Abatacept in the treatment of patients with psoriatic arthritis: results of a six-month, multicenter, randomized, double-blind, placebo-controlled, phase II trial.

Abstract

OBJECTIVE:

To assess the safety and efficacy of abatacept, a selective T cell costimulation modulator, in patients with psoriatic arthritis (PsA).

METHODS:

In this 6-month, multicenter, randomized, double-blind, placebo-controlled, phase II study, 170 PsA patients with a psoriasis target lesion (TL) ≥2 cm who had previously taken disease-modifying antirheumatic drugs (DMARDs), including anti-tumor necrosis factor (anti-TNF) agents, were randomized (1:1:1:1) to receive placebo or abatacept at doses of 3 mg/kg, 10 mg/kg, or 30/10 mg/kg (2 initial doses of 30 mg/kg, followed by 10 mg/kg) on days 1, 15, and 29 and then once every 28 days thereafter. The primary end point was the American College of Rheumatology 20% criteria for improvement (ACR20 response) on day 169. Other key end points were magnetic resonance imaging (MRI) scores for joint erosion, osteitis, and synovitis, scores on the Health Assessment Questionnaire (HAQ) and the Short Form-36 (SF-36) health survey, the investigator's global assessment of psoriasis, the TL score, and the Psoriasis Area and Severity Index (PASI) score.

RESULTS:

Proportions of patients achieving an ACR20 response were 19%, 33%, 48%, and 42% in the placebo, the abatacept 3 mg/kg, the abatacept 10 mg/kg, and the abatacept 30/10 mg/kg groups, respectively. Compared with placebo, improvements were significantly higher for the abatacept 10 mg/kg (P = 0.006) and 30/10 mg/kg (P = 0.022) groups, but not for 3 mg/kg group (P = 0.121). All abatacept regimens resulted in improved MRI, HAQ, and SF-36 scores, with 10 mg/kg showing the greatest improvements. Improvements in the TL and PASI scores were observed in all abatacept arms; a response according to the investigator's global assessment was seen only with 3 mg/kg of abatacept. The safety profiles were similar among the treatment arms.

CONCLUSION:

The results of this study suggest that 10 mg/kg of abatacept, the approved dosage for rheumatoid arthritis and juvenile idiopathic arthritis, may be an effective treatment option for PsA.

• Authors: Philip Mease, Mark C Genovese, Geoffrey Gladstein, Alan J Kivitz, Christopher Ritchlin, Paul P Tak, Jürgen Wollenhaupt, Orna Bahary, Jean-Claude Becker, Sheila Kelly, Leonard Sigal, Julie Teng, Dafna Gladman
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 63 Issue 4 Pg. 939-48 (Apr 2011) ISSN: 1529-0131 [Electronic] United States
• PMID: 21128258 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 by the American College of Rheumatology.

Chemical References

• Antirheumatic Agents
• Immunoconjugates
• Abatacept

Topics

• Abatacept
• Adult
• Antirheumatic Agents (adverse effects, pharmacology, therapeutic use)
• Arthritis, Psoriatic (drug therapy, pathology)
• CD4-Positive T-Lymphocytes (drug effects, pathology)
• CD8-Positive T-Lymphocytes (drug effects, pathology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Immunoconjugates (adverse effects, pharmacology, therapeutic use)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Outcome Assessment, Health Care
• Quality of Life
• Severity of Illness Index
• Treatment Outcome