Background/Purpose: Apremilast (APR) is a phosphodiesterase 4 inhibitor that helps regulate the immune response that causes inflammation and skin disease associated with psoriatic arthritis (PsA). PALACE 4 compared APR efficacy and safety with placebo in patients with active PsA who were DMARD-naïve. We evaluated the impact of APR over 52 weeks on physical function among PALACE 4 patients.

Methods: Patients were randomized (1:1:1) to placebo, APR 20 mg BID (APR20), or APR 30 mg BID (APR30). 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 for Weeks 0 to 52. Physical function was evaluated using the Health Assessment Questionnaire-Disability Index (HAQ-DI) and 36-item Short-Form Health Survey version 2 (SF-36v2) Physical Function (PF) domain and physical component summary (PCS) scores. Proportions of patients initially randomized to APR achieving minimum clinically important difference (MCID) thresholds at Week 52 for HAQ-DI (≥0.13 or ≥0.30)^1,2 and SF-36v2 PF and PCS (both ≥2.5)³ were determined.

Results: At Week 16, a significantly greater proportion of patients treated with APR achieved a modified ACR20 response vs placebo (primary endpoint). Mean changes in HAQ-DI at Week 16 (key secondary endpoint) were 0.03 (placebo), -0.17 (APR20; P=0.0008), and -0.21 (APR30; P<0.0001). Among patients who were treated with APR continuously through 52 weeks, sustained improvement in HAQ-DI was observed. Mean change in HAQ-DI was -0.32 (APR20) and -0.39 (APR30) at Week 52, exceeding MCID thresholds of ≥0.13 or ≥0.30 (Table). At Week 52, 56.8% (APR20) and 59.0% (APR30) achieved HAQ-DI MCID ≥0.13 and 48.5% and 48.9% achieved MCID ≥0.30, respectively. Week 52 mean changes from baseline in SF-36v2 PF (APR20: 4.61; APR30: 6.41) and PCS (APR20: 5.55; APR30: 6.67) exceeded the MCID threshold (≥2.5). At Week 52, 57.6% of APR20 and APR30 patients achieved SF-36v2 PF MCID, and 60.6% (APR20) and 69.1% (APR30) achieved SF-36v2 PCS MCID. The most common adverse events reported during the placebo-controlled period were nausea (12.6%), diarrhea (9.4%), and headache (6.0%). The safety profile of APR for up to 52 weeks was similar to that observed with APR for up to 24 weeks of treatment (placebo-controlled period).

Conclusion: Over 52 weeks, APR continued to demonstrate clinically meaningful improvements in physical function in active PsA patients who were DMARD-naive. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 weeks.