Article
A Phase 3, Randomized, Controlled Trial of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, for Treatment of Psoriatic Arthritis: Long-term (52-Week) Improvements in Physical Function
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Authors
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Alvin F. Wells
- Rheumatology and Immunotherapy Center, Franklin, WI, USA, Franklin, USA
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Georg Schett
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Rheumatologie und Immunologie, Erlangen
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Adewale Adebajo
- University of Sheffield, Sheffield, United Kingdom
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Alan Kivitz
- Altoona Center for Clinical Research, Duncansville, United States of America
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ChiaChi Hu
- Celgene Corporation,, Warren, USA
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Christopher Edwards
- Southampton University Hospitals NHS Trust, Southampton General Hospital, Department of Rheumatology, Southampton, United Kingdom
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Paul Bird
- University of New South Wales, Kogarah, Australia, Kogarah, Australia
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Jacob A. Aelion
- West Tennessee Research Institute, Jackson, TN, USA, Jackson, USA
| Published: | September 1, 2015 |
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Outline
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Introduction: Apremilast (APR), an oral phosphodiesterase 4 inhibitor, helps regulate the immune responses in psoriatic arthritis (PsA). PALACE 4 compared the efficacy and safety of APR 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 30 mg BID (APR30), or APR 20 mg BID (APR20). The placebo-controlled phase continued to Week 24, with an early escape option at Week 16. Double-blind APR treatment continued to Week 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 Functioning (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 (≥0.30) and SF-36v2 PF and PCS (both ≥2.5) were determined.
Results: At Week 16, a significantly greater proportion of APR-treated patients achieved a modified ACR20 response vs. placebo (primary endpoint). Mean changes in HAQ-DI at Week 16 were 0.03 (placebo), -0.21 (APR30; P<0.0001), and -0.17 (APR20; P=0.0008). At Week 52, sustained improvements in HAQ-DI were observed in patients continuously treated with APR. Mean changes in HAQ-DI were -0.39 (APR30) and -0.32 (APR20) at Week 52, exceeding MCID thresholds of ≥0.30. At Week 52, 48.9% (APR30) and 48.5% (APR20) of patients achieved HAQ-DI MCID of change ≥0.30. Week 52 mean changes from baseline in SF-36v2 PF (APR30: 6.41; APR20: 4.61) and PCS (APR30: 6.67; APR20: 5.55) exceeded the MCID threshold (≥2.5). At Week 52, 57.6% (APR30 and APR20) of patients achieved SF-36v2 PF MCID, and 69.1% (APR30) and 60.6% (APR20) achieved SF-36v2 PCS MCID. The safety profile of APR for up to 52 weeks was similar to that observed 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 patients with active PsA who were DMARD-naive. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 weeks.
