The efficacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythematosus: Results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial

Merrill, J. T., Burgos-Vargas, R., Westhovens, R., Chalmers, A., D'Cruz, D., Wallace, D. J., Bae, S. C., Sigal, L., Becker, J.-C., Kelly, S., Raghupathi, K., Li, T., Peng, Y., Kinaszczuk, M. and Nash, P. (2010) The efficacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythematosus: Results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial. Arthritis and Rheumatism, 62 10: 3077-3087. doi:10.1002/art.27601


Author Merrill, J. T.
Burgos-Vargas, R.
Westhovens, R.
Chalmers, A.
D'Cruz, D.
Wallace, D. J.
Bae, S. C.
Sigal, L.
Becker, J.-C.
Kelly, S.
Raghupathi, K.
Li, T.
Peng, Y.
Kinaszczuk, M.
Nash, P.
Title The efficacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythematosus: Results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial
Journal name Arthritis and Rheumatism   Check publisher's open access policy
ISSN 0004-3591
1529-0131
Publication date 2010-01-01
Sub-type Article (original research)
DOI 10.1002/art.27601
Open Access Status Not Open Access
Volume 62
Issue 10
Start page 3077
End page 3087
Total pages 11
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Subject 2403 Immunology
2723 Immunology and Allergy
2745 Rheumatology
2736 Pharmacology (medical)
Formatted abstract
Objective: To evaluate abatacept therapy in patients with non-life-threatening systemic lupus erythematosus (SLE) and polyarthritis, discoid lesions, or pleuritis and/or pericarditis.

Methods: In a 12-month, multicenter, exploratory, phase IIb randomized, double-blind, placebo-controlled trial, SLE patients with polyarthritis, discoid lesions, or pleuritis and/or pericarditis were randomized at a ratio of 2:1 to receive abatacept (∼10 mg/kg of body weight) or placebo. Prednisone (30 mg/day or equivalent) was given for 1 month, and then the dosage was tapered. The primary end point was the proportion of patients with new flare (adjudicated) according to a score of A/B on the British Isles Lupus Assessment Group (BILAG) index after the start of the steroid taper.

Results: A total of 118 patients were randomized to receive abatacept and 57 to receive placebo. The baseline characteristics were similar in the 2 groups. The proportion of new BILAG A/B flares over 12 months was 79.7% (95% confidence interval [95% CI] 72.4, 86.9) in the abatacept group and 82.5% (95% CI 72.6, 92.3) in the placebo group (treatment difference -3.5 [95% CI -15.3, 8.3]). Other prespecified flare end points were not met. In post hoc analyses, the proportions of abatacept-treated and placebo-treated patients with a BILAG A flare were 40.7% (95% CI 31.8, 49.5) versus 54.4% (95% CI 41.5, 67.3), and the proportions with physician-assessed flare were 63.6% (95% CI 54.9, 72.2) and 82.5% (95% CI 72.6, 92.3), respectively; treatment differences were greatest in the polyarthritis group. Prespecified exploratory patient-reported outcomes (Short Form 36 health survey, sleep problems, fatigue) demonstrated a treatment effect with abatacept. The frequency of adverse events (AEs) was comparable in the abatacept and placebo groups (90.9% versus 91.5%), but serious AEs (SAEs) were higher in the abatacept group (19.8 versus 6.8%). Most SAEs were single, disease-related events occurring during the first 6 months of the study (including the steroid taper period).

Conclusion: Although the primary/secondary end points were not met in this study, improvements in certain exploratory measures suggest some abatacept efficacy in patients with non-life-threatening manifestations of SLE. The increased rate of SAEs requires further assessment. 
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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