Background Psoriatic arthritis (PsA) reduces physical function and QoL; a treatment goal is to improve/maintain functionality. PALACE 1 (NCT01172938), 2 (NCT01212757), and 3 (NCT01212770) compared apremilast (APR) efficacy/safety with placebo (PBO) in patients (pts) with active PsA despite prior conventional DMARDs and/or biologics, providing one of the largest databases (N=1,489) examining physical disability in pts with moderate/severe PsA.
Objectives Assess APR 30 mg BID (APR30) treatment impact on disability using the HAQ-DI over 104 wks with PALACE 1–3 pooled data.
Methods Pts were randomized (1:1:1) to PBO, APR30, or APR 20 mg BID (APR20) stratified by baseline (BL) DMARD use (yes/no). At Wk 24, all remaining PBO pts were re-randomized to APR30 or APR20. HAQ-DI scores were collected at BL and Wks 16, 24, 40, 52 65, 78, 91, and 104. Mean change, proportion reaching MCID, and disability levels were calculated; HAQ-DI cutoff levels were ≤1.0 (clinically significant disability1), ≤0.5 (MDA criteria2), and ≤0.25. Score shift categories were examined in 0.25 increments to clarify pt disability level. Wk 16 data, compared with PBO, are analyzed by intent-to-treat/LOCF methodology. Other data shown are as observed to Wk 104. Mean change and MCID outcomes are for all pts receiving treatment with APR30 at any time during the study; for disability level and category shift assessments, data are shown for pts randomized to APR at BL.
Results Pts exhibited significant BL physical disability (mean HAQ-DI=1.2); 60% of APR30 pts had a score >1.0, and 31% >1.5, noting marked difficulty/need for assistive devices in performing activities of daily living. Major disability was noted in 19% with BL HAQ-DI >1.75. As early as Wk 16, physical function improved with APR30; pts exhibited a mean HAQ-DI change of −0.23 (vs −0.08 PBO; P<0.0001), 56% achieved HAQ-DI ≤1.0 at Wk 16 (vs 48% PBO pts), and 29% achieved HAQ-DI ≤0.5 (vs 25% PBO pts). Fewer PBO vs APR30 pts reached the MCID of −0.13 (prespecified analysis; 37% vs 47%; P<0.005) or −0.30 (prespecified analysis)/−0.353 (post hoc analysis) (26% vs 36% for both; P<0.005). At Wk 52, decreases in disability were maintained (APR30 mean change in HAQ-DI=−0.33); 48% of APR30 pts achieved MCID −0.30 and −0.35. Importantly, at Wk 52, 58% of all APR30 pts achieved HAQ-DI ≤1.0, 34% ≤0.5, and 24% ≤0.25 (Table). Among pts with greater BL disability (HAQ-DI ≥1.5), 64% improved by ≥1 shift category and 47% by ≥2. At Wk 104, 50% of APR30 pts achieved MCID of −0.30 and −0.35, with 64% achieving HAQ-DI ≤1.0, 38% ≤0.5, and 28% ≤0.25; LOCF analysis confirmed Wk 104 results.
Conclusions In APR30 pts, physical function improved at Wk 16 and was sustained with long-term treatment. Most pts achieved HAQ-DI MCID −0.30 or −0.35 and HAQ-DI scores ≤1.0, with many obtaining HAQ-DI ≤0.5, defined as minimal disease in recent criteria. These data indicate improvement and long-term maintenance of functionality with APR treatment.
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Disclosure of Interest P. Mease Grant/research support from: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, UCB, Celgene Corporation, Novartis, Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, UCB, Celgene Corporation, Novartis, Roche, J. Wollenhaupt Grant/research support from: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, Consultant for: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, S. Hall Grant/research support from: Celgene Corporation, Pfizer, UCB, Bristol-Myers Squibb, Glaxo-Smith Kline, Roche, Janssen, Novartis, Merck, Consultant for: Celgene Corporation, Pfizer, UCB, Bristol-Myers Squibb, Glaxo-Smith Kline, Roche, Janssen, Novartis, Merck, F. Van den Bosch Grant/research support from: Celgene Corporation, E. Lespessailles Grant/research support from: Amgen, Celgene, Eli Lilly, Novartis, and Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, and Servier, M. McIlraith Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, C. Edwards Grant/research support from: Celgene Corporation, Pfizer Inc, Roche, Samsung, Consultant for: Celgene Corporation, Pfizer Inc, Roche, Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, Roche