TY - JOUR
T1 - A network meta-analysis of randomized controlled trials of biologics for rheumatoid arthritis
T2 - A Cochrane overview
AU - Singh, Jasvinder A.
AU - Christensen, Robin
AU - Wells, George A.
AU - Suarez-Almazor, Maria E.
AU - Buchbinder, Rachelle
AU - Lopez-Olivo, Maria Angeles
AU - Ghogomu, Elizabeth Tanjong
AU - Tugwell, Peter
N1 - Funding Information:
Funding: Jasvinder Singh is supported by a US National Institutes of Health Center for Clinical and Translational Science Award (no. 1 KL2 RR024151-01). Robin Christensen is supported by the Parker Institute, Musculoskeletal Statistics Unit, and the Oak Foundation, Switzerland. Rachelle Buchbinder is partially supported by an Australian National Health and Medical Research Council Practitioner Fellowship.
Funding Information:
Competing interests: Jasvinder Singh has received speaker fees from Abbott, research and travel grants from Takeda, Savient, Wyeth and Amgen and consultant fees from Savient and URL Pharma. Robin Christensen and George Wells have received research grants and consultant fee from Bristol-Myers Squibb and Abbott. Maria Suarez-Almazor has received speaker fees from Bristol-Myers Squibb and Roche and consultant fees from Amgen. Rachelle Buchbinder is chief investigator of the Australian Rheumatology Association Database (ARAD), which is funded by an enabling grant from the Australian National Health and Medical Research Council and by Monash University. The Australian Rheumatology Association currently receives educational grants from Abbott Australasia Pty Ltd, Roche Products Pty Ltd and Wyeth Australia Pty Ltd and has previously received educational grants from Amgen Australia Pty Ltd, Aventis and Schering Plough in support of ARAD. Peter Tugwell has received consultant fees from Bristol Myers, Chiltern International and UCB Pharmaceuticals. No competing interests declared by Maria Angeles Lopez-Olivo or Elizabeth Tanjong Ghogomu.
PY - 2009/11/24
Y1 - 2009/11/24
N2 - Background: We sought to compare the benefits and safety of 6 biologics (abatacept, adalimumab, anakinra, etanercept, infliximab and rituximab) in patients with rheu matoid arthritis. Methods: In this network meta-analysis, we included all completed and updated Cochrane reviews on biologics for rheumatoid arthritis. We included data from all placebocontrolled trials that used standard dosing regimens. The major outcomes were benefit (defined as a 50% improvement in patient- and physician-reported criteria of the American College of Rheumatology [ACR50]) and safety (determined by the number of withdrawals related to adverse events). We used mixed-effects logistic regression to carry out an indirect comparison of the treatment effects between biologics. Results: Compared with placebo, biologics were associated with a clinically important higher ACR50 rate (odds ratio [OR] 3.35, 95% confidence interval [CI] 2.62-4.29) and a number needed to treat for benefit of 4 (95% CI 4-6). However, biologics were associated with more withdrawals related to adverse events (OR 1.39, 95% CI 1.13-1.71), with a number needed to treat for harm of 52 (95% CI 29-152). Anakinra was less effective than all of the other biologics, although this difference was statistically significant only for the comparison with adalimumab (OR 0.45, 95% CI 0.21-0.99) and etanercept (OR 0.34, 95% CI 0.14-0.81). Adalimumab, anakinra and infliximab were more likely than etanercept to lead to withdrawals related to adverse events (adalimumab OR 1.89, 95% CI 1.18-3.04; anakinra OR 2.05, 95% CI 1.27-3.29; and infliximab OR 2.70, 95% CI 1.43-5.26). Interpretation: Given the limitations of indirect comparisons, anakinra was less effective than adalimumab and etanercept, and etanercept was safer than adalimumab, anakinra and infliximab. This summary of the evidence will help physicians and patients to make evidence-based choices about biologics for the treatment of rheumatoid arthritis.
AB - Background: We sought to compare the benefits and safety of 6 biologics (abatacept, adalimumab, anakinra, etanercept, infliximab and rituximab) in patients with rheu matoid arthritis. Methods: In this network meta-analysis, we included all completed and updated Cochrane reviews on biologics for rheumatoid arthritis. We included data from all placebocontrolled trials that used standard dosing regimens. The major outcomes were benefit (defined as a 50% improvement in patient- and physician-reported criteria of the American College of Rheumatology [ACR50]) and safety (determined by the number of withdrawals related to adverse events). We used mixed-effects logistic regression to carry out an indirect comparison of the treatment effects between biologics. Results: Compared with placebo, biologics were associated with a clinically important higher ACR50 rate (odds ratio [OR] 3.35, 95% confidence interval [CI] 2.62-4.29) and a number needed to treat for benefit of 4 (95% CI 4-6). However, biologics were associated with more withdrawals related to adverse events (OR 1.39, 95% CI 1.13-1.71), with a number needed to treat for harm of 52 (95% CI 29-152). Anakinra was less effective than all of the other biologics, although this difference was statistically significant only for the comparison with adalimumab (OR 0.45, 95% CI 0.21-0.99) and etanercept (OR 0.34, 95% CI 0.14-0.81). Adalimumab, anakinra and infliximab were more likely than etanercept to lead to withdrawals related to adverse events (adalimumab OR 1.89, 95% CI 1.18-3.04; anakinra OR 2.05, 95% CI 1.27-3.29; and infliximab OR 2.70, 95% CI 1.43-5.26). Interpretation: Given the limitations of indirect comparisons, anakinra was less effective than adalimumab and etanercept, and etanercept was safer than adalimumab, anakinra and infliximab. This summary of the evidence will help physicians and patients to make evidence-based choices about biologics for the treatment of rheumatoid arthritis.
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U2 - 10.1503/cmaj.091391
DO - 10.1503/cmaj.091391
M3 - Article
C2 - 19884297
AN - SCOPUS:72949116165
SN - 0820-3946
VL - 181
SP - 787
EP - 796
JO - CMAJ
JF - CMAJ
IS - 11
ER -