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 (PBO) in patients with active PsA despite prior conventional disease-modifying antirheumatic drugs (DMARDs) and/or biologics, including biologic failures. We evaluated the impact of APR over 52 weeks on PsA disease activity.

Methods: Patients were randomized (1:1:1) to receive PBO, 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 PBO, or continued on their initial APR dose. At Week 24, all remaining PBO patients were re-randomized to APR20 or APR30. This analysis reports data over 52 weeks. Disease activity was evaluated using a modified American College of Rheumatology 20 (ACR20) response, 28-joint count Disease Activity Scale (DAS-28; C-reactive protein [CRP]), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), dactylitis count, and 75% reduction from baseline Psoriasis Area and Severity Index (PASI-75) response.

Results: At Week 16, a significantly greater proportion of patients treated with APR achieved a modified ACR20 response vs PBO (primary endpoint). In patients initially randomized to APR and completing 52 weeks, ACR20 response was sustained over 52 weeks. APR20 and APR30 demonstrated improvement in disease activity vs PBO at Week 16, as measured by the mean change in DAS-28 (CRP), achievement of DAS-28 <2.6, median percent changes in MASES/dactylitis score, and PASI-75 response. Among patients who were continuously treated with APR through 52 weeks, sustained improvements were observed at Week 52 (Table). The most common adverse events reported during the PBO-controlled period (PALACE 1-3; pooled) were diarrhea (12.2%), nausea (10.1%), and headache (8.0%). The safety profile of APR through 52 weeks was similar to that observed with APR for up to 24 weeks of treatment (PBO-controlled period). Marked laboratory abnormalities generally were infrequent and returned to baseline with continued treatment or were associated with a concurrent medical condition.

Conclusion: APR demonstrated sustained clinically meaningful improvements in measures of PsA disease activity through Week 52. APR demonstrated an acceptable safety profile and was generally well tolerated through 52 weeks.