Arthur Kavanaugh1, Philip J Mease2, Juan J Gomez-Reino2, Adewale O Adebajo2, Jürgen Wollenhaupt2, Dafna D Gladman2, Marla Hochfeld2, Lichen L Teng2, Georg Schett2, Eric Lespessailles2, Stephen Hall2. 1. From the University of California, San Diego School of Medicine, La Jolla, California; Swedish Medical Center and University of Washington School of Medicine, Seattle, Washington; Celgene Corporation, Summit, New Jersey, USA; University of Sheffield, Sheffield, UK; Hospital Clinico Universitario, Santiago, Spain; Schön Klinik Hamburg Eilbek, Hamburg; University of Erlangen-Nuremberg, Erlangen, Germany; Toronto Western Research Institute, Toronto, Ontario, Canada; University of Orléans, Orléans, France; and the Monash University, Cabrini Health Australia, Melbourne, Australia.A. Kavanaugh, MD, Division of Rheumatology, Allergy and Immunology, University of California; P.J. Mease, MD, Swedish Hospital Clinical Research Division, Swedish Medical Center, and Clinical Professor, University of Washington School of Medicine; J.J. Gomez-Reino, MD, PhD, Rheumatology Service, Department of Medicine, Hospital Clinico Universitario; A.O. Adebajo, MD, FRCP, Professor of Rheumatology, Faculty of Medicine, Dentistry and Health, University of Sheffield; Prof. Dr. med. J. Wollenhaupt, Schön Klinik Hamburg Eilbek, Klinik für Rheumatologie; D.D. Gladman, MD, FRCPC, Division of Health Care and Outcomes Research, Toronto Western Research Institute; M. Hochfeld, MD; L.L. Teng, PhD, Celgene Corporation; Prof. Dr. med. G. Schett, Department of Internal Medicine, University of Erlangen-Nuremberg; E. Lespessailles, MD, PhD, University of Orléans; S. Hall, MBBS, FRACP, Associate Professor of Medicine, Monash University, Cabrini Health Australia. akavanaugh@ucsd.edu. 2. From the University of California, San Diego School of Medicine, La Jolla, California; Swedish Medical Center and University of Washington School of Medicine, Seattle, Washington; Celgene Corporation, Summit, New Jersey, USA; University of Sheffield, Sheffield, UK; Hospital Clinico Universitario, Santiago, Spain; Schön Klinik Hamburg Eilbek, Hamburg; University of Erlangen-Nuremberg, Erlangen, Germany; Toronto Western Research Institute, Toronto, Ontario, Canada; University of Orléans, Orléans, France; and the Monash University, Cabrini Health Australia, Melbourne, Australia.A. Kavanaugh, MD, Division of Rheumatology, Allergy and Immunology, University of California; P.J. Mease, MD, Swedish Hospital Clinical Research Division, Swedish Medical Center, and Clinical Professor, University of Washington School of Medicine; J.J. Gomez-Reino, MD, PhD, Rheumatology Service, Department of Medicine, Hospital Clinico Universitario; A.O. Adebajo, MD, FRCP, Professor of Rheumatology, Faculty of Medicine, Dentistry and Health, University of Sheffield; Prof. Dr. med. J. Wollenhaupt, Schön Klinik Hamburg Eilbek, Klinik für Rheumatologie; D.D. Gladman, MD, FRCPC, Division of Health Care and Outcomes Research, Toronto Western Research Institute; M. Hochfeld, MD; L.L. Teng, PhD, Celgene Corporation; Prof. Dr. med. G. Schett, Department of Internal Medicine, University of Erlangen-Nuremberg; E. Lespessailles, MD, PhD, University of Orléans; S. Hall, MBBS, FRACP, Associate Professor of Medicine, Monash University, Cabrini Health Australia.
Abstract
OBJECTIVE: To evaluate the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, over 52 weeks in patients with active psoriatic arthritis (PsA) despite prior treatment. METHODS: Patients were randomized to placebo (n = 168), apremilast 20 mg BID (n = 168), or apremilast 30 mg BID (n = 168). Patients whose swollen and tender joint counts had not improved by ≥ 20% at Week 16 were considered nonresponders and were required to be re-randomized (1:1) to apremilast 20 mg BID or 30 mg BID if they were initially randomized to placebo, or continued their initial treatment of apremilast dose. At Week 24, all remaining patients treated with placebo were re-randomized to apremilast 20 mg BID or 30 mg BID. RESULTS: An American College of Rheumatology 20 (ACR20) response at Week 16 was attained by significantly more patients receiving apremilast 20 mg BID (30.4%, p = 0.0166) or 30 mg BID (38.1%, p = 0.0001) than placebo (19.0%). Among patients receiving apremilast continuously for 52 weeks (n = 254), ACR20 response at Week 52 was observed in 63.0% (75/119, 20 mg BID) and 54.6% (71/130, 30 mg BID) of patients. Response was also maintained across secondary outcomes, including measures of PsA signs and symptoms, skin psoriasis severity, and physical function. The nature, incidence, and severity of adverse events were comparable over the 24-week and 52-week periods. The most common adverse events, diarrhea and nausea, generally occurred early and were self-limited. CONCLUSION: Continuous apremilast treatment resulted in sustained improvements in PsA for up to 52 weeks. Apremilast had an acceptable safety profile and was generally well tolerated. CLINICAL TRIAL REGISTRATION: NCT01172938.
RCT Entities:
OBJECTIVE: To evaluate the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, over 52 weeks in patients with active psoriatic arthritis (PsA) despite prior treatment. METHODS:Patients were randomized to placebo (n = 168), apremilast 20 mg BID (n = 168), or apremilast 30 mg BID (n = 168). Patients whose swollen and tender joint counts had not improved by ≥ 20% at Week 16 were considered nonresponders and were required to be re-randomized (1:1) to apremilast 20 mg BID or 30 mg BID if they were initially randomized to placebo, or continued their initial treatment of apremilast dose. At Week 24, all remaining patients treated with placebo were re-randomized to apremilast 20 mg BID or 30 mg BID. RESULTS: An American College of Rheumatology 20 (ACR20) response at Week 16 was attained by significantly more patients receiving apremilast 20 mg BID (30.4%, p = 0.0166) or 30 mg BID (38.1%, p = 0.0001) than placebo (19.0%). Among patients receiving apremilast continuously for 52 weeks (n = 254), ACR20 response at Week 52 was observed in 63.0% (75/119, 20 mg BID) and 54.6% (71/130, 30 mg BID) of patients. Response was also maintained across secondary outcomes, including measures of PsA signs and symptoms, skin psoriasis severity, and physical function. The nature, incidence, and severity of adverse events were comparable over the 24-week and 52-week periods. The most common adverse events, diarrhea and nausea, generally occurred early and were self-limited. CONCLUSION: Continuous apremilast treatment resulted in sustained improvements in PsA for up to 52 weeks. Apremilast had an acceptable safety profile and was generally well tolerated. CLINICAL TRIAL REGISTRATION: NCT01172938.
Authors: Jasvinder A Singh; Gordon Guyatt; Alexis Ogdie; Dafna D Gladman; Chad Deal; Atul Deodhar; Maureen Dubreuil; Jonathan Dunham; M Elaine Husni; Sarah Kenny; Jennifer Kwan-Morley; Janice Lin; Paula Marchetta; Philip J Mease; Joseph F Merola; Julie Miner; Christopher T Ritchlin; Bernadette Siaton; Benjamin J Smith; Abby S Van Voorhees; Anna Helena Jonsson; Amit Aakash Shah; Nancy Sullivan; Marat Turgunbaev; Laura C Coates; Alice Gottlieb; Marina Magrey; W Benjamin Nowell; Ana-Maria Orbai; Soumya M Reddy; Jose U Scher; Evan Siegel; Michael Siegel; Jessica A Walsh; Amy S Turner; James Reston Journal: Arthritis Rheumatol Date: 2018-11-30 Impact factor: 10.995