Background/Purpose: Apremilast (APR) is an oral phosphodiesterase 4 inhibitor that helps regulate the immune response that causes joint inflammation and other manifestations of psoriatic arthritis (PsA), including skin disease. PALACE 4 compared the efficacy and safety of APR monotherapy with placebo (PBO) in patients with active PsA who were DMARD-naïve.

Methods: Patients were randomized (1:1:1) to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30). Patients whose swollen and tender joint counts (SJC/TJC) 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. Double-blind treatment continued to Week 52; patients could continue to receive APR during an open-label, long-term safety phase extending up to 4 years. We report the long-term efficacy and safety of apremilast in patients treated for up to 2 years in PALACE 4.

Results: 527 patients were randomized and received ≥1 dose of study medication (PBO: n=176; APR20: n=175; APR30: n=176). At Week 52, a modified ACR20 response was achieved by 53.4% (70/131) and 58.7% (81/138) of patients continually treated with APR20 or APR30 from BL, respectively.; approximately 84% of patients completing 1 year of APR treatment were maintained on therapy at the time of data cutoff during their second year of APR exposure. In patients receiving APR from BL, improvements were sustained over 104 weeks for multiple end points (Table 1), including modified ACR20/ACR50/ACR70 responses, median % change in SJC/TJC, mean change in HAQ-DI, % of patients with HAQ-DI exceeding the MCID threshold of ≥0.30, MASES, dactylitis severity scores, and PASI-50/PASI-75 responses. Consistent results were demonstrated in patients randomized to PBO at BL and re-randomized to APR20 or APR30 at Week 16 or Week 24 who completed Week 104. Most AEs were mild/moderate in severity between Weeks >52 and ≤104 and in general, no change in the types of AEs and no increase in the incidence or severity of AEs was seen with longer term exposure (Table 2). Diarrhea and nausea occurred at lower rates in Weeks >52 to ≤104 vs Weeks 0 to ≤52.

Conclusion: Over 104 weeks, APR monotherapy demonstrated sustained response and improvements in PsA signs and symptoms, enthesitis, dactylitis, physical function, and psoriasis. The ACR20 response was 57% for patients receiving APR30 therapy for 2 years. APR continued to demonstrate an acceptable safety profile and was generally well tolerated.