Background/Purpose: Apremilast (APR), an oral phosphodiesterase 4 inhibitor that may modify the immune response, has been shown effective in psoriatic arthritis (PsA). PALACE 1 compared the efficacy and safety of APR with placebo in patients with active PsA despite prior conventional 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 (SJC and 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 placebo, or continued on their initial apremilast dose. At Week 24, all remaining placebo patients were re-randomized to APR20 or APR30. Double-blind APR treatment continued to Week 52; patients could continue to receive apremilast during an active treatment, long-term phase of up to 4 years, for a total follow-up of up to 5 years. Efficacy in patients randomized to apremilast at baseline and with evaluable data at Week 52 and Week 104 is described herein (analysis: as observed).

Results: 504 patients were randomized and received ≥1 dose of study medication (placebo: n=168; APR20: n=168; APR30: n=168). At Week 52, modified ACR20 response was achieved by 63.0% and 54.6% of patients continually treated with APR20 or APR30 from baseline, respectively. Among patients who were randomized to APR at baseline, 97 APR20 and 101 APR30 patients remained in the study and completed evaluations at Week 104. Approximately 80% of patients who completed year 1 were maintained on therapy at year 2. In patients receiving APR from baseline, improvements were sustained over 104 weeks for multiple endpoints (Table), including (1) modified ACR20/ACR50/ACR70 of 61.3%/29.8%/16.0% (APR20) and 66.3%/35.6%/19.8%, respectively (APR30); (2) median percent change in SJC/TJC of -88.9%/-80.5% (APR20) and -87.5%/-76.7% (APR30); (3) mean change in Health Assessment Questionnaire-Disability Index (HAQ-DI) of -0.33 (APR20) and -0.43 (APR30), and greater than 50% achieving minimal important differences ≥0.30; (4) mean change in 28-joint count Disease Activity Score (DAS-28) of -1.61 (APR20) and -1.83 (APR30); and (5) achievement of DAS <2.6 in 35.1% (APR20) and 38.6% (APR30) of patients. Consistent results were demonstrated in patients randomized to placebo at baseline and re-randomized to APR20 or APR30 at Week 16 or 24 who completed Week 104. No new safety signals were observed with treatment through 104 weeks.

Conclusion: Over 104 weeks, APR demonstrated sustained clinically meaningful improvements in the signs and symptoms of PsA, physical function, and associated skin symptoms. ACR 20 response at Week 104 was 66% for APR 30. APR continued to demonstrate an acceptable safety profile and was generally well tolerated.