.2 [5.25] 245 14.9 [4.74] 248 14.6 [4.97] 209 15.7 [5.35] 209 15.2 [5.11] 208 15.8 [5.23] Week 8, n Mean [SD] 245 17.3 [6.09] 245 18.3 [6.52] 248 18.5 [6.60] 209 18.5 [6.46] 209 20.0 [6.61] 208 21.8 [5.94] Change at Week 8, n Mean [SD] 245 2.1 [5.10] 245 3.4* [5.65] 248 3.9*** [5.57] 209 2.8 [5.17] 209 4.8*** [6.09] 208 6.0*** [6.29] Social functions Baseline Mean [SD] 244 19.8 [7.35] 244 19.3 [7.44] 248 19.2 [7.15] 209 21.5 [7.21] 208 20.4 [7.44] 209 21.4 [7.37] Week 8 n Mean [SD] 244 21.3 [8.09] 244 22.6 [8.23] 248 23.0 [7.99] 209 23.8 [7.75] 208 25.2 [7.65] 209 26.9 [6.97] Change at Week 8, n, Mean [SD] 244 1.5 [6.03] 244 3.3** [6.14] 248 3.8*** [6.63] 209 2.3 [5.67] 208 4.8*** [6.69] 209 5.6*** [7.12] SF-36 Score, n=b,c 225 231 235 190 194 196 Physical functioning Baseline, n Mean [SD] 224 44.2 [8.52] 231 44.3 [8.61] 234 43.5 [8.70] 190 44.9 [9.57] 193 44.2 [9.38] 196 43.7 [9.13] Week 8, n Mean [SD] 224 45.9 [8.67] 231 46.7 [9.23] 234 45.9 [9.52] 190 46.6 [9.21] 193 47.9 [8.45] 196 47.9 [8.65] Change at Week 8, n Mean [SD] 224 1.7 [6.58] 231 2.4 [6.76] 234 2.4 [7.27] 190 1.8 [6.68] 193 3.7* [7.36] 196 4.2** [7.09] Role-physical Baseline, n Mean [SD] 223 35.2 [8.87] 231 35.5 [9.51] 234 34.7 [9.45] 190 37.7 [9.36] 193 37.2 [9.92] 195 37.1 [9.64] Week 8, n Mean [SD] 223 39.1 [10.09] 231 39.6 [10.95] 234 39.7 [11.17] 190 40.8 [10.30] 193 43.3 [10.36] 195 44.3 [10.07] Change at Week 8, n Mean [SD] 223 3.9 [8.70] 231 4.1 [8.95] 234 5.0 [9.51] 190 3.1 [7.67] 193 6.1*** [8.60] 195 7.2*** [9.87] Bodily pain Baseline, n Mean [SD] 224 37.8 [8.11] 231 36.3 [7.03] 233 36.3 [7.72] 190 36.8 [7.27] 193 36.6 [8.20] 195 37.3 [7.27] Week 8, n Mean [SD] 224 40.3 [9.09] 231 40.5 [8.87] 233 41.7 [9.20] 190 40.6 [8.91] 193 43.3 [9.61] 195 45.8 [9.04] Change at Week 8, n Mean [SD] 224 2.5 [7.75] 231 4.1 [8.02] 233 5.4*** [8.07] 190 3.8 [7.31] 193 6.8** [9.47] 195 8.5*** [10.00] General health Baseline, n Mean [SD] 224 31.7 [7.59] 231 31.7 [6.70] 234 30.4 [6.89] 190 33.6 [8.69] 193 32.9 [8.45] 196 33.4 [7.47] Week 8, n Mean [SD] 224 33.2 [8.46] 231 34.0 [8.56] 234 33.4 [8.18] 190 36.3 [9.17] 193 37.8 [10.50] 196 38.9 [10.40] Change at Week 8, n Mean [SD] 224 1.6 [6.30] 231 2.4 [6.51] 234 2.9 [6.54] 190 2.7 [7.20] 193 4.8* [8.79] 196 5.6*** [9.36] Vitality Baseline, n Mean [SD] 224 35.5 [9.21] 231 35.3 [8.28] 232 34.8 [8.29] 189 36.9 [9.15] 193 36.3 [9.13] 196 37.7 [9.57] Week 8, n Mean [SD] 224 38.8 [10.05] 231 39.7 [10.49] 232 39.8 [10.19] 189 40.7 [10.95] 193 43.4 [11.82] 196 45.2 [10.91] Change at Week 8, n Mean [SD] 224 3.3 [8.12] 231 4.5 [9.43] 232 5.0* [9.05] 189 3.8 [9.17] 193 7.2** [10.46] 196 7.6*** [10.32] Social functioning Baseline, n Mean [SD] 224 35.2 [10.04] 231 35.6 [9.57] 234 34.1 [9.41] 190 36.8 [10.50] 193 36.6 [10.18] 195 36.2 [9.95] Week 8, n Mean [SD] 224 38.2 [10.97] 231 39.0 [11.03] 234 40.0 [10.63] 190 40.2 [11.36] 193 43.2 [10.79] 195 44.1 [9.86] Change at Week 8, n Mean [SD] 224 3.0 [9.24] 231 3.5 [9.76] 234 5.9** [9.50] 190 3.4 [9.55] 193 6.6** [11.04] 195 7.9*** [11.11] Role-emotional Baseline, n Mean [SD] 223 38.9 [12.51] 231 38.5 [12.17] 234 37.7 [12.48] 190 38.5 [12.39] 193 38.4 [12.86] 195 38.7 [11.97] Week 8, n Mean [SD] 223 40.7 [12.53] 231 41.9 [13.09] 234 41.5 [12.74] 190 41.3 [12.34] 193 43.7 [11.85] 195 44.8 [10.78] Change at Week 8, n Mean [SD] 223 1.9 [10.72] 231 3.4 [10.84] 234 3.8 [11.30] 190 2.8 [10.80] 193 5.3* [10.47] 195 6.1** [12.34] Mental health Baseline, n Mean [SD] 224 40.5 [10.63] 231 39.5 [10.26] 232 38.8 [9.34] 189 38.6 [11.16] 193 38.8 [10.51] 196 39.6 [11.37] Week 8, n Mean [SD] 224 42.4 [11.35] 231 42.3 [11.49] 232 43.3 [10.24] 189 41.6 [11.94] 193 44.0 [11.32] 196 45.7 [11.00] Change at Week 8, n Mean [SD] 224 1.9 [8.17] 231 2.8 [9.34] 232 4.5** [8.59] 189 3.0 [8.56] 193 5.2* [10.29] 196 6.1*** [10.91] IBDQ, Inflammatory Bowel Disease Questionnaire; SD, standard deviation; SF-36, 36-Item Short Form Health Survey. aWeight-range based ustekinumab doses approximating 6 mg/kg: 260 mg [weight ≤55 kg], 390 mg [weight >55 kg and ≤85 kg], 520 mg [weight >85 kg]. bPatients who had a prohibited Crohn’s disease-related surgery or had prohibited concomitant medication changes before Week 8 had their baseline value carried forward. cPatients who had insufficient data at Week 8 had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large With both ustekinumab doses in both studies, significantly greater proportions of patients experienced clinically meaningful improvement in IBDQ at Week 8 [UNITI-1: 54.8% and 46.9%, respectively, versus 36.5%; p <0.001 and p = 0.019, respectively; UNITI-2: 68.1% and 58.7%, respectively, versus 41.1%; p <0.001 and p <0.001, respectively; Figure 2A, B]. All patients had impaired baseline IBDQ scores [<210 points]. In both ustekinumab dose groups at Week 8, a greater proportion of patients had normal scores [≥210 points] than placebo [Figure 2A, B]. In UNITI-2, this comparison was only statistically significant for the comparison of ustekinumab 6 mg/kg with placebo [5.8% versus 1.4%, p = 0.019]. 3.1.2. SF-36 results In both studies, the mean baseline SF-36, PCS, and MCS scores were similar among the three treatment groups [Table 1; Figure 1C-F]. In UNITI-1 at Week 8, the mean change from baseline in the PCS score was numerically, but not significantly, greater in the both ustekinumab dose groups compared with the placebo group. The mean change from baseline in the MCS score at that time was significantly greater in the ustekinumab 6 mg/kg group [p = 0.006], but only numerically greater for the ustekinumab 130 mg group compared with the placebo group. In UNITI-2, the mean changes from baseline in the MCS and PCS scores were significantly greater for both ustekinumab groups compared with the placebo group [p <0.05 for all comparisons; Table 1]. In UNITI-1, mean changes from baseline in norm-based scores of the SF-36 scales at Week 8 were numerically greater in both ustekinumab groups compared with placebo; however, the ustekinumab 6 mg/kg group showed relatively greater differences, with statistically significant differences observed for bodily pain, vitality, social functioning, and mental health scales [Table 2]. In UNITI-2, the mean changes from baseline in norm-based scores of the SF-36 scales at Week 8 were significantly greater in both ustekinumab groups compared with the placebo group [p <0.05 for all comparisons; Table 2]. In UNITI-2, the proportion of patients with a clinically meaningful improvement in PCS was significantly greater for the ustekinumab 6 mg/kg and 130 mg groups than for the placebo group [49.2% and 44.0%, respectively versus 31.2%; p <0.001 and p = 0.009, respectively]. More patients experienced clinically significant improvement in MCS in both the ustekinumab 6 mg/kg and 130 mg groups than the placebo group [51.3% and 49.2%, respectively, versus 38.6%; p = 0.014 and p = 0.036, respectively]. In UNITI-1, MCS scores were only significantly greater for the ustekinumab 6 mg/kg group in comparison with the placebo group [42.4% versus 30.0%; p = 0.007] [Figure 2A, B]. For patients with impaired SF-36 scores at baseline, defined as less than the US population norm of 50 points, greater proportions of patients receiving either ustekinumab dose had normal MCS and PCS scores compared with placebo at Week 8 [Figure 2A, B]. These differences were statistically significant in UNITI-2 for the MCS [with both ustekinumab doses] and for the PCS in the ustekinumab 6 mg/kg group. Figure 2. View largeDownload slide Proportions of patients at Week 8 who achieved ≥16-point improvement in or normalised [≥210] IBDQ total scores and proportions of patients who achieved ≥5-point improvement in or normalized [≥50] SF-36 MCS and PCS scores with induction therapy. IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, Mental Component Summary Score; NS, not statistically significant; PCS, Physical Component Summary Score; SF-36, 36-item Short Form Health Survey. Figure 2. View largeDownload slide Proportions of patients at Week 8 who achieved ≥16-point improvement in or normalised [≥210] IBDQ total scores and proportions of patients who achieved ≥5-point improvement in or normalized [≥50] SF-36 MCS and PCS scores with induction therapy. IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, Mental Component Summary Score; NS, not statistically significant; PCS, Physical Component Summary Score; SF-36, 36-item Short Form Health Survey. 3.2. Maintenance study 3.2.1. IBDQ results At baseline of the maintenance study [induction Week 8], the mean [SD] IBDQ scores for randomised ustekinumab responders were generally similar among the placebo and ustekinumab q12w and q8w groups (163.6 [31.75], 165.8 [32.82], and 170.5 [29.33], respectively) [Table 3; Figure 3A]. At Week 20, the mean decrease [worsening] in IBDQ score from maintenance baseline was significantly less in the ustekinumab 90 mg q12w group and numerically less in the ustekinumab q8w dose group compared with the placebo group [p = 0.035 and p = 0.183, respectively; Table 3]. At Week 44, the mean decreases in IBDQ scores from maintenance baseline were significantly less in the ustekinumab q12w and q8w dose groups (-8.9 [43.08] versus -9.9 [34.83], respectively) compared with the placebo group (-21.5 [39.26]; p < 0.001 and p = 0.003, respectively; Table 3; Figure 3A]. These results indicate that patients who received ustekinumab were more likely to maintain the improvement in their IBDQ scores achieved during induction compared with patients who discontinued ustekinumab treatment. Table 3. Mean [SD] and mean change [SD] from baseline in the IBDQ score at Week 20 and Week 44 of maintenance therapy. Ustekinumab Placebo SCa [n = 131] 90 mg SC q12w [n = 129] 90 mg SC q8w [n = 128] Baseline, n 130 129 126  Mean [SD] 163.6 [31.76] 165.8 [32.82] 170.5 [29.33] Week 20, n 130 129 126  Mean [SD] 150.8 [40.99] 159.6 [40.96] 161.6 [40.27] Change from baseline Week 20b,c, n 130 129 126  Mean [SD] -12.8 [34.05] -6.3 [37.04]* -8.9 [31.46] Week 44, n 130 128 126  Mean [SD] 142.1 [42.46] 156.9 [43.54] 160.5 [40.71] Change from baseline Week 44b,c, n 130 128 126  Mean [SD] -21.5 [39.26] -8.9 [43.08]*** -9.9 [34.83]** Ustekinumab Placebo SCa [n = 131] 90 mg SC q12w [n = 129] 90 mg SC q8w [n = 128] Baseline, n 130 129 126  Mean [SD] 163.6 [31.76] 165.8 [32.82] 170.5 [29.33] Week 20, n 130 129 126  Mean [SD] 150.8 [40.99] 159.6 [40.96] 161.6 [40.27] Change from baseline Week 20b,c, n 130 129 126  Mean [SD] -12.8 [34.05] -6.3 [37.04]* -8.9 [31.46] Week 44, n 130 128 126  Mean [SD] 142.1 [42.46] 156.9 [43.54] 160.5 [40.71] Change from baseline Week 44b,c, n 130 128 126  Mean [SD] -21.5 [39.26] -8.9 [43.08]*** -9.9 [34.83]** IBDQ, inflammatory bowel disease questionnaire; IV, intravenous; SC, subcutaneous; SD, standard deviation; q8w, every 8 weeks; q12w, every 12 weeks. aPatients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study. bPatients who had a prohibited Crohn’s disease-related surgery, had a loss of response, had prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be worsened Crohn’s disease before the designated analysis timepoint had their induction baseline value carried forward. cPatients who had insufficient data at the designated analysis timepoint had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Table 3. Mean [SD] and mean change [SD] from baseline in the IBDQ score at Week 20 and Week 44 of maintenance therapy. Ustekinumab Placebo SCa [n = 131] 90 mg SC q12w [n = 129] 90 mg SC q8w [n = 128] Baseline, n 130 129 126  Mean [SD] 163.6 [31.76] 165.8 [32.82] 170.5 [29.33] Week 20, n 130 129 126  Mean [SD] 150.8 [40.99] 159.6 [40.96] 161.6 [40.27] Change from baseline Week 20b,c, n 130 129 126  Mean [SD] -12.8 [34.05] -6.3 [37.04]* -8.9 [31.46] Week 44, n 130 128 126  Mean [SD] 142.1 [42.46] 156.9 [43.54] 160.5 [40.71] Change from baseline Week 44b,c, n 130 128 126  Mean [SD] -21.5 [39.26] -8.9 [43.08]*** -9.9 [34.83]** Ustekinumab Placebo SCa [n = 131] 90 mg SC q12w [n = 129] 90 mg SC q8w [n = 128] Baseline, n 130 129 126  Mean [SD] 163.6 [31.76] 165.8 [32.82] 170.5 [29.33] Week 20, n 130 129 126  Mean [SD] 150.8 [40.99] 159.6 [40.96] 161.6 [40.27] Change from baseline Week 20b,c, n 130 129 126  Mean [SD] -12.8 [34.05] -6.3 [37.04]* -8.9 [31.46] Week 44, n 130 128 126  Mean [SD] 142.1 [42.46] 156.9 [43.54] 160.5 [40.71] Change from baseline Week 44b,c, n 130 128 126  Mean [SD] -21.5 [39.26] -8.9 [43.08]*** -9.9 [34.83]** IBDQ, inflammatory bowel disease questionnaire; IV, intravenous; SC, subcutaneous; SD, standard deviation; q8w, every 8 weeks; q12w, every 12 weeks. aPatients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study. bPatients who had a prohibited Crohn’s disease-related surgery, had a loss of response, had prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be worsened Crohn’s disease before the designated analysis timepoint had their induction baseline value carried forward. cPatients who had insufficient data at the designated analysis timepoint had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Figure 3. View largeDownload slide Mean and mean change from baseline, Week 20, and Week 44 in IBDQ [A], PCS [B] and MCS [C] scores with maintenance therapy. Figure 3. View largeDownload slide Mean and mean change from baseline, Week 20, and Week 44 in IBDQ [A], PCS [B] and MCS [C] scores with maintenance therapy. The proportion of patients with a clinically meaningful improvement in IBDQ score at Week 44 was significantly greater than placebo for the ustekinumab q8w dose but not for the ustekinumab q12w dose group [67.9% and 61.3%, respectively, versus placebo 50.4%; p = 0.014 and p = 0.140, respectively; Figure 4]. Among patients with IBDQ scores of <210 points at baseline of an induction study, greater proportions of patients receiving either ustekinumab dose, than placebo, achieved normal scores at Week 44 following maintenance treatment [Figure 4]. Figure 4. View largeDownload slide Proportions of patients at Week 44 who achieved ≥16-point improvement in or normalised [≥210] IBDQ total score and proportions of patients who achieved ≥5-point improvement in or normalised [≥50] SF-36 PCS and MCS scores from the baseline of an induction study. IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, Mental Component Summary Score; NS, not statistically significant; PCS, Physical Component Summary Score; q8w, every 8 weeks; q12w, every 12 weeks. SF-36, 36-item Short Form Health Survey. Figure 4. View largeDownload slide Proportions of patients at Week 44 who achieved ≥16-point improvement in or normalised [≥210] IBDQ total score and proportions of patients who achieved ≥5-point improvement in or normalised [≥50] SF-36 PCS and MCS scores from the baseline of an induction study. IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, Mental Component Summary Score; NS, not statistically significant; PCS, Physical Component Summary Score; q8w, every 8 weeks; q12w, every 12 weeks. SF-36, 36-item Short Form Health Survey. 3.2.2. SF-36 results The mean PCS and MCS scores of the SF-36 at baseline of maintenance [induction Week 8] were similar among the three treatment groups [Table 4; Figure 3B, C]. For the ustekinumab q8w group, the mean decreases from baseline [worsening] of the maintenance study in the PCS and MCS scores were significantly less at Week 44 compared with the placebo group [Table 4]. For the ustekinumab q12w group, only the mean decrease from baseline during maintenance in the MCS score at Week 44 was significantly less compared with the placebo group. Table 4. Mean [SD] and mean change [SD] from baseline in the physical and mental component summary scores of the SF-36 at Week 20 and Week 44 of maintenance therapy. Ustekinumab SF-36 Component Summary Scores Placebo SCa [n = 122] 90 mg SC q12w [n= 121] 90 mg SC q8w [n= 121] Physical Component Summary Baseline, n 122 121 121  Mean [SD] 46.3 [8.21] 47.1 [8.10] 47.4 [7.52] Week 20b,c, n 122 121 121  Mean [SD] 44.6 [9.71] 45.4 [8.86] 46.8 [9.08] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -1.7 [7.67] -1.7 [7.18] -0.6 [6.37] Week 44b,c, n 122 120 121  Mean [SD] 42.7 [9.96] 44.9 [9.62] 46.5 [8.98] Change from baseline Week 44b,c, n 122 120 121  Mean [SD] -3.6 [9.33] -2.3 [9.31] -0.9 [7.14]** Mental component summary Baseline, n 122 121 121  Mean [SD] 45.7 [10.89] 46.4 [10.66] 47.3 [9.91] Week 20b,c, n 122 121 121  Mean [SD] 43.0 [11.34] 45.1 [11.40] 45.6 [10.57] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -2.7 [10.78] -1.3 [11.53] -1.7 [9.01] Week 44b,c, n 122 120 121  Mean [SD] 41.3 [11.79] 44.6 [11.81] 45.6 [11.22] Change from baseline Week 44b,c., n 122 120 121  Mean [SD] -4.4 [11.06] -1.9 [12.68]* -1.7 [9.76]** Ustekinumab SF-36 Component Summary Scores Placebo SCa [n = 122] 90 mg SC q12w [n= 121] 90 mg SC q8w [n= 121] Physical Component Summary Baseline, n 122 121 121  Mean [SD] 46.3 [8.21] 47.1 [8.10] 47.4 [7.52] Week 20b,c, n 122 121 121  Mean [SD] 44.6 [9.71] 45.4 [8.86] 46.8 [9.08] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -1.7 [7.67] -1.7 [7.18] -0.6 [6.37] Week 44b,c, n 122 120 121  Mean [SD] 42.7 [9.96] 44.9 [9.62] 46.5 [8.98] Change from baseline Week 44b,c, n 122 120 121  Mean [SD] -3.6 [9.33] -2.3 [9.31] -0.9 [7.14]** Mental component summary Baseline, n 122 121 121  Mean [SD] 45.7 [10.89] 46.4 [10.66] 47.3 [9.91] Week 20b,c, n 122 121 121  Mean [SD] 43.0 [11.34] 45.1 [11.40] 45.6 [10.57] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -2.7 [10.78] -1.3 [11.53] -1.7 [9.01] Week 44b,c, n 122 120 121  Mean [SD] 41.3 [11.79] 44.6 [11.81] 45.6 [11.22] Change from baseline Week 44b,c., n 122 120 121  Mean [SD] -4.4 [11.06] -1.9 [12.68]* -1.7 [9.76]** IV, intravenous; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous; SD, standard deviation; SF-36, 36-item Short-Form Health Survey. aPatients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study. bPatients who had a prohibited Crohn’s disease-related surgery, had a loss of response, had prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be worsened Crohn’s disease before the designated analysis timepoint had their induction baseline value carried forward. cPatients who had insufficient data at the designated analysis timepoint had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Table 4. Mean [SD] and mean change [SD] from baseline in the physical and mental component summary scores of the SF-36 at Week 20 and Week 44 of maintenance therapy. Ustekinumab SF-36 Component Summary Scores Placebo SCa [n = 122] 90 mg SC q12w [n= 121] 90 mg SC q8w [n= 121] Physical Component Summary Baseline, n 122 121 121  Mean [SD] 46.3 [8.21] 47.1 [8.10] 47.4 [7.52] Week 20b,c, n 122 121 121  Mean [SD] 44.6 [9.71] 45.4 [8.86] 46.8 [9.08] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -1.7 [7.67] -1.7 [7.18] -0.6 [6.37] Week 44b,c, n 122 120 121  Mean [SD] 42.7 [9.96] 44.9 [9.62] 46.5 [8.98] Change from baseline Week 44b,c, n 122 120 121  Mean [SD] -3.6 [9.33] -2.3 [9.31] -0.9 [7.14]** Mental component summary Baseline, n 122 121 121  Mean [SD] 45.7 [10.89] 46.4 [10.66] 47.3 [9.91] Week 20b,c, n 122 121 121  Mean [SD] 43.0 [11.34] 45.1 [11.40] 45.6 [10.57] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -2.7 [10.78] -1.3 [11.53] -1.7 [9.01] Week 44b,c, n 122 120 121  Mean [SD] 41.3 [11.79] 44.6 [11.81] 45.6 [11.22] Change from baseline Week 44b,c., n 122 120 121  Mean [SD] -4.4 [11.06] -1.9 [12.68]* -1.7 [9.76]** Ustekinumab SF-36 Component Summary Scores Placebo SCa [n = 122] 90 mg SC q12w [n= 121] 90 mg SC q8w [n= 121] Physical Component Summary Baseline, n 122 121 121  Mean [SD] 46.3 [8.21] 47.1 [8.10] 47.4 [7.52] Week 20b,c, n 122 121 121  Mean [SD] 44.6 [9.71] 45.4 [8.86] 46.8 [9.08] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -1.7 [7.67] -1.7 [7.18] -0.6 [6.37] Week 44b,c, n 122 120 121  Mean [SD] 42.7 [9.96] 44.9 [9.62] 46.5 [8.98] Change from baseline Week 44b,c, n 122 120 121  Mean [SD] -3.6 [9.33] -2.3 [9.31] -0.9 [7.14]** Mental component summary Baseline, n 122 121 121  Mean [SD] 45.7 [10.89] 46.4 [10.66] 47.3 [9.91] Week 20b,c, n 122 121 121  Mean [SD] 43.0 [11.34] 45.1 [11.40] 45.6 [10.57] Change from baseline Week 20b,c, n 122 121 121  Mean [SD] -2.7 [10.78] -1.3 [11.53] -1.7 [9.01] Week 44b,c, n 122 120 121  Mean [SD] 41.3 [11.79] 44.6 [11.81] 45.6 [11.22] Change from baseline Week 44b,c., n 122 120 121  Mean [SD] -4.4 [11.06] -1.9 [12.68]* -1.7 [9.76]** IV, intravenous; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous; SD, standard deviation; SF-36, 36-item Short-Form Health Survey. aPatients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study. bPatients who had a prohibited Crohn’s disease-related surgery, had a loss of response, had prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be worsened Crohn’s disease before the designated analysis timepoint had their induction baseline value carried forward. cPatients who had insufficient data at the designated analysis timepoint had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large For the SF-36 PCS and MCS scores, both the ustekinumab q8w and q12w dose groups had significantly greater proportions of patients with a clinically meaningful [≥5-point] improvement, except for the PCS in the ustekinumab q12w group [Figure 4]. A significantly greater proportion of patients in the ustekinumab q8w group achieved clinically-meaningful improvement in PCS than in the placebo group [52.1% versus placebo, 34.7%; p = 0.008], and a significantly greater proportion of patients in the ustekinumab q8w and q12w dose groups achieved a clinically meaningful improvement in MCS than the placebo group at Week 44 [47.9% and 46.7%, respectively, versus placebo, 28.9%; p = 0.003 and p = 0.005, respectively; Figure 4]. For patients with baseline SF-36 scores lower than the US population norm, greater proportions of patients in both ustekinumab dose groups had normal MCS and PCS scores at Week 44 [Figure 4]. These results were significantly greater with ustekinumab q8w for both MCS and PCS. The mean SF-36 dimension scores [i.e. physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health] were generally consistent across all groups at baseline of the maintenance study. At Week 44, the mean worsening from baseline in the SF-36 dimension scores was generally less in the ustekinumab q12w and q8w groups compared with the placebo group [Table 5]. Specifically, the mean decreases [worsening] in general health, vitality, and mental health dimension scores in the ustekinumab q12w group were significantly less than those observed in the placebo group at Week 44, whereas the mean worsening in six of the eight dimension scores [physical functioning, role-physical, bodily pain, vitality, social functioning, and mental health] in the ustekinumab q8w group were significantly less than those observed for the placebo group at Week 44. Table 5. Mean [SD] and mean change [SD] from baseline in IBDQ and SF-36 dimension and scale scores at Week 44 of maintenance therapy. Ustekinumab Patient-reported outcome Placebo SCa 90 mg SC q12w 90 mg SC q8w IBDQb,c 131 129 128 Bowel symptoms Baseline, n Mean [SD] 131 52.2 [9.86] 129 53.7 [8.93] 128 54.0 [8.92] Week 44, n Mean [SD] 131 45.5 [12.70] 128 50.4 [13.48] 127 51.4 [12.63] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.7 [11.62] -3.3** [12.26] -3.0*** [11.06] Emotional functions Baseline, n Mean [SD] 131 60.4 [13.39] 129 61.1 [14.52] 127 62.8 [12.44] Week 44, n Mean [SD] 131 53.8 [16.26] 128 58.6 [17.05] 127 59.9 [15.99] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.6 [15.76] -2.6** [17.46] -2.9** [13.42] Systemic symptoms Baseline, n Mean [SD] 130 23.1 [5.79] 129 23.2 [6.04] 128 23.9 [5.55] Week 44, n Mean [SD] 130 18.9 [7.78] 128 20.9 [7.41] 128 21.9 [7.14] Change from baseline Week 44, n 130 128 128 Mean [SD] -4.2 [7.42] -2.3* [7.77] -2.0** [6.19] Social functions Baseline, n Mean [SD] 131 27.8 [6.31] 129 27.9 [7.18] 127 28.8 [6.25] Week 44, n Mean [SD] 131 24.1 [8.98] 128 27.1 [8.20] 127 27.0 [7.80] Change from baseline Week 44, n 131 128 127 Mean [SD] -3.7 [7.67] -0.8*** [8.49] -1.8* [7.38] SF-36b,c 122 121 121 Physical functioning Baseline, n Mean [SD] 122 49.8 [7.70] 121 50.4 [8.51] 121 51.0 [7.33] Week 44, n Mean [SD] 122 46.7 [9.35] 121 48.5 [9.67] 121 50.6 [7.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.2 [8.42] -1.9 [7.94] -0.4** [5.63] Role-physical Baseline, n Mean [SD] 122 45.6 [9.75] 121 46.3 [9.93] 121 47.6 [9.37] Week 44, n Mean [SD] 122 40.8 [12.01] 121 43.4 [11.89] 121 46.0 [10.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.8 [11.87] -2.9 [12.73] -1.6** [8.79] Bodily pain Baseline, n Mean [SD] 122 47.1 [8.04] 121 48.8 [8.17] 121 48.2 [8.67] Week 44, n Mean [SD] 122 42.1 [10.65] 120 45.1 [11.34] 121 46.5 [10.97] Change from baseline Week 44, n 122 120 121 Mean [SD] -5.0 [10.61] -3.8 [11.73] -1.7** [8.87] General health Baseline, n Mean [SD] 122 39.5 [10.37] 121 40.0 [10.54] 121 40.7 [10.06] Week 44, n Mean [SD] 122 37.2 [10.94] 121 39.9 [11.31] 121 40.1 [11.03] Change from baseline Week 44, n 122 121 121 Mean [SD] -2.3 [10.18] -0.1* [10.25] -0.6 [8.78] Vitality Baseline, n Mean [SD]Week 44, n Mean [SD]Change from baseline Week 44, nMean [SD] 122 46.4 [10.27]122 41.4 [12.25]122-5.0 [11.77] 121 47.2 [10.82]120 44.8 [12.83]120-2.4* [12.42] 121 48.6 [10.94]121 45.6 [12.45]121-2.9* [10.38] Social functioning Baseline, n Mean [SD] 122 45.7 [8.89] 121 46.4 [10.17] 121 46.5 [9.54] Week 44, n Mean [SD] 122 41.5 [11.79] 121 44.1 [11.76] 121 45.3 [10.96] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.2 [12.23] -2.3 [13.41] -1.2* [10.06] Role-emotional Baseline, n Mean [SD] 122 45.5 [11.95] 121 46.4 [10.90] 121 47.9 [9.64] Week 44, n Mean [SD] 122 42.2 [13.46] 121 44.6 [12.80] 121 46.5 [11.69] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.3 [11.59] -1.8 [14.04] -1.4 [9.29] Mental health Baseline, n Mean [SD] 122 46.9 [10.68] 121 47.7 [10.11] 121 48.1 [10.30] Week 44, n Mean [SD] 122 42.0 [10.98] 120 45.6 [11.57] 121 47.0 [10.81] Change from baseline Week 44, n 122 120 121 Mean [SD] -4.9 [10.52] -2.3** [11.93] -1.1*** [9.85] Ustekinumab Patient-reported outcome Placebo SCa 90 mg SC q12w 90 mg SC q8w IBDQb,c 131 129 128 Bowel symptoms Baseline, n Mean [SD] 131 52.2 [9.86] 129 53.7 [8.93] 128 54.0 [8.92] Week 44, n Mean [SD] 131 45.5 [12.70] 128 50.4 [13.48] 127 51.4 [12.63] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.7 [11.62] -3.3** [12.26] -3.0*** [11.06] Emotional functions Baseline, n Mean [SD] 131 60.4 [13.39] 129 61.1 [14.52] 127 62.8 [12.44] Week 44, n Mean [SD] 131 53.8 [16.26] 128 58.6 [17.05] 127 59.9 [15.99] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.6 [15.76] -2.6** [17.46] -2.9** [13.42] Systemic symptoms Baseline, n Mean [SD] 130 23.1 [5.79] 129 23.2 [6.04] 128 23.9 [5.55] Week 44, n Mean [SD] 130 18.9 [7.78] 128 20.9 [7.41] 128 21.9 [7.14] Change from baseline Week 44, n 130 128 128 Mean [SD] -4.2 [7.42] -2.3* [7.77] -2.0** [6.19] Social functions Baseline, n Mean [SD] 131 27.8 [6.31] 129 27.9 [7.18] 127 28.8 [6.25] Week 44, n Mean [SD] 131 24.1 [8.98] 128 27.1 [8.20] 127 27.0 [7.80] Change from baseline Week 44, n 131 128 127 Mean [SD] -3.7 [7.67] -0.8*** [8.49] -1.8* [7.38] SF-36b,c 122 121 121 Physical functioning Baseline, n Mean [SD] 122 49.8 [7.70] 121 50.4 [8.51] 121 51.0 [7.33] Week 44, n Mean [SD] 122 46.7 [9.35] 121 48.5 [9.67] 121 50.6 [7.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.2 [8.42] -1.9 [7.94] -0.4** [5.63] Role-physical Baseline, n Mean [SD] 122 45.6 [9.75] 121 46.3 [9.93] 121 47.6 [9.37] Week 44, n Mean [SD] 122 40.8 [12.01] 121 43.4 [11.89] 121 46.0 [10.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.8 [11.87] -2.9 [12.73] -1.6** [8.79] Bodily pain Baseline, n Mean [SD] 122 47.1 [8.04] 121 48.8 [8.17] 121 48.2 [8.67] Week 44, n Mean [SD] 122 42.1 [10.65] 120 45.1 [11.34] 121 46.5 [10.97] Change from baseline Week 44, n 122 120 121 Mean [SD] -5.0 [10.61] -3.8 [11.73] -1.7** [8.87] General health Baseline, n Mean [SD] 122 39.5 [10.37] 121 40.0 [10.54] 121 40.7 [10.06] Week 44, n Mean [SD] 122 37.2 [10.94] 121 39.9 [11.31] 121 40.1 [11.03] Change from baseline Week 44, n 122 121 121 Mean [SD] -2.3 [10.18] -0.1* [10.25] -0.6 [8.78] Vitality Baseline, n Mean [SD]Week 44, n Mean [SD]Change from baseline Week 44, nMean [SD] 122 46.4 [10.27]122 41.4 [12.25]122-5.0 [11.77] 121 47.2 [10.82]120 44.8 [12.83]120-2.4* [12.42] 121 48.6 [10.94]121 45.6 [12.45]121-2.9* [10.38] Social functioning Baseline, n Mean [SD] 122 45.7 [8.89] 121 46.4 [10.17] 121 46.5 [9.54] Week 44, n Mean [SD] 122 41.5 [11.79] 121 44.1 [11.76] 121 45.3 [10.96] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.2 [12.23] -2.3 [13.41] -1.2* [10.06] Role-emotional Baseline, n Mean [SD] 122 45.5 [11.95] 121 46.4 [10.90] 121 47.9 [9.64] Week 44, n Mean [SD] 122 42.2 [13.46] 121 44.6 [12.80] 121 46.5 [11.69] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.3 [11.59] -1.8 [14.04] -1.4 [9.29] Mental health Baseline, n Mean [SD] 122 46.9 [10.68] 121 47.7 [10.11] 121 48.1 [10.30] Week 44, n Mean [SD] 122 42.0 [10.98] 120 45.6 [11.57] 121 47.0 [10.81] Change from baseline Week 44, n 122 120 121 Mean [SD] -4.9 [10.52] -2.3** [11.93] -1.1*** [9.85] IBDQ, Inflammatory Bowel Disease Questionnaire; IV, intravenous; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous; SD, standard deviation; SF-36, 36-Item Short Form Health Survey. aPatients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study. bPatients who had a prohibited Crohn’s disease-related surgery, had a loss of response, had prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be worsened Crohn’s disease before the designated analysis timepoint had their induction baseline value carried forward. cPatients who had insufficient data at the designated analysis timepoint had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large Table 5. Mean [SD] and mean change [SD] from baseline in IBDQ and SF-36 dimension and scale scores at Week 44 of maintenance therapy. Ustekinumab Patient-reported outcome Placebo SCa 90 mg SC q12w 90 mg SC q8w IBDQb,c 131 129 128 Bowel symptoms Baseline, n Mean [SD] 131 52.2 [9.86] 129 53.7 [8.93] 128 54.0 [8.92] Week 44, n Mean [SD] 131 45.5 [12.70] 128 50.4 [13.48] 127 51.4 [12.63] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.7 [11.62] -3.3** [12.26] -3.0*** [11.06] Emotional functions Baseline, n Mean [SD] 131 60.4 [13.39] 129 61.1 [14.52] 127 62.8 [12.44] Week 44, n Mean [SD] 131 53.8 [16.26] 128 58.6 [17.05] 127 59.9 [15.99] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.6 [15.76] -2.6** [17.46] -2.9** [13.42] Systemic symptoms Baseline, n Mean [SD] 130 23.1 [5.79] 129 23.2 [6.04] 128 23.9 [5.55] Week 44, n Mean [SD] 130 18.9 [7.78] 128 20.9 [7.41] 128 21.9 [7.14] Change from baseline Week 44, n 130 128 128 Mean [SD] -4.2 [7.42] -2.3* [7.77] -2.0** [6.19] Social functions Baseline, n Mean [SD] 131 27.8 [6.31] 129 27.9 [7.18] 127 28.8 [6.25] Week 44, n Mean [SD] 131 24.1 [8.98] 128 27.1 [8.20] 127 27.0 [7.80] Change from baseline Week 44, n 131 128 127 Mean [SD] -3.7 [7.67] -0.8*** [8.49] -1.8* [7.38] SF-36b,c 122 121 121 Physical functioning Baseline, n Mean [SD] 122 49.8 [7.70] 121 50.4 [8.51] 121 51.0 [7.33] Week 44, n Mean [SD] 122 46.7 [9.35] 121 48.5 [9.67] 121 50.6 [7.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.2 [8.42] -1.9 [7.94] -0.4** [5.63] Role-physical Baseline, n Mean [SD] 122 45.6 [9.75] 121 46.3 [9.93] 121 47.6 [9.37] Week 44, n Mean [SD] 122 40.8 [12.01] 121 43.4 [11.89] 121 46.0 [10.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.8 [11.87] -2.9 [12.73] -1.6** [8.79] Bodily pain Baseline, n Mean [SD] 122 47.1 [8.04] 121 48.8 [8.17] 121 48.2 [8.67] Week 44, n Mean [SD] 122 42.1 [10.65] 120 45.1 [11.34] 121 46.5 [10.97] Change from baseline Week 44, n 122 120 121 Mean [SD] -5.0 [10.61] -3.8 [11.73] -1.7** [8.87] General health Baseline, n Mean [SD] 122 39.5 [10.37] 121 40.0 [10.54] 121 40.7 [10.06] Week 44, n Mean [SD] 122 37.2 [10.94] 121 39.9 [11.31] 121 40.1 [11.03] Change from baseline Week 44, n 122 121 121 Mean [SD] -2.3 [10.18] -0.1* [10.25] -0.6 [8.78] Vitality Baseline, n Mean [SD]Week 44, n Mean [SD]Change from baseline Week 44, nMean [SD] 122 46.4 [10.27]122 41.4 [12.25]122-5.0 [11.77] 121 47.2 [10.82]120 44.8 [12.83]120-2.4* [12.42] 121 48.6 [10.94]121 45.6 [12.45]121-2.9* [10.38] Social functioning Baseline, n Mean [SD] 122 45.7 [8.89] 121 46.4 [10.17] 121 46.5 [9.54] Week 44, n Mean [SD] 122 41.5 [11.79] 121 44.1 [11.76] 121 45.3 [10.96] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.2 [12.23] -2.3 [13.41] -1.2* [10.06] Role-emotional Baseline, n Mean [SD] 122 45.5 [11.95] 121 46.4 [10.90] 121 47.9 [9.64] Week 44, n Mean [SD] 122 42.2 [13.46] 121 44.6 [12.80] 121 46.5 [11.69] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.3 [11.59] -1.8 [14.04] -1.4 [9.29] Mental health Baseline, n Mean [SD] 122 46.9 [10.68] 121 47.7 [10.11] 121 48.1 [10.30] Week 44, n Mean [SD] 122 42.0 [10.98] 120 45.6 [11.57] 121 47.0 [10.81] Change from baseline Week 44, n 122 120 121 Mean [SD] -4.9 [10.52] -2.3** [11.93] -1.1*** [9.85] Ustekinumab Patient-reported outcome Placebo SCa 90 mg SC q12w 90 mg SC q8w IBDQb,c 131 129 128 Bowel symptoms Baseline, n Mean [SD] 131 52.2 [9.86] 129 53.7 [8.93] 128 54.0 [8.92] Week 44, n Mean [SD] 131 45.5 [12.70] 128 50.4 [13.48] 127 51.4 [12.63] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.7 [11.62] -3.3** [12.26] -3.0*** [11.06] Emotional functions Baseline, n Mean [SD] 131 60.4 [13.39] 129 61.1 [14.52] 127 62.8 [12.44] Week 44, n Mean [SD] 131 53.8 [16.26] 128 58.6 [17.05] 127 59.9 [15.99] Change from baseline Week 44, n 131 128 127 Mean [SD] -6.6 [15.76] -2.6** [17.46] -2.9** [13.42] Systemic symptoms Baseline, n Mean [SD] 130 23.1 [5.79] 129 23.2 [6.04] 128 23.9 [5.55] Week 44, n Mean [SD] 130 18.9 [7.78] 128 20.9 [7.41] 128 21.9 [7.14] Change from baseline Week 44, n 130 128 128 Mean [SD] -4.2 [7.42] -2.3* [7.77] -2.0** [6.19] Social functions Baseline, n Mean [SD] 131 27.8 [6.31] 129 27.9 [7.18] 127 28.8 [6.25] Week 44, n Mean [SD] 131 24.1 [8.98] 128 27.1 [8.20] 127 27.0 [7.80] Change from baseline Week 44, n 131 128 127 Mean [SD] -3.7 [7.67] -0.8*** [8.49] -1.8* [7.38] SF-36b,c 122 121 121 Physical functioning Baseline, n Mean [SD] 122 49.8 [7.70] 121 50.4 [8.51] 121 51.0 [7.33] Week 44, n Mean [SD] 122 46.7 [9.35] 121 48.5 [9.67] 121 50.6 [7.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.2 [8.42] -1.9 [7.94] -0.4** [5.63] Role-physical Baseline, n Mean [SD] 122 45.6 [9.75] 121 46.3 [9.93] 121 47.6 [9.37] Week 44, n Mean [SD] 122 40.8 [12.01] 121 43.4 [11.89] 121 46.0 [10.94] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.8 [11.87] -2.9 [12.73] -1.6** [8.79] Bodily pain Baseline, n Mean [SD] 122 47.1 [8.04] 121 48.8 [8.17] 121 48.2 [8.67] Week 44, n Mean [SD] 122 42.1 [10.65] 120 45.1 [11.34] 121 46.5 [10.97] Change from baseline Week 44, n 122 120 121 Mean [SD] -5.0 [10.61] -3.8 [11.73] -1.7** [8.87] General health Baseline, n Mean [SD] 122 39.5 [10.37] 121 40.0 [10.54] 121 40.7 [10.06] Week 44, n Mean [SD] 122 37.2 [10.94] 121 39.9 [11.31] 121 40.1 [11.03] Change from baseline Week 44, n 122 121 121 Mean [SD] -2.3 [10.18] -0.1* [10.25] -0.6 [8.78] Vitality Baseline, n Mean [SD]Week 44, n Mean [SD]Change from baseline Week 44, nMean [SD] 122 46.4 [10.27]122 41.4 [12.25]122-5.0 [11.77] 121 47.2 [10.82]120 44.8 [12.83]120-2.4* [12.42] 121 48.6 [10.94]121 45.6 [12.45]121-2.9* [10.38] Social functioning Baseline, n Mean [SD] 122 45.7 [8.89] 121 46.4 [10.17] 121 46.5 [9.54] Week 44, n Mean [SD] 122 41.5 [11.79] 121 44.1 [11.76] 121 45.3 [10.96] Change from baseline Week 44, n 122 121 121 Mean [SD] -4.2 [12.23] -2.3 [13.41] -1.2* [10.06] Role-emotional Baseline, n Mean [SD] 122 45.5 [11.95] 121 46.4 [10.90] 121 47.9 [9.64] Week 44, n Mean [SD] 122 42.2 [13.46] 121 44.6 [12.80] 121 46.5 [11.69] Change from baseline Week 44, n 122 121 121 Mean [SD] -3.3 [11.59] -1.8 [14.04] -1.4 [9.29] Mental health Baseline, n Mean [SD] 122 46.9 [10.68] 121 47.7 [10.11] 121 48.1 [10.30] Week 44, n Mean [SD] 122 42.0 [10.98] 120 45.6 [11.57] 121 47.0 [10.81] Change from baseline Week 44, n 122 120 121 Mean [SD] -4.9 [10.52] -2.3** [11.93] -1.1*** [9.85] IBDQ, Inflammatory Bowel Disease Questionnaire; IV, intravenous; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous; SD, standard deviation; SF-36, 36-Item Short Form Health Survey. aPatients who were in clinical response to ustekinumab IV induction dosing and were randomised to placebo SC on entry into this maintenance study. bPatients who had a prohibited Crohn’s disease-related surgery, had a loss of response, had prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be worsened Crohn’s disease before the designated analysis timepoint had their induction baseline value carried forward. cPatients who had insufficient data at the designated analysis timepoint had their last value carried forward. *p <0.050; **p <0.010; ***p <0.001. View Large 4. Discussion At study entry, participants in the UNITI trials had active CD with IBDQ and SF-36 scores consistent with moderate to severe impairment of HRQOL.10 Following treatment with IV ustekinumab 6 mg/kg or 130 mg, HRQOL scores improved considerably relative to placebo. At Week 8, greater proportions of patients receiving either ustekinumab 6 mg/kg or 130 mg demonstrated clinically important improvement in total IBDQ scores compared with placebo, with a greater effect evident in those who received the regulatory approved 6 mg/kg dose. Consistent with these observations, greater proportions of patients receiving ustekinumab 6 mg/kg and 130 mg demonstrated clinically significant improvement compared with placebo in both the PCS and MCS scores. Likewise, greater proportions of patients in the ustekinumab 6 mg/kg group achieved normal IBDQ, PCS, and MCS scores. It is noteworthy that HRQOL normalisation was more pronounced among ustekinumab-treated patients with an inadequate response or intolerance to conventional CD therapy [UNITI-2 population] than to TNF antagonists [UNITI-1 population]. This phenomenon, which was also observed in a recent analysis of patients treated with vedolizumab, is likely due to the greater prevalence of structural bowel damage in UNITI-1 participants who had higher disease activity and longer disease duration than those evaluated in UNITI-2. At the baseline visit of IM-UNITI, the mean baseline IBDQ scores approached the criterion for remission [≥170 points] and both PCS and MCS scores approximated the general US population mean norms of 50. At Week 44 in IM-UNITI, a dose-response relationship was observed with patient-reported outcomes, as was previously reported for improvements in signs and symptoms.5 This dose-response relationship favoured patients receiving q8w maintenance dosing compared with q12w dosing. Mean reductions in IBDQ scores from baseline at entry to IM-UNITI [i.e. Week 8] for the ustekinumab q12w and q8w dose groups were both significantly less compared with those assigned to placebo. This was also observed with SF-36 scores, where ustekinumab q8w was more likely to maintain improvement from induction therapy than ustekinumab q12w as measured by both the MCS and the PCS scores. This dose-response between q8w and q12w dosing at Week 44 was more apparent in parameters evaluating the more stringent endpoints of patients achieving clinically-important improvement in IBDQ, PCS, or MCS, or normalisation of IBDQ, PCS, or MCS scores. These results are consistent with the Week 44 primary endpoint [clinical remission] and major secondary endpoints [clinical response, remission in remitters, corticosteroid-free remission, and remission in TNF-naïve patients] where the ustekinumab q8w group was numerically greater than the q12w group for all endpoints.5 Collectively, these findings support the choice of the q8w dose regimen as being optimal for maintaining improved quality of life in patients who responded to induction therapy with ustekinumab. Previous studies with TNF antagonists, including infliximab, natalizumab, adalimumab, and vedolizumab, have shown that maintenance treatment with these therapies results in improved HRQOL in patients as assessed by multiple patient-reported outcome instruments.12–15 In conclusion, ustekinumab improved general health status and inflammatory bowel disease-specific HRQOL after a single intravenous infusion in patients with moderately to severely active CD, particularly ustekinumab 6 mg/kg, and improvements were better maintained with subcutaneous ustekinumab 90 mg q8w or q12w as compared with placebo. These results mirror the efficacy in clinical outcomes and inflammatory biomarkers reported previously.5 Funding This work was supported by Janssen Research & Development, LLC. Conflict of Interest BES has received honoraria for speaking in a CME conference from American Academy of CME, Inc., Catrille & Associates, Ltd, Creative Educational Concepts, Inc., Curatio CME Institute, Focus Medical Communications, LLC, Med-IQ, LLC, Rockpoint, Inc., IMEDEX, Scripps, Strategic Consultants International, and Vindico Medical Education; received consultant fees from Akros Pharma, Arena Pharmaceuticals, Cowen Services Company, LLC, Forest Research Institute, Inc., Forward Pharma, Immune Pharmaceuticals, Inc., MedImmune, Salix Pharmaceuticals, Inc., Strategic Consultants International, Synergy Pharmaceuticals, Theravance Biopharma R&D, Inc., TiGenix, UCB, and Vedanta Biosciences; received consulting fees for services on an advisory board for AbbVie, Amgen, AstraZeneca LP, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Luitpold Pharmaceuticals, Inc., Pfizer, Prometheus Laboratories, Receptos, Takeda, TopiVert Pharma; and received research grants from AbbVie, Amgen, Celgene, Janssen, Pfizer, Prometheus Laboratories, and Takeda. ST reports receiving consulting fees from Janssen Research & Development, LLC. WJS reports grants, personal fees, and non-financial support from AbbVie; grants and personal fees from Prometheus Laboratories, AbbVie, Boehringer Ingelheim, Takeda, Atlantic Pharmaceuticals, Janssen Research & Development, LLC, Bristol-Myers Squibb, Genentech, and Nutrition Science Partners; personal fees from Kyowa Hakko Kirin, Millennium Pharmaceuticals, Celgene Cellular Therapeutics, Santarus, Salix Pharmaceuticals, Catabasis Pharmaceuticals, Vertex Pharmaceuticals, Warner Chilcott, Gilead Sciences, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Sigmoid Biotechnologies, Tillotts Pharma, Am Pharma BV, Dr August Wolff, Avaxia Biologics, Zyngenia, Ironwood Pharmaceuticals, Index Pharmaceuticals, Nestle, Lexicon Pharmaceuticals, UCB Pharma, Orexigen, Luitpold Pharmaceuticals, Baxter Healthcare, Ferring Research Institute, Amgen, Novo Nordisk, Mesoblast, Inc., Shire, Ardelyx Inc., Actavis, Seattle Genetics, MedImmune [AstraZeneca], Actogenix NV, Lipid Therapeutics GmbH, Eisai, Qu Biologics, Toray Industries, Inc., Teva Pharmaceuticals, Eli Lilly, Chiasma, TiGenix, Adherion Therapeutics, Immune Pharmaceuticals, Celgene, Arena Pharmaceuticals, Ambrx, Inc., Akros Pharma, Vascular Biogenics, Theradiag, Forward Pharma, Regeneron, Galapagos, Seres Health, Ritter Pharmaceuticals, Theravance, Palatin, Biogen, and Western University [owner of Robarts Clinical Trials]. BGF has received consulting fees from Abbott/AbbVie, Ablynx, Actogenix, Akebia Therapeutics, Akros, Albireo Pharma, Allergan, Amgen, Applied Molecular Transport, Inc., Astra Zeneca, Atlantic Pharma, Avaxia Biologics, Inc., Avir Pharma, Baxter Healthcare Corp., Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, Galapagos, GiCare Pharma, Gilead, Given Imaging, Inc., GSK, Inception IBD, Inc., Ironwood Pharma, Janssen Research & Development, LLC, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nektar, Nestles, Nextbiotix, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Receptos, Roche/Genentech, Salix Pharma, Serano, Shire, Sigmoid Pharma, Synergy Pharma, Inc., Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, Vivelix Pharma, VHsquared Ltd, Warner-Chilcott, Wyeth, Zealand, Zyngenia; grant/research support from AbbVie, Inc., Amgen, Inc., AstraZeneca/MedImmune Ltd, Atlantic Pharmaceuticals Ltd, Boehringer-Ingelheim, Celgene Corporation, Celltech, Genentech ,Inc.,/Hoffmann-La Roche Ltd, Gilead Sciences, Inc., GlaxoSmithKline [GSK], Janssen Research & Development LLC, Pfizer, Inc., Receptos, Inc./Celgene International, Sanofi, Santarus, Inc., Takeda Development Center Americas, Inc., Tillotts Pharma AG, UCB; served as a Scientific Advisory Board member for Abbott/AbbVie, Allergan, Amgen, Astra Zeneca, Atlantic Pharma, Avaxia Biologics, Inc., Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Inc., Elan/Biogen, Ferring, Galapagos, Genentech/Roche, Janssen Research & Development, LLC, Merck, Nestles, Novartis, Novo Nordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Takeda, Teva, TiGenix, Tillotts Pharma AG, UCB Pharma; has been on the speakers bureau for Abbott/AbbVie, Janssen Research & Development, LLC, Lilly, Takeda, Tillotts, and UCB Pharma; and is a member of the Board of Directors for Robarts Clinical Trials, Inc., Western University, London, ON. CH is an employee of Janssen Biotech, Inc., CG, YL, DJ, L-LG, and PS are employees of Janssen Research & Development, LLC. Author Contributions The study concept and design were developed by BES, ST, WJS, and BGF in collaboration with the sponsor, Janssen Research & Development, LLC, and interpretation of data. BES, ST, WJS, and BGF were involved in the recruitment of study patients. All authors were involved in the analysis and/or interpretation of the data, and were involved in drafting the manuscript and critically reviewing it for important intellectual content. All authors had full access to the data in the study and had final responsibility for the decision to submit for publication. Conference presentations: these data were presented in part at the Annual Meeting of Digestive Diseases Week 2016 [San Diego, CA]. Acknowledgments Editorial and writing support was provided by Kirsten Schuck Gross, BS, and James P Barrett, BS, employees of Janssen Scientific Affairs, LLC. Statistical support was provided by Tianshu Ma, PhD, an employee of PRA Health Sciences funded by Janssen Scientific Affairs, LLC. References 1. Ware JE Jr , Sherbourne CD . The MOS 36-item short-form health survey [SF-36]. I. Conceptual framework and item selection . Med Care 1992 ; 30 : 473 – 83 . Google Scholar CrossRef Search ADS PubMed 2. Irvine EJ , Feagan B , Rochon J et al. Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Canadian Crohn’s Relapse Prevention Trial Study Group . Gastroenterology 1994 ; 106 : 287 – 96 . Google Scholar CrossRef Search ADS PubMed 3. Sands BE , Han C , Gasink C et al. Ustekinumab improves general health status and disease-specific health related quality of life of patients with moderate to severe Crohn’s disease: results from the UNITI and IMUNITI phase 3 clinical trials . Gastroenterology 2016 ; 150 : S1004 [abstract]. Google Scholar CrossRef Search ADS 4. Bernklev T , Jahnsen J , Lygren I , Henriksen M , Vatn M , Moum B . Health-related quality of life in patients with inflammatory bowel disease measured with the short form-36: psychometric assessments and a comparison with general population norms . Inflamm Bowel Dis 2005 ; 11 : 909 – 18 . Google Scholar CrossRef Search ADS PubMed 5. Feagan BG , Sandborn WJ , Gasink C et al. ; UNITI–IM-UNITI Study Group . Ustekinumab as induction and maintenance therapy for Crohn’s disease . N Engl J Med 2016 ; 375 : 1946 – 60 . Google Scholar CrossRef Search ADS PubMed 6. Pallis AG , Vlachonikolis IG , Mouzas IA . Assessing health-related quality of life in patients with inflammatory bowel disease, in Crete, Greece . BMC Gastroenterol 2002 ; 2 : 1 . Google Scholar CrossRef Search ADS PubMed 7. Irvine EJ . Development and subsequent refinement of the inflammatory bowel disease questionnaire: a quality-of-life instrument for adult patients with inflammatory bowel disease . J Pediatr Gastroenterol Nutr 1999 ; 28 : S23 – 7 . Google Scholar CrossRef Search ADS PubMed 8. Kosinski M , Zhao SZ , Dedhiya S , Osterhaus JT , Ware JE Jr . Determining minimally important changes in generic and disease-specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis . Arthritis Rheum 2000 ; 43 : 1478 – 87 . Google Scholar CrossRef Search ADS PubMed 9. Samsa G , Edelman D , Rothman ML , Williams GR , Lipscomb J , Matchar D . Determining clinically important differences in health status measures: a general approach with illustration to the Health Utilities Index Mark II . Pharmacoeconomics 1999 ; 15 : 141 – 55 . Google Scholar CrossRef Search ADS PubMed 10. Hlavaty T , Persoons P , Vermeire S et al. Evaluation of short-term responsiveness and cutoff values of inflammatory bowel disease questionnaire in Crohn’s disease . Inflamm Bowel Dis 2006 ; 12 : 199 – 204 . Google Scholar CrossRef Search ADS PubMed 11. Ware JE , Kosinski M , Keller SD. SF-36 Physical and Mental Health Summary Scales: A User’s Manual . Boston, MA : Health Institute ; 1994 . 12. Feagan BG , Yan S , Bala M , Bao W , Lichtenstein GR . The effects of infliximab maintenance therapy on health-related quality of life . Am J Gastroenterol 2003 ; 98 : 2232 – 8 . Google Scholar CrossRef Search ADS PubMed 13. Feagan BG , Sandborn WJ , Hass S , Niecko T , White J . Health-related quality of life during natalizumab maintenance therapy for Crohn’s disease . Am J Gastroenterol 2007 ; 102 : 2737 – 46 . Google Scholar CrossRef Search ADS PubMed 14. Loftus EV , Feagan BG , Colombel JF et al. Effects of adalimumab maintenance therapy on health-related quality of life of patients with Crohn’s disease: patient-reported outcomes of the CHARM trial . Am J Gastroenterol 2008 ; 103 : 3132 – 41 . Google Scholar CrossRef Search ADS PubMed 15. Feagan BG , Patel H , Colombel JF et al. Effects of vedolizumab on health-related quality of life in patients with ulcerative colitis: results from the randomised GEMINI 1 trial . Aliment Pharmacol Ther 2017 ; 45 : 264 – 75 . Google Scholar CrossRef Search ADS PubMed Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

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Journal of Crohn's and ColitisOxford University Press

Published: Aug 1, 2018

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