Article
Apremilast, an oral phosphodiesterase 4 inhibitor, is associated with long-term (52-week) improvement in swollen and tender joint counts in patients with Psoriatic Arthritis: Results From Three Phase 3, Randomized, Controlled Trials
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Authors
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Jürgen Wollenhaupt
- Schön Klinik Hamburg Eilbek, Klinik für Rheumatologie und klinische Immunologie, Hamburg
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Georg Schett
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Rheumatologie und Immunologie, Erlangen
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Maurizio Cutolo
- Universita degli Studi di Genova, Genova, Italy
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Philip Mease
- Swedish Medical Center and University of Washington, Seattle, United States of America
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D. Gladman
- Toronto Western Hospital, Toronto Western Research Institute, Division of Health Care and Outcomes Research, Toronto, Canada
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Arthur Kavanaugh
- UCSD, Division of Rheumatology, Allergy and Immunology, La Jolla, United States of America
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Adewale Adebajo
- University of Sheffield, Sheffield, United Kingdom
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Juan Jesús Gomez-Reino
- Hospital Clinico Universitario, Medical School, Universidad de Santiago de Compostela, Rheumatologie, Santiago de Compostela, Spanien
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Eric Lespessailles
- Centre Hospitalier Régional d'Orléans, Rhumatologie, Orléans, France
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Kamal Shah
- Celgene, Drug safety, Warren, United States of America
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ChiaChi Hu
- Celgene Corporation,, Warren, USA
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Randal Stevens
- Celgene Corporation, Summit, NJ, United States of America
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Christopher Edwards
- Southampton University Hospitals NHS Trust, Southampton General Hospital, Department of Rheumatology, Southampton, United Kingdom
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Charles A. Birbara
- UMASS Univesity of Massachusetts Medical school, Worcester, MA, United States of America
| Published: | September 12, 2014 |
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Outline
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Background: Apremilast, an oral phosphodiesterase 4 inhibitor, works intracellularly to modulate inflammatory mediators. The PALACE 1, 2, and 3 trials compared the efficacy and safety of apremilast with placebo in patients with active PsA despite prior conventional DMARDs and/or biologics.
Methods: Patients were randomized (1:1:1) to placebo, apremilast 20 mg BID (APR20), or apremilast 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). Patients whose swollen and tender joint counts (SJC/TJC) had not improved by ≥20% at Week 16 were considered non-responders and were required to be re-randomized (1:1) to APR20 or APR30 if initially randomized to placebo, or continued on their initial apremilast dose. At Week 24, all remaining placebo patients were re-randomized to APR20 or APR30.). SJC and TJC were examined across the 3 trials.
Results: Apremilast resulted in statistically significant and clinically meaningful improvements in ACR20 response (primary endpoint) in all 3 PALACE trials. Median percent reductions (improvements) in SJC and TJC in the intent-to-treat population were statistically significant vs. placebo at Week 16 in all 3 trials. In patients receiving apremilast from baseline, improvements in SJC and TJC were observed at Week 52, with SJC improvements with APR20 and APR30 of -78.8 and -77.8% (PALACE 1),
-87.5% and -87.5% (PALACE 2), and -80.0% and -79.2% (PALACE 3), and TJC improvements of -69.2% and -62.5% (PALACE 1), -58.3% and 63.1% (PALACE 2), and -66.7% and -70.0% (PALACE 3), respectively. The most common AEs reported in patients treated with apremilast for up to 24 weeks (PALACE 1-3, pooled) were diarrhea (12.2%), nausea (10.1%), and headache (8.0%). The safety profile of apremilast through 52 weeks was similar to that observed with apremilast for up to 24 weeks of treatment.
Conclusion: Over 52 weeks, apremilast continued to demonstrate efficacy in the treatment of PsA, including clinically meaningful improvements in SJC and TJC. Apremilast demonstrated an acceptable safety profile and was generally well-tolerated through 52 weeks.
