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FRI0447 Long-Term (156-Week) Efficacy and Safety Profile of Apremilast, An Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Results from A Phase III, Randomized, Controlled Trial and Open-Label Extension (Palace 1)
  1. A. Kavanaugh1,
  2. D.D. Gladman2,
  3. J.J. Gomez-Reino3,
  4. S. Hall4,
  5. E. Lespessailles5,
  6. P.J. Mease6,
  7. G. Schett7,
  8. M. McIlraith8,
  9. K. Shah8,
  10. L. Teng8,
  11. J. Wollenhaupt9
  1. 1University of California, San Diego, School of Medicine, La Jolla, United States
  2. 2Toronto Western Research Institute, Toronto, Canada
  3. 3Hospital Clinico Universitario, Santiago, Spain
  4. 4Monash University, Melbourne, Australia
  5. 5University of Orléans, Orléans, France
  6. 6Swedish Medical Center and University of Washington School of Medicine, Seattle, United States
  7. 7University of Erlangen-Nuremberg, Erlangen, Germany
  8. 8Celgene Corporation, Summit, United States
  9. 9Schön Klinik Hamburg Eilbek, Hamburg, Germany

Abstract

Background Long-term data on the efficacy and safety of therapies is vital for treatment decision making in chronic diseases such as psoriatic arthritis (PsA). Three-year treatment data from the PALACE 1 (NCT01172938) study of apremilast (APR) in patients with active PsA despite previous conventional disease-modifying antirheumatic drug (DMARD) or biologic therapy has recently become available.

Objectives Using data from 3 years of treatment, examine the longer term efficacy/safety of APR.

Methods Patients were randomized (1:1:1) to placebo (PBO), APR 30 mg BID (APR30), or APR 20 mg BID (APR20) stratified by baseline DMARD use (yes/no). The PBO-controlled phase continued to Wk 24, with an early escape option at Wk 16. At Wk 24, all remaining PBO patients were re-randomized to APR30 or APR20. Double-blind APR treatment continued to Wk 52; patients could continue APR for up to 4 additional years. Efficacy assessments in years 2 and 3 were conducted at Wks 65, 78, 91, 104, 117, 130, 143, and 156.

Results 504 randomized patients received ≥1 dose of study medication (PBO: n=168; APR30: n=168; APR20: n=168). In an “as observed” analysis, 53.2% (APR30) and 59.6% (APR20) of patients achieved a modified ACR20 response at Wk 52 (Table), regardless of when APR was started (baseline, Wk 16, or Wk 24). Of the patients entering year 2, 65.3% (APR30) and 60.9% (APR20) attained these responses at Wk 104. A total of 92% (260/284) of the patients starting the third year of the trial completed the Wk 156 visit; overall, this is 52% (260/504) of patients randomized at baseline. Patients receiving APR30 at Wk 156 demonstrated sustained improvements, as shown by ACR20 response rates of 65%, swollen/tender joint count mean percent improvements of -81.2% and 73.2%, and HAQ-DI mean change of -0.37, and 41.9% of patients reaching DAS (CRP) <2.6. Similarly, the proportion of patients with HAQ-DI exceeding the minimal clinically important difference (MCID) ≥0.30 threshold, mean change in DAS-28 (CRP), and PASI-75/PASI-50 responses were maintained (Table). No new safety concerns were identified with up to 156 wks of APR treatment. During Wks >104 to ≤156 of APR exposure, the only adverse event (AE) occurring in ≥5% of patients was upper respiratory tract infection; most AEs were mild/moderate in severity. Serious AEs occurred in 6.9% (APR30) and 6.4% (APR20) of patients, similar to rates seen for the earlier study periods, few discontinuations due to AEs (0.7%) occurred over Wks >104 to ≤156.

Conclusions Over 156 wks, among patients remaining in the study, APR demonstrated sustained and clinically meaningful improvements in PsA signs/symptoms, including physical function and associated psoriasis. APR continued to demonstrate an acceptable safety profile and was generally well tolerated.

Acknowledgement We thank Adewale O. Adebajo for his work on the original abstract.

Disclosure of Interest A. Kavanaugh Grant/research support from: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB, D. Gladman Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer, Novartis, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer, Novartis, UCB, J. Gomez-Reino Grant/research support from: Roche, Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, UCB, Speakers bureau: Bristol-Myers Squibb, Roche, Schering-Plough, Wyeth, S. Hall Grant/research support from: Celgene Corporation, Pfizer, UCB, Bristol-Myers Squibb, Glaxo-Smith Kline, Roche, Janssen, Novartis, Merck, Consultant for: Celgene Corporation, Pfizer, UCB, Bristol-Myers Squibb, Glaxo-Smith Kline, Roche, Janssen, Novartis, Merck, E. Lespessailles Grant/research support from: Amgen, Eli Lilly, Novartis, Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, Servier, P. Mease Grant/research support from: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer, Celgene Corporation, Novartis, Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer, Celgene Corporation, Novartis, Roche, Speakers bureau: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer, G. Schett Grant/research support from: Abbott, Celgene Corporation, Roche, UCB, Consultant for: Abbott, Celgene Corporation, Roche, UCB, M. McIlraith Employee of: Celgene Corporation, K. Shah Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, J. Wollenhaupt Grant/research support from: Abbott, Bristol-Myers Squibb, MSD, Pfizer, UCB, Consultant for: Abbott, Bristol-Myers Squibb, MSD, Pfizer, UCB

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