Background/Purpose: Apremilast (APR) is an oral phosphodiesterase 4 inhibitor that helps regulate the immune responses that cause joint inflammation and other manifestations of psoriatic arthritis (PsA), including skin disease. The primary findings from the PALACE 4 study (NCT01307423) demonstrated greater efficacy with APR vs. placebo in disease-modifying anti-rheumatic drug (DMARD)-naïve subjects with active PsA.¹ We describe the long-term efficacy and safety of APR monotherapy in DMARD-naïve subjects in PALACE 4 for up to 208 weeks.

Methods: Subjects were randomized (1:1:1) to placebo, APR 30 mg BID (APR30), or APR 20 mg BID (APR20). At Week 16, subjects were eligible for early escape. At Week 24, all subjects remaining on placebo were switched to APR. Double-blind treatment continued to Week 52, with open-label APR treatment for up to 4 additional years; subjects randomized to APR30 or APR20 continued with their assigned dose during open-label treatment.

Results: A total of 527 subjects were randomized and received ≥1 dose of placebo (n=176), APR30 (n=176), or APR20 (n=175). Of the subjects entering the fourth year of treatment, 92.6% (250/270) completed the Week 208 visit. At Week 52, 58.0% (119/205) of subjects receiving APR30 achieved a ≥20% improvement in modified American College of Rheumatology (ACR20) response. At Week 208, rates of improvement in PsA signs and symptoms and physical function were sustained (Table). Of the subjects still receiving study drug, 68.2%, 43.4%, and 23.1% achieved a modified ACR20, ACR50, and ACR70 response, respectively; 40.5% and 67.6% achieved ≥75% and ≥50% reduction from baseline Psoriasis Area and Severity Index (PASI-75 and PASI-50) responses, respectively (Table). During Weeks >156 to ≤208, the most common adverse events (AEs) among APR30-exposed subjects were upper respiratory tract infection (4.3%) and nasopharyngitis (6.5%); serious AEs occurred in 5.8% of APR30 subjects; serious infection was reported by 1 APR30 subject and no opportunistic infections were reported during Week >156 to ≤208. In general, no change in the types of AEs and no increase in the incidence and severity of AEs were seen with longer-term exposure. The APR20 safety profile was similar to that of APR30.

Conclusion: Over 208 weeks, APR monotherapy demonstrated sustained response and improvements in PsA signs and symptoms, including swollen and tender joint counts, enthesitis, dactylitis, physical function, and psoriasis. APR continued to demonstrate an acceptable safety profile and was generally well tolerated.

Reference: 1. Wells et al. Arthritis Rheum. 2014;66(10 Suppl):S264-5. Abstract 602.