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SAT0382 Palace 4, A Phase 3, Randomized, Controlled TRIAL of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, for Treatment of Psoriatic Arthritis: Long-Term (52-WEEK) Improvements in Physical Function
  1. A. Wells1,
  2. C. Edwards2,
  3. A.O. Adebajo3,
  4. A.J. Kivitz4,
  5. P. Bird5,
  6. K. Shah6,
  7. C. Hu6,
  8. R.M. Stevens6,
  9. J.A. Aelion7
  1. 1Rheumatology and Immunotherapy Center, Franklin, United States
  2. 2University Hospital Southampton, Southampton
  3. 3University of Sheffield, Sheffield, United Kingdom
  4. 4Altoona Center for Clinical Research, Duncansville, United States
  5. 5Combined Rheumatology Practice, Kogarah, Australia
  6. 6Celgene Corporation, Summit
  7. 7West Tennessee Research Institute, Jackson, United States

Abstract

Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. PALACE 4 compared APR efficacy/safety with placebo (PBO) in patients (pts) with active PsA who were DMARD-naïve.

Objectives Evaluate the impact of APR over 52 wks on physical function among PALACE 4 pts.

Methods Pts were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30). Pts with <20% reduction from BL in SJC or TJC at Wk 16 were required to be re-randomized to APR20 or APR30 if initially randomized to PBO, or continued on the initial APR dose. At Wk 24, all remaining PBO pts were re-randomized to APR20 or APR30. This analysis reports data for Wks 0-52. Physical function was evaluated using HAQ-DI and SF-36v2 Physical Function (PF) domain and physical component summary (PCS) scores. Proportions of pts initially randomized to APR achieving minimum clinically important difference (MCID) thresholds at Wk 52 for HAQ-DI (≥0.13 or ≥0.30)1,2 and SF-36v2 PF and PCS (both ≥2.5)3 were determined.

Results At Wk 16, a significantly greater proportion of pts treated with APR achieved a modified ACR20 response vs PBO (primary endpoint). Mean changes in HAQ-DI at Wk 16 (key secondary endpoint) were 0.03 (PBO), -0.17 (APR20; P=0.0008), and -0.21 (APR30; P<0.0001). Among pts who were treated with APR continuously through 52 wks, sustained improvement in HAQ-DI was observed. Mean change in HAQ-DI was -0.32 (APR20) and -0.39 (APR30) at Wk 52, exceeding MCID thresholds of ≥0.13 or ≥0.30 (Table). At Wk 52, 56.8% (APR20) and 59.0% (APR30) achieved HAQ-DI MCID ≥-0.13 and 48.5% and 48.9% achieved MCID ≥-0.30, respectively. Wk 52 mean changes from BL in SF-36v2 PF (APR20, 4.61; APR30, 6.41) and PCS (APR20, 5.55; APR30, 6.67) exceeded the MCID threshold (≥2.5). At Wk 52, 57.6% of APR20 and APR30 pts achieved SF-36v2 PF MCID, and 60.6% (APR20) and 69.1% (APR30) achieved SF-36v2 PCS MCID. The most common AEs reported during the PBO-controlled period were nausea (12.6%), diarrhea (9.4%), and headache (6.0%). The safety profile of APR for up to 52 wks was similar to that observed with APR for up to 24 wks of treatment (PBO-controlled period).

Conclusions Over 52 wks, APR continued to demonstrate clinically meaningful improvements in physical function in active PsA pts who were DMARD-naive. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 wks.

References

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  2. Mease PJ. J Rheumatol. 2011;38:2461.

  3. Revicki DA. Health Qual Life Outcomes. 2008;6:75.

Disclosure of Interest A. Wells Grant/research support: Celgene Corporation, C. Edwards Grant/research support: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Consultant for: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, A. Adebajo: None declared, A. Kivitz Grant/research support: Amgen, Janssen, Eli Lilly, Novartis, Pfizer Inc, and UCB, Consultant for: Amgen, Janssen, Eli Lilly, Novartis, Pfizer Inc, and UCB, Speakers bureau: Pfizer Inc, P. Bird Grant/research support: Celgene Corporation, K. Shah Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, J. Aelion Grant/research support: Ardea, Astra Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor, Galapagos, Genentech, GlaxoSmithKline, Human Genome Sciences, Janssen, Eli Lilly, Merck, Mesoblast, Novartis, Novo Nordisk, Pfizer Inc, Roche, UCB Biosciences, Sanofi-Aventis, Takeda, and Vertex, Consultant for: Ardea, Astra Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor, Galapagos, Genentech, GlaxoSmithKline, Human Genome Sciences, Janssen, Eli Lilly, Merck, Mesoblast, Novartis, Novo Nordisk, Pfizer Inc, Roche, UCB Biosciences, Sanofi-Aventis, Takeda, and Vertex, Speakers bureau: AbbVie, Amgen, and UCB

DOI 10.1136/annrheumdis-2014-eular.1096

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