Apremilast for the treatment of active psoriatic arthritis: a single-centre real-life experience

Apremilast for the treatment of active psoriatic arthritis: a single-centre real-life experience Rheumatology key message Real-life experience of apremilast in PsA suggests enhanced efficacy in early disease. Sir, Apremilast (Otezla; Celgene, Summit, NJ, USA) is a small-molecule phosphodiesterase-4 inhibitor that offers a novel oral therapeutic option for patients with psoriasis and PsA. Recent randomized controlled trials (RCTs) show that apremilast is effective in both psoriasis and PsA [1–6], however, there is still a paucity of real-life data in unselected patients. We performed, at our tertiary centre, a retrospective analysis of the effectiveness and tolerability of apremilast at a standard dose of 30 mg twice a day in subjects with PsA treated in a dedicated outpatient clinic following a zero cost scheme prior to National Institute for Health and Care Excellence approval in the UK. All subjects fulfilled classification criteria for PsA [7] and had active disease according to the treating clinician. In addition, all subjects had previously been exposed to adequate trials of DMARDs. Ethical approval was not required, as this report was an audit of standard practice and service evaluation. As part of our local clinic algorithms, subjects were assessed at baseline and every 6 months (s.d. 3). Clinical assessments at each visit included tender (0–78) and swollen (0–76) joint count and CRP levels. When patient and physician global assessments on a 5-point Likert scale were available on clinical notes review, PsA response criteria were also calculated [8]. Subjects were classified as responders and non-responders based on the overall physician judgement of clinical status (yes/no), specifically, the absence of peripheral arthritis, enthesitis and dactylitis on clinical examination; or improvement of clinical signs at physical examination and concurrent patient’s reported improvement of symptoms as per PsA response criteria. Response was defined based on the last available follow-up assessment as compared with the baseline evaluation. Binomial variables were expressed as number and percentage and continuous variables as median (range) or mean (s.d.) as appropriate. Comparisons between baseline and follow-up measurements were performed using Wilcoxon matched pairs signed-rank test. Significant differences between responders and non-responders were defined as those at a level of P < 0.05 by unpaired t test or Fisher’s or χ2 test. Statistical analysis was carried out using GraphPad Prism version 7.0 (GraphPad Software, La Jolla, CA, USA). A total of 71 patients [n = 33 (46.5%) male] with a mean follow-up of 172.6 days (s.d. 105.5) were identified and included in this report. Clinical characteristics are summarized in Table 1. Of the 71 patients started on apremilast, 51 had at least a 6 months (s.d. 3) of follow-up assessment. Based on overall clinician judgement, 31 of 51 (60.8%) patients were classified as responders and 20 (39.2%) as non-responders. In patients in which joint count was recorded at the baseline and at the follow-up assessment (n = 22), there was a statistically significant improvement of tender (P = 0.004) and swollen (P = 0.003) joint counts. In patients with abnormal CRP levels at baseline, measurements slightly decreased at follow-up (P = 0.04). Of note, responders had a shorter disease duration compared with non-responders [5.23 (s.d. 4.46) vs 9.15 (6.8) years; P = 0.016] and had a lower exposure to previous biologic DMARDS (P = 0.0055) and conventional or synthetic DMARDS, although this latter difference did not reach statistical significance (P > 0.05). No other significant differences were found between the two groups. Table 1 Baseline clinical characteristics of 71 PsA patients treated with apremilast Male, n (%)  33 (46.5)  Age, mean (s.d.), years  51 (13.2)  PsA disease duration, mean (s.d.), years  7.7 (6.4)  Peripheral involvement (all polyarticular), n (%)  71 (100)  Axial involvement, n (%)  22 (31)  Psoriasis, n (%)  59 (83.1)  Nail involvement, n (%)  20 (44.4)  Entheseal/dactylitis involvement, n (%)  38 (60.3)  CRP baseline, median (range), mg/l  7.1 (5–115)  Tender joint count, median (range)  7 (0–40)  Swollen joint count, median (range)  3 (0–16)  Patient’s disease activity (1–5), median (range)  4 (1–5)  Physician’s disease activity (1–5), median (range)  3 (1–5)  Current cDMARDS, n (%)      MTX  18 (25)      SZ  1 (1.4)      HCQ  2 (2.8)      LEF  1 (1.4)      Combination (MTX + SZ, MTX + HCQ)  2 (2.8)  Current bDMARDS, n (%)      Certolizumab  2 (2.8)      Golimumab  2 (2.8)      Ustekinumab  2 (2.8)      Adalimumab  1 (1.4)      Etanercept  1 (1.4)      Secukinumab  1 (1.4)      Tocilizumab  1 (1.4)  Previous cDMARDS, n (%)  67 (94.4)  Previous bDMARDS, n (%)  40 (56.3)  Contraindication to bDMARDS, n (%)  10 (14.1)  Apremilast discontinuation, n (%)  28 (39.4)      Ineffective  11 (15.5)      Side effects  27 (38)          GI symptoms  19          General malaise  2          Headache  8          Depression, suicidal ideation  2, 1  Time to discontinuation, days        Mean (s.d.)  129.7 (77.7)      Median (range)  132 (21–313)  Time of follow-up, days        Mean (s.d.)  172.6 (105.5)      Median (range)  153 (21–519)  Male, n (%)  33 (46.5)  Age, mean (s.d.), years  51 (13.2)  PsA disease duration, mean (s.d.), years  7.7 (6.4)  Peripheral involvement (all polyarticular), n (%)  71 (100)  Axial involvement, n (%)  22 (31)  Psoriasis, n (%)  59 (83.1)  Nail involvement, n (%)  20 (44.4)  Entheseal/dactylitis involvement, n (%)  38 (60.3)  CRP baseline, median (range), mg/l  7.1 (5–115)  Tender joint count, median (range)  7 (0–40)  Swollen joint count, median (range)  3 (0–16)  Patient’s disease activity (1–5), median (range)  4 (1–5)  Physician’s disease activity (1–5), median (range)  3 (1–5)  Current cDMARDS, n (%)      MTX  18 (25)      SZ  1 (1.4)      HCQ  2 (2.8)      LEF  1 (1.4)      Combination (MTX + SZ, MTX + HCQ)  2 (2.8)  Current bDMARDS, n (%)      Certolizumab  2 (2.8)      Golimumab  2 (2.8)      Ustekinumab  2 (2.8)      Adalimumab  1 (1.4)      Etanercept  1 (1.4)      Secukinumab  1 (1.4)      Tocilizumab  1 (1.4)  Previous cDMARDS, n (%)  67 (94.4)  Previous bDMARDS, n (%)  40 (56.3)  Contraindication to bDMARDS, n (%)  10 (14.1)  Apremilast discontinuation, n (%)  28 (39.4)      Ineffective  11 (15.5)      Side effects  27 (38)          GI symptoms  19          General malaise  2          Headache  8          Depression, suicidal ideation  2, 1  Time to discontinuation, days        Mean (s.d.)  129.7 (77.7)      Median (range)  132 (21–313)  Time of follow-up, days        Mean (s.d.)  172.6 (105.5)      Median (range)  153 (21–519)  Percentage in parenthesis is calculated based on the number of patients with the specific feature among the total patients with the available data on clinical notes review. bDMARDS: biologic DMARDs; cDMARDS: conventional DMARDs. A total of 28 (39.4%) subjects required drug discontinuation after a mean period of 129.7 days (s.d. 77.7) due to a lack of efficacy and/or side effects. Overall, 27 (38%) patients developed one or more side effects (Table 1). The most common side effects were gastrointestinal (GI) symptoms (19/71), including nausea (9/71), vomiting (3/71), diarrhoea (13/71) and abdominal pain with loss of appetite (1/71). Two patients experienced depression (2.8%), of which one had associated suicidal ideation and concomitant headache and GI symptoms that required drug withdrawal in week 8. To our knowledge, this is the first real-life report of the use of apremilast in unselected PsA patients. Previously published RCTs have shown that apremilast is effective in patients with PsA and psoriasis, with an acceptable safety profile. In patients with PsA treated with apremilast 30 mg twice a day, the 20% improvement in ACR criteria response ranged between 32.1 and 41% at week 16 in three different phase 3 RCTs [4–6]. Despite using different response criteria, our data from an unselected tertiary centre population confirm these results. The main limitations of our report are the small numbers treated and the amount of missing data that reflects a real population observation, which is due in part to the use of paper-based assessments in our hospital. An important observation however, and despite the low numbers, is that clinical response appeared to be enhanced in the subset of patients with shorter disease duration, suggesting that apremilast may be better placed earlier on in the treatment algorithm for PsA, although this observation will need to be confirmed with larger numbers. In conclusion, our data provide real-life evidence of the short-term efficacy of apremilast in the treatment of active PsA and suggest that this may be enhanced in earlier disease stages. Apremilast represents a valuable additional oral synthetic molecule for the treatment of PsA. Larger observational cohort studies with health economic evaluations will help confirm the placing of apremilast in the treatment algorithm for PsA. Acknowledgements G.A. was supported by a grant from the Fondazione Italiana per la Ricerca sull’Artrite (FIRA ONLUS). The research was supported by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: H.M.O. has received grants and/or honoraria from AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. G.A. has received honoraria from Celgene, UCB, Pfizer, Italfamaco, Actelion and MSD. D.M.G. has undertaken research and/or educational programme activity with Pfizer, MSD, AbbVie, Bristol-Meyers Squibb, UCB, Novartis, Celgene and Johnson & Johnson. All other authors have declared no conflicts of interest. References 1 Papp K , Reich K, Leonardi CL et al.   Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM 1]). J Am Acad Dermatol  2015; 73: 37– 49. http://dx.doi.org/10.1016/j.jaad.2015.03.049 Google Scholar CrossRef Search ADS PubMed  2 Paul C , Cather J, Gooderham M et al.   Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe plaque psoriasis over 52 weeks: a phase III, randomized, controlled trial (ESTEEM 2). Br J Dermatol  2015; 173: 1387– 99. http://dx.doi.org/10.1111/bjd.14164 Google Scholar CrossRef Search ADS PubMed  3 Schett G , Wollenhaupt J, Papp K et al.   Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum  2012; 64: 3156– 67. http://dx.doi.org/10.1002/art.34627 Google Scholar CrossRef Search ADS PubMed  4 Kavanaugh A , Mease PJ, Gomez-Reino JJ et al.   Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis  2014; 73: 1020. http://dx.doi.org/10.1136/annrheumdis-2013-205056 Google Scholar CrossRef Search ADS PubMed  5 Cutolo M , Myerson GE, Fleischmann RM et al.   A phase III, randomized, con- trolled trial of apremilast in patients with psoriatic arthritis: results of the PALACE 2 trial. J Rheumatol  2016; 43: 1724– 34. http://dx.doi.org/10.3899/jrheum.151376 Google Scholar CrossRef Search ADS PubMed  6 Edwards CJ , Blanco FJ, Crowley J et al.   Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis  2016; 75: 1065– 73. http://dx.doi.org/10.1136/annrheumdis-2015-207963 Google Scholar CrossRef Search ADS PubMed  7 Taylor W , Gladman D, Helliwell P et al.   Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum  2006; 54: 2665– 73. http://dx.doi.org/10.1002/art.21972 Google Scholar CrossRef Search ADS PubMed  8 Mease PJ , Goffe BS, Metz J et al.   Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet  2000; 356: 385– 90. http://dx.doi.org/10.1016/S0140-6736(00)02530-7 Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Rheumatology Oxford University Press

Apremilast for the treatment of active psoriatic arthritis: a single-centre real-life experience

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© The Author(s) 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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Abstract

Rheumatology key message Real-life experience of apremilast in PsA suggests enhanced efficacy in early disease. Sir, Apremilast (Otezla; Celgene, Summit, NJ, USA) is a small-molecule phosphodiesterase-4 inhibitor that offers a novel oral therapeutic option for patients with psoriasis and PsA. Recent randomized controlled trials (RCTs) show that apremilast is effective in both psoriasis and PsA [1–6], however, there is still a paucity of real-life data in unselected patients. We performed, at our tertiary centre, a retrospective analysis of the effectiveness and tolerability of apremilast at a standard dose of 30 mg twice a day in subjects with PsA treated in a dedicated outpatient clinic following a zero cost scheme prior to National Institute for Health and Care Excellence approval in the UK. All subjects fulfilled classification criteria for PsA [7] and had active disease according to the treating clinician. In addition, all subjects had previously been exposed to adequate trials of DMARDs. Ethical approval was not required, as this report was an audit of standard practice and service evaluation. As part of our local clinic algorithms, subjects were assessed at baseline and every 6 months (s.d. 3). Clinical assessments at each visit included tender (0–78) and swollen (0–76) joint count and CRP levels. When patient and physician global assessments on a 5-point Likert scale were available on clinical notes review, PsA response criteria were also calculated [8]. Subjects were classified as responders and non-responders based on the overall physician judgement of clinical status (yes/no), specifically, the absence of peripheral arthritis, enthesitis and dactylitis on clinical examination; or improvement of clinical signs at physical examination and concurrent patient’s reported improvement of symptoms as per PsA response criteria. Response was defined based on the last available follow-up assessment as compared with the baseline evaluation. Binomial variables were expressed as number and percentage and continuous variables as median (range) or mean (s.d.) as appropriate. Comparisons between baseline and follow-up measurements were performed using Wilcoxon matched pairs signed-rank test. Significant differences between responders and non-responders were defined as those at a level of P < 0.05 by unpaired t test or Fisher’s or χ2 test. Statistical analysis was carried out using GraphPad Prism version 7.0 (GraphPad Software, La Jolla, CA, USA). A total of 71 patients [n = 33 (46.5%) male] with a mean follow-up of 172.6 days (s.d. 105.5) were identified and included in this report. Clinical characteristics are summarized in Table 1. Of the 71 patients started on apremilast, 51 had at least a 6 months (s.d. 3) of follow-up assessment. Based on overall clinician judgement, 31 of 51 (60.8%) patients were classified as responders and 20 (39.2%) as non-responders. In patients in which joint count was recorded at the baseline and at the follow-up assessment (n = 22), there was a statistically significant improvement of tender (P = 0.004) and swollen (P = 0.003) joint counts. In patients with abnormal CRP levels at baseline, measurements slightly decreased at follow-up (P = 0.04). Of note, responders had a shorter disease duration compared with non-responders [5.23 (s.d. 4.46) vs 9.15 (6.8) years; P = 0.016] and had a lower exposure to previous biologic DMARDS (P = 0.0055) and conventional or synthetic DMARDS, although this latter difference did not reach statistical significance (P > 0.05). No other significant differences were found between the two groups. Table 1 Baseline clinical characteristics of 71 PsA patients treated with apremilast Male, n (%)  33 (46.5)  Age, mean (s.d.), years  51 (13.2)  PsA disease duration, mean (s.d.), years  7.7 (6.4)  Peripheral involvement (all polyarticular), n (%)  71 (100)  Axial involvement, n (%)  22 (31)  Psoriasis, n (%)  59 (83.1)  Nail involvement, n (%)  20 (44.4)  Entheseal/dactylitis involvement, n (%)  38 (60.3)  CRP baseline, median (range), mg/l  7.1 (5–115)  Tender joint count, median (range)  7 (0–40)  Swollen joint count, median (range)  3 (0–16)  Patient’s disease activity (1–5), median (range)  4 (1–5)  Physician’s disease activity (1–5), median (range)  3 (1–5)  Current cDMARDS, n (%)      MTX  18 (25)      SZ  1 (1.4)      HCQ  2 (2.8)      LEF  1 (1.4)      Combination (MTX + SZ, MTX + HCQ)  2 (2.8)  Current bDMARDS, n (%)      Certolizumab  2 (2.8)      Golimumab  2 (2.8)      Ustekinumab  2 (2.8)      Adalimumab  1 (1.4)      Etanercept  1 (1.4)      Secukinumab  1 (1.4)      Tocilizumab  1 (1.4)  Previous cDMARDS, n (%)  67 (94.4)  Previous bDMARDS, n (%)  40 (56.3)  Contraindication to bDMARDS, n (%)  10 (14.1)  Apremilast discontinuation, n (%)  28 (39.4)      Ineffective  11 (15.5)      Side effects  27 (38)          GI symptoms  19          General malaise  2          Headache  8          Depression, suicidal ideation  2, 1  Time to discontinuation, days        Mean (s.d.)  129.7 (77.7)      Median (range)  132 (21–313)  Time of follow-up, days        Mean (s.d.)  172.6 (105.5)      Median (range)  153 (21–519)  Male, n (%)  33 (46.5)  Age, mean (s.d.), years  51 (13.2)  PsA disease duration, mean (s.d.), years  7.7 (6.4)  Peripheral involvement (all polyarticular), n (%)  71 (100)  Axial involvement, n (%)  22 (31)  Psoriasis, n (%)  59 (83.1)  Nail involvement, n (%)  20 (44.4)  Entheseal/dactylitis involvement, n (%)  38 (60.3)  CRP baseline, median (range), mg/l  7.1 (5–115)  Tender joint count, median (range)  7 (0–40)  Swollen joint count, median (range)  3 (0–16)  Patient’s disease activity (1–5), median (range)  4 (1–5)  Physician’s disease activity (1–5), median (range)  3 (1–5)  Current cDMARDS, n (%)      MTX  18 (25)      SZ  1 (1.4)      HCQ  2 (2.8)      LEF  1 (1.4)      Combination (MTX + SZ, MTX + HCQ)  2 (2.8)  Current bDMARDS, n (%)      Certolizumab  2 (2.8)      Golimumab  2 (2.8)      Ustekinumab  2 (2.8)      Adalimumab  1 (1.4)      Etanercept  1 (1.4)      Secukinumab  1 (1.4)      Tocilizumab  1 (1.4)  Previous cDMARDS, n (%)  67 (94.4)  Previous bDMARDS, n (%)  40 (56.3)  Contraindication to bDMARDS, n (%)  10 (14.1)  Apremilast discontinuation, n (%)  28 (39.4)      Ineffective  11 (15.5)      Side effects  27 (38)          GI symptoms  19          General malaise  2          Headache  8          Depression, suicidal ideation  2, 1  Time to discontinuation, days        Mean (s.d.)  129.7 (77.7)      Median (range)  132 (21–313)  Time of follow-up, days        Mean (s.d.)  172.6 (105.5)      Median (range)  153 (21–519)  Percentage in parenthesis is calculated based on the number of patients with the specific feature among the total patients with the available data on clinical notes review. bDMARDS: biologic DMARDs; cDMARDS: conventional DMARDs. A total of 28 (39.4%) subjects required drug discontinuation after a mean period of 129.7 days (s.d. 77.7) due to a lack of efficacy and/or side effects. Overall, 27 (38%) patients developed one or more side effects (Table 1). The most common side effects were gastrointestinal (GI) symptoms (19/71), including nausea (9/71), vomiting (3/71), diarrhoea (13/71) and abdominal pain with loss of appetite (1/71). Two patients experienced depression (2.8%), of which one had associated suicidal ideation and concomitant headache and GI symptoms that required drug withdrawal in week 8. To our knowledge, this is the first real-life report of the use of apremilast in unselected PsA patients. Previously published RCTs have shown that apremilast is effective in patients with PsA and psoriasis, with an acceptable safety profile. In patients with PsA treated with apremilast 30 mg twice a day, the 20% improvement in ACR criteria response ranged between 32.1 and 41% at week 16 in three different phase 3 RCTs [4–6]. Despite using different response criteria, our data from an unselected tertiary centre population confirm these results. The main limitations of our report are the small numbers treated and the amount of missing data that reflects a real population observation, which is due in part to the use of paper-based assessments in our hospital. An important observation however, and despite the low numbers, is that clinical response appeared to be enhanced in the subset of patients with shorter disease duration, suggesting that apremilast may be better placed earlier on in the treatment algorithm for PsA, although this observation will need to be confirmed with larger numbers. In conclusion, our data provide real-life evidence of the short-term efficacy of apremilast in the treatment of active PsA and suggest that this may be enhanced in earlier disease stages. Apremilast represents a valuable additional oral synthetic molecule for the treatment of PsA. Larger observational cohort studies with health economic evaluations will help confirm the placing of apremilast in the treatment algorithm for PsA. Acknowledgements G.A. was supported by a grant from the Fondazione Italiana per la Ricerca sull’Artrite (FIRA ONLUS). The research was supported by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: H.M.O. has received grants and/or honoraria from AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. G.A. has received honoraria from Celgene, UCB, Pfizer, Italfamaco, Actelion and MSD. D.M.G. has undertaken research and/or educational programme activity with Pfizer, MSD, AbbVie, Bristol-Meyers Squibb, UCB, Novartis, Celgene and Johnson & Johnson. All other authors have declared no conflicts of interest. References 1 Papp K , Reich K, Leonardi CL et al.   Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM 1]). J Am Acad Dermatol  2015; 73: 37– 49. http://dx.doi.org/10.1016/j.jaad.2015.03.049 Google Scholar CrossRef Search ADS PubMed  2 Paul C , Cather J, Gooderham M et al.   Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe plaque psoriasis over 52 weeks: a phase III, randomized, controlled trial (ESTEEM 2). Br J Dermatol  2015; 173: 1387– 99. http://dx.doi.org/10.1111/bjd.14164 Google Scholar CrossRef Search ADS PubMed  3 Schett G , Wollenhaupt J, Papp K et al.   Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum  2012; 64: 3156– 67. http://dx.doi.org/10.1002/art.34627 Google Scholar CrossRef Search ADS PubMed  4 Kavanaugh A , Mease PJ, Gomez-Reino JJ et al.   Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis  2014; 73: 1020. http://dx.doi.org/10.1136/annrheumdis-2013-205056 Google Scholar CrossRef Search ADS PubMed  5 Cutolo M , Myerson GE, Fleischmann RM et al.   A phase III, randomized, con- trolled trial of apremilast in patients with psoriatic arthritis: results of the PALACE 2 trial. J Rheumatol  2016; 43: 1724– 34. http://dx.doi.org/10.3899/jrheum.151376 Google Scholar CrossRef Search ADS PubMed  6 Edwards CJ , Blanco FJ, Crowley J et al.   Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis  2016; 75: 1065– 73. http://dx.doi.org/10.1136/annrheumdis-2015-207963 Google Scholar CrossRef Search ADS PubMed  7 Taylor W , Gladman D, Helliwell P et al.   Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum  2006; 54: 2665– 73. http://dx.doi.org/10.1002/art.21972 Google Scholar CrossRef Search ADS PubMed  8 Mease PJ , Goffe BS, Metz J et al.   Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet  2000; 356: 385– 90. http://dx.doi.org/10.1016/S0140-6736(00)02530-7 Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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RheumatologyOxford University Press

Published: Mar 1, 2018

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