title: Longterm (52-week) results of a phase III randomized, controlled trial of apremilast in patients with psoriatic arthritis.
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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  NCT01172938.
authors.affiliation: 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.
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.affiliation: 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.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mease
authors.affiliation: 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.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gomez-Reino
authors.affiliation: 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.
authors.forename: Adewale O
authors.initials: AO
authors.lastname: Adebajo
authors.affiliation: 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.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wollenhaupt
authors.affiliation: 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.
authors.forename: Dafna D
authors.initials: DD
authors.lastname: Gladman
authors.affiliation: 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.
authors.forename: Marla
authors.initials: M
authors.lastname: Hochfeld
authors.affiliation: 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.
authors.forename: Lichen L
authors.initials: LL
authors.lastname: Teng
authors.affiliation: 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.
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.affiliation: 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.
authors.forename: Eric
authors.initials: E
authors.lastname: Lespessailles
authors.affiliation: 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.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hall
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058988:Phosphodiesterase 4 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D058988:Phosphodiesterase 4 Inhibitors; D013792:Thalidomide; C505730:apremilast
keywords: APREMILAST; PHOSPHODIESTERASE 4 INHIBITOR; PSORIATIC ARTHRITIS; SAFETY; TREATMENT EFFICACY