THU0294 5-year efficacy and safety of apremilast treatment in subjects with psoriatic arthritis: pooled analysis of the palace studies
Authors: A. Kavanaugh, D.D. Gladman, C.J. Edwards, G. Schett, B. Guerette, N. Delev, L. Teng, M. Paris, P.J. Mease
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Apremilast (APR) is an oral phosphodiesterase 4 inhibitor for the treatment of adult patients with active psoriatic arthritis (PsA). <h3>Objectives</h3> The long-term efficacy and safety of APR treatment were evaluated for up to 5 years in subjects with active PsA from the phase 3 PALACE 1, 2, and 3 studies. <h3>Methods</h3> Subjects were randomised at baseline (BL) (1:1:1) to receive placebo (PBO), APR 30 mg BID (APR30), or APR 20 mg BID (APR20). PBO subjects were re-randomised (1:1) to APR30 or APR20 at Week 16 (early escape) or Week 24. Double-blind APR treatment continued to Week 52; subjects could continue APR during an open-label, long-term treatment phase for up to 5 years. Safety was assessed at each visit throughout the study. <h3>Results</h3> A total of 1493 subjects were randomised and received ≥1 dose of study medication (PBO: n=495; APR30: n=497; APR20: n=501). Of those randomised to APR30 at BL, 66.6% (331/497) completed 260 weeks of treatment. At Week 52, modified ACR20, ACR50, and ACR70 responses were achieved by 55.3%, 26.1%, and 11.9% of APR30 subjects, respectively, regardless of when APR was started (BL, Week 16, or Week 24). Sustained response rates were observed with continued APR30 treatment at Week 260 (table 1). Marked SJC improvements were seen, with mean percent reduction of 82.3% at Week 260; TJC reduction was 72.7%. At Week 260, 62.4% (136/218) of APR30 subjects with BL enthesitis achieved a MASES of 0; 80.9% (114/141) with BL dactylitis achieved a dactylitis count of 0. A total of 52.6% of APR30 subjects achieved HAQ-DI MCID ≥0.35 at Week 260, and low disease activity and remission, as defined by the cDAPSA (score ≤13), were achieved by 60.4% of APR30 subjects. Sustained responses in psoriatic skin involvement were observed with continued treatment at Week 260 in APR30 subjects who had ≥3% BL psoriasis body surface area involvement, with PASI-50 and PASI-75 response rates of 65.8% (98/149) and 43.6% (65/149), respectively. Results were similar for subjects receiving APR20 (data not shown). Consistent efficacy results were seen across the 3 individual trials. No new safety concerns were identified with APR up to 260 weeks. For APR30 subjects entering the 5th year of APR exposure, adverse events (AEs) occurring in ≥5% were nasopharyngitis (6.6%) and upper respiratory tract infections (5.8%); most AEs were mild or moderate in severity. Among APR30-exposed subjects, serious AEs occurred in 5.8% in Weeks&gt;208 to≤260; 5 subjects discontinued due to an AE. <h3>Table 1</h3> <h3>Conclusions</h3> APR demonstrated sustained, clinically meaningful improvements in PsA signs and symptoms, physical function, and associated psoriasis in the population of subjects continuing treatment over 5 years. APR continued to demonstrate a favourable safety profile and was generally well tolerated at 5 years. <h3>Disclosure of Interest</h3> A. Kavanaugh Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, and UCB, D. Gladman Grant/research support from: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, and UCB, C. Edwards Grant/research support from: Celgene Corporation; Pfizer, Roche, Samsung, Consultant for: Celgene Corporation, Pfizer, Roche, Samsung, Speakers bureau: Abbott, GSK, Pfizer, Roche, G. Schett Grant/research support from: Abbott, Celgene Corporation, Roche, UCB, Consultant for: Abbott, Celgene Corporation, Roche, UCB, B. Guerette Employee of: Celgene Corporation, N. Delev Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, M. Paris Employee of: Celgene Corporation, P. Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Genentech, Janssen, Eli Lilly, Pfizer, UCB