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AB0746 Apremilast, an Oral Phosphodiesterase 4 Inhibitor, and the Impact of Baseline Weight and BMI on ACR20 and HAQ-DI Response: Pooled Results from 3 Phase 3, Randomized, Controlled Trials
  1. G. Schett1,
  2. P. Mease2,
  3. D. Gladman3,
  4. A. Kavanaugh4,
  5. A. Adebajo5,
  6. J. Gomez-Reino6,
  7. J. Wollenhaupt7,
  8. M. Cutolo8,
  9. E. Lespessailles9,
  10. C. Hu10,
  11. R. Stevens10,
  12. C. Edwards11,
  13. C. Birbara12
  1. 1University Erlangen-Nuremberg, Erlangen, Germany
  2. 2Swedish Medical Center and University of Washington School of Medicine, Seattle, United States
  3. 3Toronto Western Hospital, Toronto, Canada
  4. 4University of California San Diego, San Diego, United States
  5. 5University of Sheffield, Sheffield, United Kingdom
  6. 6Hospital Clinico Universitario, Santiago, Spain
  7. 7Schön Klinik Hamburg Eilbek, Hamburg, Germany
  8. 8University of Genova, Genova, Italy
  9. 9University of Orléans, Orléans, France
  10. 10Celgene Corporation, Warren, United States
  11. 11University Hospital Southampton, Southampton, United Kingdom
  12. 12University of Massachusetts Medical School, Worcester, United States

Abstract

Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. PALACE 1, 2, and 3 compared the efficacy and safety of APR with placebo (PBO) in patients with active psoriatic arthritis (PsA) despite prior disease-modifying antirheumatic drugs and/or biologics.

Objectives Assess the impact of baseline weight and body mass index (BMI) on clinical response to APR over 24 weeks in a pooled analysis.

Methods Patients were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). Patients with <20% reduction from baseline in swollen or tender joint counts at Week 16 were required to be re-randomized to APR20 or APR30 if initially randomized to PBO, or continued on their initial APR dose. At Week 24, all remaining PBO patients were re-randomized to APR20 or APR30.

Results 1493 patients were randomized, received ≥1 dose of study medication (PBO: n=496; APR20: n=500; APR30: n=497), and were comparable across treatment groups for demographics, disease characteristics, and prior/concurrent therapy. At baseline, mean (SD) weight was 85.7 (20.6) kg and mean (SD) BMI was 29.9 (6.5) kg/m2. APR administration resulted in statistically significant and clinically meaningful improvement in ACR20 response (primary endpoint) in all 3 PALACE trials. APR30 was associated with significant improvements in Health Assessment Questionnaire-Disability Index (HAQ-DI) vs PBO at Week 16 (key secondary endpoint) across all 3 trials. At Week 16, similar ACR20 response rates and improvements in HAQ-DI were observed across all weight and BMI ranges (Table). A favorable treatment effect for both APR treatment groups vs PBO was observed, irrespective of baseline body weight or BMI. Overall, the treatment effect was dose-dependent, with greater effects generally observed in APR30 over APR20 patients. These treatment effects were generally maintained at Week 24.

Conclusions APR demonstrated a favorable treatment effect in patients with active PsA. Comparable improvements in the signs and symptoms of PsA and physical function were observed across a broad range of baseline weight and BMI values. Results suggest no dose adjustment is required to account for baseline body weight or BMI.

Disclosure of Interest G. Schett Grant/research support: Abbott, Celgene Corporation, Roche, P. Mease Grant/research support: Celgene Corporation, Novartis, and Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB, D. Gladman Grant/research support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, A. Kavanaugh Consultant for: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/research support: Bristol-Myers Squibb, Roche, Schering-Plough, and Wyeth; and has received research grants from Roche and Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, and UCB SA, J. Wollenhaupt Grant/research support: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, M. Cutolo Grant/research support: Actelion, Bristol-Myers Squibb, and, E. Lespessailles Grant/research support: Amgen, Eli Lilly, Novartis, and Servier, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/research support: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, C. Birbara Grant/research support: Amgen, Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and

DOI 10.1136/annrheumdis-2014-eular.1773

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