Article
Long-term safety and tolerability of Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with Psoriatic Arthritis: Pooled safety analysis of three phase 3, randomized, controlled trials
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Authors
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Jürgen Braun
- Rheumazentrum Ruhrgebiet, St. Josefs-Krankenhaus, Herne
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Adewale Adebajo
- University of Sheffield, Sheffield, United Kingdom
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Philip Mease
- Swedish Medical Center and University of Washington, Seattle, United States of America
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Arthur Kavanaugh
- UCSD, Division of Rheumatology, Allergy and Immunology, La Jolla, 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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Juan Jesús Gomez-Reino
- Hospital Clinico Universitario, Medical School, Universidad de Santiago de Compostela, Rheumatologie, Santiago de Compostela, Spanien
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Jürgen Wollenhaupt
- Schön Klinik Hamburg Eilbek, Klinik für Rheumatologie und klinische Immunologie, Hamburg
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Maurizio Cutolo
- Universita degli Studi di Genova, Genova, Italy
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Georg Schett
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Rheumatologie und Immunologie, Erlangen
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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 (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to modulate inflammatory mediators. The multicenter clinical trials, PALACE 1, 2, and 3, compared the efficacy/safety of APR vs. placebo in patients with active PsA despite prior conventional DMARDs and/or biologics.
Methods: Patients were randomized (1:1:1) to placebo, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). Patients whose SJC and 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 APR dose. At Week 24, remaining placebo patients were re-randomized to APR20 or APR30 through Week 52.
Results: 1,493 patients received study medication (placebo: 495; APR20: 501; APR30: 497) and comprised the safety population. The APR-exposure period included 720 patients receiving APR20 (766.4 patient-years) and 721 receiving APR30 (769.0 patient-years). The nature, incidence, and severity of AEs were comparable through the 24-week and 52-week APR-exposure periods. The most common AEs in patients receiving APR for up to 24 weeks (PALACE 1-3, pooled) were diarrhea (12.2%), nausea (10.1%), and headache (8.0%). Of patients with AEs, the majority (>90%) were mild or moderate in severity. Discontinuations due to AEs (APR20: 7.5%; APR30: 8.3%) were low. SAEs occurred in 6.8% (APR20) and 7.2% (APR30) of patients. One death occurred (APR20) due to multiorgan failure not suspected to be treatment-related. Diarrhea and nausea were predominantly mild. Discontinuation due to gastrointestinal AEs was 4% through Week 52. Exposure-adjusted incidence rates of major adverse cardiac events (MACE), serious infections, and malignancies were comparable to placebo. Laboratory abnormalities were infrequent and transient with no trends or patterns observed.
Conclusion: APR was generally well-tolerated through 52 weeks; the nature, incidence, and severity of AEs did not change with longer exposure. These data do not indicate a need for laboratory monitoring.
