Apremilast Long-Term Safety Up to 5 Years from 15 Pooled Randomized, Placebo-Controlled Studies of Psoriasis, Psoriatic Arthritis, and Behçet's Syndrome

Abstract

Background: Since US FDA approval in 2014, apremilast has consistently demonstrated a favorable benefit-risk profile in 706,585 patients (557,379 patient-years of exposure) worldwide across approved indications of plaque psoriasis, psoriatic arthritis, and Behçet's syndrome; however, long-term exposure across these indications has not been reported.

Objective: The aim of this study was to conduct a pooled analysis of apremilast data from 15 clinical studies with open-label extension phases, focusing on long-term safety.

Methods: We analyzed longer-term safety and tolerability of apremilast 30 mg twice daily across three indications for up to 5 years, focusing on adverse events of special interest, including thrombotic events, malignancies, major adverse cardiac events (MACE), serious infections, and depression. Data were pooled across 15 randomized, placebo-controlled studies and divided into placebo-controlled or all-apremilast-exposure groups. Treatment-emergent adverse events (TEAEs) were assessed.

Results: Overall, 4183 patients were exposed to apremilast (6788 patient-years). Most TEAEs were mild to moderate in the placebo-controlled period (96.6%) and throughout all apremilast exposure (91.6%). TEAE rates of special interest were similar between treatment groups in the placebo-controlled period and remained low throughout all apremilast exposure. Exposure-adjusted incidence rates per 100 patient-years during all apremilast exposure were MACE, 0.30; thrombotic events, 0.10; malignancies, 1.0; serious infections, 1.10; serious opportunistic infections, 0.21; and depression, 1.78. Safety findings were consistent across indications and regions. No new safety signals were identified.

Conclusions: The incidence of serious TEAEs and TEAEs of special interest was low despite long-term exposure, further establishing apremilast as a safe oral option for long-term use across indications with a favorable benefit-risk profile.

Clinical trial registration: NCT00773734, NCT01194219, NCT01232283, NCT01690299, NCT01988103, NCT02425826, NCT03123471, NCT03721172, NCT01172938, NCT01212757, NCT01212770, NCT01307423, NCT01925768, NCT00866359, NCT02307513.