Long‐Term Safety and Tolerability of Apremilast Versus Placebo in Psoriatic Arthritis: A Pooled Safety Analysis of Three Phase III, Randomized, Controlled Trials

Objective Psoriatic arthritis (PsA) requires long‐term treatment, yet safety concerns and monitoring requirements make maintenance a challenge. This analysis of pooled Psoriatic Arthritis Long‐term Assessment of Clinical Efficacy (PALACE) 1, 2, and 3 data describes 3‐year apremilast safety and tolerability in PsA. Methods Patients with active PsA were randomized (1:1:1) to placebo, apremilast 30 mg twice daily, or apremilast 20 mg twice daily. Placebo patients were re‐randomized to apremilast 30 mg twice daily or 20 mg twice daily at week 16 (early escape) or 24. Double‐blind treatment continued to week 52; patients could continue apremilast during an open‐label, long‐term treatment phase. Results In total, 1493 patients received at least one dose of study medication and were included in the safety population (placebo: n = 495; apremilast 30 mg: n = 497; apremilast 20 mg: n = 501). Among patients receiving apremilast, 53.2% (767/1441) completed 3 years of treatment. Greater rates of adverse events (AEs) were reported with apremilast (61.1%; exposure‐adjusted incidence rate [EAIR]/100 patient‐years, 265.1) versus placebo (47.5%; EAIR/100 patient‐years, 200.7) in the placebo‐controlled period. During weeks 0 to ≤52, the most common AEs occurring in apremilast‐exposed patients were diarrhea (13.9%; EAIR/100 patient‐years, 18.6), nausea (12.3%; EAIR/100 patient‐years, 16.0), headache (9.4%; EAIR/100 patient‐years, 12.1), upper respiratory tract infection (9.1%; EAIR/100 patient‐years, 11.5), and nasopharyngitis (6.2%; EAIR/100 patient‐years, 7.7). Most AEs were mild/moderate with apremilast exposure ≤156 weeks. Rates of depression remained low (EAIR/100 patient‐years, 1.8). Major adverse cardiac events (EAIR/100 patient‐years, 0.5), malignancies (EAIR/100 patient‐years, 0.9), and serious opportunistic infections (EAIR/100 patient‐years, 0.0) were infrequent over the 3‐year exposure period. Discontinuation rates due to AEs were low (<7.5%) across all apremilast‐exposure periods. Incidences of clinically meaningful abnormalities in postbaseline laboratory values was low; most values returned to baseline levels with continued treatment and without intervention. Conclusion Apremilast demonstrated a favorable safety profile and was well tolerated up to 156 weeks.