Background/Purpose: Apremilast (APR) is an oral phosphodiesterase 4 inhibitor that helps regulate the immune response that causes inflammation and skin disease associated with psoriatic arthritis (PsA). The PALACE 1, 2, and 3 trials compared the efficacy and safety of APR with placebo in patients with active PsA despite prior conventional disease-modifying antirheumatic drugs (DMARDs) and/or biologics, including biologic failures.

Methods: Patients were randomized (1:1:1) to receive placebo, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). Patients whose swollen and tender joint counts had not improved by ≥20% at Week 16 were considered non-responders and were required to be re-randomized (1:1) to APR20 or APR30 if they were initially randomized to placebo, or continued on their initial apremilast dose. At Week 24, all remaining placebo patients were re-randomized to APR20 or APR30. This analysis reports data over 52 weeks.

Results: In the pooled PALACE 1-3 population, a significantly greater proportion of patients receiving APR20 and APR30 achieved a modified ACR20 response vs placebo at Week 16 (placebo: 18.8%; APR20: 32.0% [P<0.0001]; APR30: 37.0% [P<0.0001]) (primary endpoint). At Week 16, significant improvements were observed with APR20 and APR30 (PALACE 1-3, pooled) for multiple patient-reported outcomes compared with placebo (placebo; APR20; and APR30, respectively): least-squares (LS) mean changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) (-0.07; -0.16 [P=0.0009]; and -0.21 [P<0.0001), pain visual analog scale (VAS) (-5.8; -10.7 [P=0.0009]; and -12.7 [P <0.0001]), 36-item Short-Form Health Survey version 2 (SF-36v2) physical component summary (PCS) (1.9; 3.3 [P=0.0016]; and 3.9 [P<0.0001]), and SF-36v2 Physical Functioning (PF) domain (1.3; 2.7 [P=0.0057]; and 3.6 [P<0.0001]) scores. APR30 also significantly improved the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score at Week 16 (1.1; 1.5 [P=NS]; and 3.5 [P<0.0001]). In patients initially randomized to APR who completed Week 52, improvements were sustained at Week 52 across the individual studies (Table). The most common adverse events reported for up to 24 weeks of APR treatment were diarrhea (12.2%), nausea (10.1%), and headache (8.0%) (PALACE 1-3; pooled). The safety profile of APR through 52 weeks was similar to that observed with APR for up to 24 weeks of treatment.

Conclusion: Among patients continuously treated with APR, sustained clinically meaningful improvements in patient-reported outcome measures of pain, physical function, and fatigue were observed through Week 52. APR demonstrated an acceptable safety profile and was generally well tolerated through 52 weeks.