To compare disease burden and biologic use among psoriatic arthritis (PsA) or rheumatoid arthritis (RA) patients recruited to the Corrona registry. Retrospective study of patients with PsA or RA enrolled in Corrona between January 2002 and March 2013 and grouped in 2-year intervals. Clinical outcomes and biologic use were assessed. Biologic use increased over time in both cohorts, with 62 and 52% of patients with PsA and RA, respectively, receiving biologics by 2012–2013. However, 25 and 35% of patients with PsA and RA, respectively, continued to experience moderate/high disease activity. Overall, the progressive increase in biologic use accompanied progressive decreases in Clinical Disease Activity Index (from 14.2 to 10.4 for RA, and 12.4 to 8.1 for PsA) and mean Health Assessment Questionnaire score (from 0.36 to 0.34, and 0.3 to 0.24). Mean patient pain, the proportion of patients reporting morning stiffness, and the mean duration of morning stiffness remained similar for both cohorts. PsA and RA treated in the rheumatology setting had a comparable impact on patient quality of life and functional ability. Disease burden improved with increased biologic utilization in both groups; however, moderate/severe disease remains in a significant propor- tion of PsA and RA patients. . . . Keywords Biologics Disease burden Psoriatic arthritis Rheumatoid arthritis Introduction opportunity to diagnose and treat . Patients who develop joint manifestations are then typically referred to a rheumatol- Psoriatic arthritis (PsA) is a chronic, progressive, inflammato- ogist . One common treatment pathway is for patients to be ry arthritis, which affects 20–30% of patients with psoriasis offered initial therapy with one or more disease-modifying . Historically, PsA was considered to be a less severe form antirheumatic drugs (DMARDs), and if this initial treatment of inflammatory arthritis; however, it has since been demon- fails, a biologic drug is considered . strated that PsA can be associated with substantial joint dam- It is estimated that PsA-related joint erosions and destruc- age and disability . tions are similar to those of rheumatoid arthritis (RA) , Cutaneous lesions often precede the appearance of joint and yet, although the clinical burden of RA is well manifestations in PsA, so dermatologists often have the first established [5, 6], the clinical burden associated with PsA is not as adequately quantified . However, evidence sug- gests that the clinical features of PsA can culminate in re- duced physical and psychosocial health-related quality of life and an increased economic burden, with the latter * Arthur Kavanaugh resulting from direct medical costs and indirect costs due firstname.lastname@example.org to disability and lost productivity [7–9]. In this large, real-world study, we directly compared the University of California, San Diego, 9500 Gilman Drive, MC 0943, disease burden and use of biologic drugs between 2002 and La Jolla, CA 92093-0943, USA 2013 in patients with PsA or RA who had been referred to the AbbVie Inc., North Chicago, IL, USA rheumatology setting and enrolled in the Consortium of Corrona, LLC, Southborough, MA, USA Rheumatology Researchers of North America (Corrona) reg- Albany Medical College, Albany, NY, USA istry. The objective of this analysis was to discover whether New York University School of Medicine, New York, NY, USA the disease burden of PsA was different from that of RA, Clin Rheumatol whether this difference had changed over time, and whether private), comorbidities, current biologic use, and patient loca- biologic treatment patterns had altered in the wake of in- tion (by region). creases in published efficacy and safety data. Results Patients and methods Demographics and disease characteristics Study design and population Patient demographics and disease characteristics are presented This was a retrospective observational cohort study of patients in Table 1. Compared with RA patients, patients with PsA with PsA or RA enrolled in the Corrona registry between were, on average, younger and had an earlier disease onset. January 2002 and March 2013. The ongoing Corrona registry A greater proportion of PsA patients had a college/university is an independent, prospective observational cohort of patients education and/or had full-time employment. Although pa- with RA or PsA, recruited from 171 private and academic tients with RA were predominantly female, the PsA cohort practice sites across 40 states in the USA. As of April 2017, had an equal proportion of males and females. 676 rheumatologists and 45,722 patients had participated. Corrona registry patients aged > 18 years with a PsA or RA Disease activity, disability, and biologics use diagnosis and an eligible (last) visit between January 1, 2002 to March 31, 2013 were included in the study. PsA patients Over the study period, the use of biologics increased in both with axial symptoms were excluded from the analysis. Patient the PsA and RA cohorts, although over time, PsA patients visits during the study period were divided into 2-year inter- were > 30% more likely to receive a biologic than their RA vals and the last visit (enrollment or follow-up visit) for each counterparts (OR range from 1.03 to 1.42). By 2012–2013, patient within the 2-year interval was evaluated. 62% of patients with PsA were receiving a biologic compared with 52% of RA patients (Fig. 1a). The progressive increase in Outcomes of interest biologic use was accompanied by a similar progressive de- crease in overall disease activity over time. The mean CDAI Disease activity was measured by Clinical Disease Activity decreased from 12.4 to 8.1 in the PsA cohort, and from 14.2 to Index (CDAI), physical function was measured using modi- 10.4 in the RA cohort; while disease activity in the patients fied Health Assessment Questionnaire (mHAQ), current bio- with PsA remained slightly lower than that of their RA coun- logic use (abatacept, adalimumab, anakinra, certolizumab, terparts (ORs < 1.0 across all time points) (Fig. 1b). Despite etanercept, golimumab, infliximab, tocilizumab, rituximab), these improvements, 25 and 35% of patients with PsA and and individual disease symptoms such as pain (measured RA, respectively, continued to experience moderate or high using a visual analog scale (0–100)) and morning stiffness disease activity (CDAI > 10) in the last 2-year interval (2012– (% yes, and duration [< 1 or > 1 h]) were assessed and com- 2013) analyzed (Fig. 1c). pared between RA and PsA cohorts. The progressive increase in biologic use and decrease in disease activity was accompanied by a similar progressive Statistical analysis decrease in physical function, with the mean mHAQ in PsA patients being slightly lower than that of the RA patients over Descriptive statistics on patient characteristics were evaluated: time (Fig. 2a). Overall, the mean mHAQ decreased from 0.30 means, standard deviations (quantitative variables), and per- to 0.24 in the PsA cohort, and 0.36 to 0.34 in the RA cohort. centages (categorical variables) were presented. Standardized However, other patient-reported outcomes such as mean pa- differences were calculated to compare the distribution of pa- tient pain (Fig. 2b), the proportion of patients reporting morn- tient characteristics, both quantitative and categorical, in pa- ing stiffness (Fig. 2c), and the mean duration of morning stiff- tients with RA and PsA across each 2-year time interval. ness (data not shown) remained similar between RA and PsA Logistic regression models were used to estimate adjusted patients for the duration of the study. odds ratio (OR, 95% confidence interval) to evaluate the like- lihood of a patient having moderate/high disease activity (based on CDAI) and the use of biologics in patients with Discussion PsA compared to that with patients with RA, adjusting for covariates within each time period. Covariates used in the The disease burden associated with RA is well established [5, model included age (years), gender (male/female), duration 6]; the PsA-related burden less so. Our data show that PsA and of disease (years), age at disease onset, education (% with RA patients, when treated in the rheumatologist’s office, show primary, high school, or college/university), insurance (% comparable improvements in patient quality of life and Clin Rheumatol Table 1 Demographics and disease characteristics of patients with PsA and RA across the study period 2002–2003 2004–2005 2006–2007 2008–2009 2010–2011 2012–2013 RA PsA RA PsA RA PsA RA PsA RA PsA RA PsA n = 4763 n = 457 n = 9494 n = 1055 n = 13,206 n = 1699 n = 16,645 n =2163 n = 20,273 n = 2522 n = 20,982 n = 2552 Age, years 59.0 (13.4) 52.9 (13.1) 59.8 (13.4) 52.9 (12.6) 60.0 (13.6) 53.4 (12.7) 60.0 (13.7) 54.0 (12.8) 60.4 (13.4) 54.3 (12.9) 61.1 (13.1) 54.7 (12.8) Female (%) 74.5 50.7 74.7 50.3 76.1 51.6 76.50 51.50 76.70 52.20 76.70 53.50 BMI 28.6 (6.7) 30.7 (6.9) 28.7 (6.8) 30.9 (7.1) 29.2 (7.5) 31.4 (7.8) 29.0 (6.9) 30.9 (7.1) 29.2 (7.0) 31.1 (7.1) 29.4 (7.0) 31.2 (6.9) White (%) 89.1 92.8 89.8 95.4 87.6 93.6 87.6 94.3 87.4 93.6 87.9 92.3 College/university (%) 47.7 59.3 48.2 60.1 51.9 63.9 54.9 66.6 56.2 69.0 58.5 70.4 Full-time employment (%) 32.6 56.1 31.5 52.0 33.4 56.5 35.2 55.0 35.4 54.8 34.7 55.1 Age at disease onset 48.3 (14.6) 43.7 (14.1) 48.6 (14.7) 43.3 (14.0) 48.6 (14.9) 43.7 (14.0) 48.5 (14.8) 43.8 (13.8) 48.7 (14.5) 43.9 (13.8) 48.9 (14.4) 44.3 (13.7) Duration of disease (years) 10.7 (9.7) 9.4 (8.9) 11.3 (9.9) 9.7 (9.2) 11.5 (10.2) 9.8 (8.9) 11.7 (10.1) 10.2 (9.0) 11.8 (10.1) 10.4 (9.2) 12.3 (10.3) 10.4 (9.2) Swollen joint count (0–28) 4.3 (5.2) 3.2 (4.4) 4.3 (5.8) 2.6 (4.4) 3.4 (5.2) 2.0 (4.0) 2.8 (4.4) 1.6 (3.4) 2.7 (4.3) 1.7 (3.7) 2.5 (4.1) 1.6 (3.4) Tender joint count (0–28) 4.1 (5.7) 3.5 (5.0) 3.4 (5.4) 2.7 (4.4) 3.0 (5.3) 2.3 (4.4) 2.8 (5.0) 2.2 (4.4) 3.1 (5.3) 2.5 (5.0) 3.2 (5.4) 2.5 (4.8) Patient global assessment (VAS 0–100) 32.3 (25.5) 31.9 (25.2) 27.9 (25.3) 25.8 (24.2) 29.1 (25.6) 27.0 (24.4) 29.3 (26.3) 26.0 (24.1) 29.1 (26.5) 26.8 (25.7) 29.8 (26.5) 26.5 (25.2) Physician global assessment (VAS 0–100) 26.5 (21.1) 25.5 (20.6) 21.0 (19.6) 18.7 (18.3) 17.7 (18.1) 15.1 (15.5) 17.0 (18.2) 14.3 (15.9) 17.6 (18.9) 15.0 (16.8) 17.6 (18.8) 14.3 (16.5) Erosive disease, yes (%) 57.2 52.4 53.2 42.7 53.6 40.9 52.7 39.6 49.8 38.1 44.6 35.1 Data are mean and SD unless otherwise specified BMI, body mass index; PsA, psoriatic arthritis; RA, rheumatoid arthritis; VAS, visual analog scale Clin Rheumatol Fig. 1 Current biologic use (a), mean disease activity (b), and disease biologic use (except for a) and region of country. CI, confidence interval; activity by CDAI categories (c) in patients with PsA and RA across the CDAI, clinical disease activity index; PsA, psoriatic arthritis; RA, study period. Covariates used in the models were age, gender, duration of rheumatoid arthritis disease, age of disease onset, education, insurance, comorbidities, current functional ability. Although joint burden, as measured by Some current treatment recommendations for PsA suggest mean CDAI, was slightly lower in PsA patients than that in treatment with anti-inflammatory drugs and a combination of RA patients, rheumatologists utilized biologic agents more one or more DMARDs before administering biologic drugs frequently among the PsA patients. . However, the efficacy of DMARDs has not been proven Our results show that over the study period, 2002 until across all of the diverse manifestations of the disease. 2013, there was an increase in the use of biologic drugs. Traditional DMARDs have been shown to be ineffective for Over this same time period, there was a progressive decrease the axial manifestations of ankylosing spondylitis, and there in disease burden for both RA and PsA. However, by the end are no data to suggest axial symptoms in PsA patients of the study, about a quarter of patients with PsA and one third would be effectively treated by such agents . For other of patients with RA continued to experience moderate/high manifestations, such as enthesitis and dactylitis, evidence disease activity. supporting the clinical efficacy of targeted biological therapies A delay of 1 year between symptom onset and diagnosis in PsA is much more robust than that for traditional therapies has been associated with poorer physical function in [13, 14]. established PsA , while clinical and radiographic damage Our study had some limitations. Corrona is an observation- have been shown to be more marked in patients presenting al registry and its data were restricted to information captured with > 2 years of disease duration before treatment is initiated routinely by US physicians in regular clinical practice (e.g., [11, 12]. Peripheral joint erosions and worse functional out- CDAI was evaluated as laboratory measures, a key compo- comes have also been demonstrated with a delay as short as nent of other composite indexes used in clinical trials that are 6 months from symptom onset to the first rheumatology visit not routinely collected). Additionally, as CDAI is based on a . Therefore, early diagnosis and effective treatment of PsA 28-joint count, additional disease impact on joints beyond may help prevent long-term joint damage and disability. those evaluated are not represented. Our registry data were Clin Rheumatol Fig. 2 Physical function (a), patient pain (b), and morning stiffness (c) in patients with PsA and RA across the study period. Covariates used in the models were age, gender, duration of disease, age of disease onset, education, insurance, comorbidities, current biologic use, and region of country. CI, confidence interval; mHAQ, modified Health Assessment Questionnaire; PsA, psoriatic arthritis; RA, rheumatoid arthritis; VAS, visual analog scale also restricted to assessing the impact of PsA on joints; so from RA patients in the Corrona registry with their corre- despite measurements being more widespread now, data on sponding Medicare data. As hypothesized above, the authors skin involvement and impact of extra-articular manifestations foundthattheCorronapatientsweremorelikelytotake were not investigated during the study period. Additionally, DMARDs and biologic agents, but that other than this differ- the data are from a rheumatology setting, so there may be ence, the demographics and comorbidity profiles of these reg- referral bias in that PsA patients who require biologics are istry patients were generalizable to the US Medicare popula- more likely to be referred here; there may well be a larger tion . percentage of untreated patients in community practices. As Our study assessment period ended in March 2013. Future with all registries, the characteristics of the enrolled patient research should focus on evolving trends in the treatment of population may not be entirely representative of the entire PsA since this time and should directly compare the safety and patient population. These hypotheses were partly assessed in efficacy of other RA/PsA medications in both the dermatolo- a linkage study by Curtis et al., which matched 30,000 records gy and rheumatology settings. Clin Rheumatol Conclusions References The overall disease burden of PsA remains slightly lower than 1. Reich K, Kruger K, Mossner R, Augustin M (2009) Epidemiology and clinical pattern of psoriatic arthritis in Germany: a prospective that of RA, but some joint-related symptoms (i.e., pain, morn- interdisciplinary epidemiological study of 1511 patients with ing stiffness) are comparable. The PsA disease burden report- plaque-type psoriasis. Br J Dermatol 160:1040–1047. https://doi. ed in the rheumatology setting has decreased during the past org/10.1111/j.1365-2133.2008.09023.x decade, and this appears to have coincided with an increased 2. Ogdie A, Weiss P (2015) The epidemiology of psoriatic arthritis. Rheum Dis Clin N Am 41:545–568. https://doi.org/10.1016/j.rdc. use of biologic treatments. However, there continues to be a 2015.07.001 substantial proportion of PsA patients with moderate/high dis- 3. Yamamoto T (2011) Psoriatic arthritis: from a dermatological per- ease activity. Therefore, earlier and more targeted treatment of spective. Eur J Dermatol 21:660–666. https://doi.org/10.1684/ejd. PsA joint symptoms may help to improve long-term 2011.1452 outcomes. 4. Coates LC, Helliwell PS (2017) Psoriatic arthritis: state of the art review. Clin Med (Lond) 17:65–70. https://doi.org/10.7861/ clinmedicine.17-1-65 Author contributions A. Kavanaugh, C. Karki, C. Etzel, and J. Griffith 5. Uhlig T, Moe RH, Kvien TK (2014) The burden of disease in contributed to the study concept, refinement of the study design, and rheumatoid arthritis. PharmacoEconomics 32:841–851. https:// statistical analysis. R. Singh, J. Kremer, and J. Greenberg contributed to doi.org/10.1007/s40273-014-0174-6 the refinement of the study design. All the authors contributed to the review of data output, interpretation of results, and critical revision of 6. Cross M, Smith E, Hoy D, Carmona L, Wolfe F, Vos T, Williams B, manuscript. Gabriel S, Lassere M, Johns N, Buchbinder R, Woolf A, March L (2014) The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 73:1316– Funding This study is sponsored by Corrona, LLC. Corrona has been 1322. https://doi.org/10.1136/annrheumdis-2013-204627 supported through contracted subscriptions in the last 2 years by AbbVie, 7. Lee S, Mendelsohn A, Sarnes E (2010) The burden of psoriatic Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Crescendo, Eli arthritis: a literature review from a global health systems perspec- Lilly and Company, Genentech, Gilead, GSK, Horizon Pharma USA, tive. P T 35:680–689 Janssen, Momenta Pharmaceuticals, Novartis, Pfizer Inc., Roche, Merck, UCB, and Valeant. The design, study conduct, and financial sup- 8. Borman P, Toy GG, Babaoglu S, Bodur H, Ciliz D, Alli N port for the study were provided by AbbVie. 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Sponsor approval CS, McHugh N (2013) Smoking and delay to diagnosis are associ- and continuing review was obtained through a central IRB (New ated with poorer functional outcome in psoriatic arthritis. Ann England Independent Review board, NEIRB No. 02-021). For aca- Rheum Dis 72:1358–1361. https://doi.org/10.1136/annrheumdis- demic investigative sites that did not receive a waiver to use the 2012-202608 central IRB, full board approval was obtained from the respective 11. Gladman DD, Thavaneswaran A, Chandran V, Cook RJ (2011) Do governing IRBs and documentation of approval was submitted to patients with psoriatic arthritis who present early fare better than the Sponsor prior to initiating any study procedures. those presenting later in the disease? Ann Rheum Dis 70:2152– 2154. https://doi.org/10.1136/ard.2011.150938 Informed consent All registry subjects were required to provide written 12. Haroon M, Gallagher P, FitzGerald O (2015) Diagnostic delay of informed consent and authorization prior to participating. more than 6 months contributes to poor radiographic and functional outcome in psoriatic arthritis. Ann Rheum Dis 74:1045–1050. Disclosures Dr. Kavanaugh has served as a consultant to AbbVie and https://doi.org/10.1136/annrheumdis-2013-204858 has conducted clinical research sponsored by AbbVie. Chitra Karki and 13. Boyd T, Kavanaugh A (2016) Novel approaches to biological ther- Carol Etzel are Corrona employees. Dr. Kremer is a Corrona employee apy for psoriatic arthritis. Expert Opin Biol Ther 16:173–186. and has provided consulting services and received research grant support https://doi.org/10.1517/14712598.2016.1118045 from AbbVie. Dr. Greenberg is an employee and shareholder of Corrona. 14. Mease P (2006) Management of psoriatic arthritis: the therapeutic Rakesh Singh and Jenny Griffith are AbbVie employees and own com- interface between rheumatology and dermatology. Curr Rheumatol pany stock. Editorial assistance was provided by Madhuri Vemuri and Rep 8:348–354 Steve Dawber of Fishawack Communications Ltd. AbbVie provided 15. Curtis JR, Chen L, Bharat A, Delzell E, Greenberg JD, Harrold L, funding to Fishawack for this work. Kremer J, Setoguchi S, Solomon DH, Xie F, Yun H (2014) Linkage of a de-identified United States rheumatoid arthritis registry with Open Access This article is distributed under the terms of the Creative administrative data to facilitate comparative effectiveness research. Commons Attribution 4.0 International License (http:// Arthritis Care Res (Hoboken) 66:1790–1798. https://doi.org/10. creativecommons.org/licenses/by/4.0/), which permits unrestricted use, 1002/acr.22377 distribution, and reproduction in any medium, provided you give appro- priate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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Published: Jun 4, 2018