Article
Long-term (104-Week) Efficacy and Safety of Apremilast Monotherapy in DMARD-Naive Patients With Psoriatic Arthritis: Results From a Phase III, Randomized, Controlled Trial and Open-Label Extension (PALACE 4)
Search Medline for
Authors
Published: | September 1, 2015 |
---|
Outline
Text
Introduction: Apremilast (APR), an oral phosphodiesterase 4 inhibitor, helps regulate immune responses in psoriatic arthritis (PsA). PALACE 4 compared APR monotherapy efficacy/safety with placebo in DMARD-naïve patients with active PsA.
Methods: Patients were randomized (1:1:1) to placebo, APR 30 mg BID (APR30), or APR 20 mg BID (APR20). 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 APR30 or APR20 if initially randomized to placebo, or continued on their initial APR dose. At Week 24, all remaining placebo patients were re-randomized to APR30 or APR20. Double-blind treatment continued to Week 52; patients could continue receiving APR up to an additional 4 years. We report long-term APR efficacy/safety (≤2 years).
Results: 527 patients were included in the modified intent-to-treat population in which patients who were randomized in error and did not receive study medication were excluded (placebo: n=176; APR30: n=176; APR20: n=175); ≈84% of patients completing Week 52 were maintained on therapy in year 2. At Week 104, APR patients demonstrated sustained improvements, shown by improvements in modified ACR response (20%/50%/70%) rates (APR30: 61.4%/40.7%/19.2%; APR20: 64.2%/41.6%/23.3%); swollen/tender joint count mean percent change (APR30: -79.8/-64.0; APR20: -77.2/-60.9); Health Assessment Questionnaire-Disability Index (HAQ-DI) mean change (APR30: -0.38; APR20: -0.33); proportion of patients with HAQ-DI minimal clinically important differences ≥0.30 (APR30: 48.3%; APR20: 50.6%); Maastricht Ankylosing Spondylitis Enthesitis Score=0 (APR30: 61.4%; APR20: 58.3%); dactylitis count=0 (APR30: 84.7%; APR20: 82.7%); and 75%/50% reduction from baseline Psoriasis Area and Severity Index response (APR30: 35.1%/56.7%; APR20: 44.0%/60.4%). The most common adverse events (AEs) with APR were upper respiratory tract infection (4.8%) and nasopharyngitis (3.2%) (Weeks >52-≤104); 5.3% experienced serious AEs. No change in types of AEs and no increase in AE incidence/severity were seen with longer-term exposure. Diarrhea and nausea rates were lower in Weeks >52-≤104.
Conclusion: Over 104 weeks, APR monotherapy demonstrated sustained response/improvements in PsA signs/symptoms, including enthesitis, dactylitis, physical function, and psoriasis. ACR20 response was 61% (APR30) at 2 years. APR continued to demonstrate an acceptable safety profile and was generally well tolerated.