Article
Apremilast, an Oral Phosphodiesterase 4 Inhibitor, Is Associated With Long-term (52-Week) Improvement in Measures of Disease Activity in Patients With Psoriatic Arthrithis: Results From 3 Phase 3, Randomized, Controlled Trials
Search Medline for
Authors
-
Arthur Kavanaugh
- UCSD, Division of Rheumatology, Allergy and Immunology, La Jolla, United States of America
-
Jürgen Wollenhaupt
- Schön Klinik Hamburg Eilbek, Klinik für Rheumatologie und klinische Immunologie, Hamburg
-
Maurizio Cutolo
- Universita degli Studi di Genova, Genova, Italy
-
Philip Mease
- Swedish Medical Center and University of Washington, Seattle, United States of America
-
D. Gladman
- Toronto Western Hospital, Toronto Western Research Institute, Division of Health Care and Outcomes Research, Toronto, Canada
-
Adewale Adebajo
- University of Sheffield, Sheffield, United Kingdom
-
Juan Jesús Gomez-Reino
- Hospital Clinico Universitario, Medical School, Universidad de Santiago de Compostela, Rheumatologie, Santiago de Compostela, Spanien
-
Georg Schett
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Rheumatologie und Immunologie, Erlangen
-
Eric Lespessailles
- Centre Hospitalier Régional d'Orléans, Rhumatologie, Orléans, France
-
ChiaChi Hu
- Celgene Corporation,, Warren, USA
-
Christopher Edwards
- Southampton University Hospitals NHS Trust, Southampton General Hospital, Department of Rheumatology, Southampton, United Kingdom
-
Charles A. Birbara
- UMASS Univesity of Massachusetts Medical school, Worcester, MA, United States of America
| Published: | September 1, 2015 |
|---|
Outline
Text
Introduction: Apremilast (APR), a phosphodiesterase 4 inhibitor, helps regulate immune responses in psoriatic arthritis (PsA). PALACE 1-3 compared APR efficacy and safety with placebo in patients with active PsA despite prior conventional DMARDs and/or biologics, including biologic failures. We report data over 52 weeks.
Methods: Patients were randomized (1:1:1) to placebo, APR 30 mg BID (APR30), or APR 20 mg BID (APR20) stratified by baseline DMARD use (yes/no). 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 they were 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. PsA disease activity was evaluated using a modified ACR20 response, DAS-28 (CRP), MASES, dactylitis count, and PASI-75 response.
Results: At Week 16, significantly more patients treated with APR achieved a modified ACR20 response vs. placebo (primary endpoint). Patients initially randomized to APR and completing 52 weeks had sustained ACR20 responses over 52 weeks (APR30/APR20: 54.6%/63.0% [PALACE 1], 52.6%/52.9% [PALACE 2], 63.0%/56.0% [PALACE 3]). APR30 and APR20 demonstrated sustained improvement in disease activity at Week 52, as measured by mean change in DAS-28 (CRP) (APR30/APR20: -1.31/-1.40 [PALACE 1], -1.30/-1.11 [PALACE 2], -1.41/-1.21 [PALACE 3]); achievement of DAS-28 <2.6 (APR30/APR20: 23.3%/32.5% [PALACE 1], 17.8%/28.0% [PALACE 2], 29.9%/28.1% [PALACE 3]); mean percent changes in MASES (APR30/APR20: -41.0%/-66.0% [PALACE 1], -48.9%/-26.8% [PALACE 2], -40.3%/-40.7% [PALACE 3]); mean percent changes in dactylitis score (APR30/APR20: -37.4%/-74.8% [PALACE 1], -72.1%/-63.1% [PALACE 2], -81.7%/-76.6% [PALACE 3]); PASI-75 response rates (APR30/APR20: 36.8%/24.5% [PALACE 1], 39.3%/27.1% [PALACE 2], 39.1%/28.6% [PALACE 3]); and EULAR good/moderate response rates (APR30/APR20: 74.4%/75.0% [PALACE 1], 67.5%/68.0% [PALACE 2], 74.8%/69.4% [PALACE 3]). The safety profile of APR through 52 weeks was similar to that observed with APR for up to 24 weeks of treatment (placebo-controlled period).
Conclusion: APR demonstrated sustained clinically meaningful improvements in measures of PsA disease activity through Week 52. APR demonstrated an acceptable safety profile and was generally well tolerated through 52 weeks.
