TY - JOUR
T1 - Non-biologic remission maintenance therapy in adult patients with ANCA-associated vasculitis: A systematic review and network meta-analysis
AU - Hazlewood, Glen S.
AU - Metzler, Claudia
AU - Tomlinson, George A.
AU - Gross, Wolfgang L.
AU - Feldman, Brian M.
AU - Guillevin, Loic
AU - Pagnoux, Christian
N1 - Funding Information:
G.H. has received grant support from UCB and honoraria from Abbott and UCB. C.M. has received travel fees from Aventis, Hoffmann–La Roche Ltd, and Glaxo-Smith-Kline and speaking fees from Hoffmann–La Roche Ltd. B.F. has received grant support from Baxter and Bayer and has served on a drug monitoring committee for BMS, Novartis and Pfizer. C.P. has received consulting fees and/or speaking fees from Hoffmann–La Roche Ltd. Several study authors were authors of the original trials reviewed (C.M., W.G., L.G., C.P.). The authors of the LEF-MTX trial who were involved with this study (C.M., W.G.) were not involved with the study concept, design or data analysis, but provided original data key to the study, reviewed, edited and approved the final manuscript.
Funding Information:
G.H. is supported by an Alberta Innovates Health Solutions Clinical Fellowship. C.P. received fellowship grants from the Vasculitis Clinical Research Consortium and the Toronto General Hospital/Toronto Western Hospital Foundation/University Health Network, Toronto, ON, Canada. Appendix A
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/7
Y1 - 2014/7
N2 - Objective: To determine the comparative efficacy of non-biologic treatments for remission maintenance in ANCA-associated vasculitis. Methods: We identified all randomized trials comparing leflunomide, azathioprine, methotrexate or mycophenolate mofetil in adult patients with granulomatosis with polyangiitis or microscopic polyangiitis. Relapse-free survival was compared through hazard ratios (HR) using a Bayesian fixed-effects network meta-analysis. Multiple sensitivity analyses were performed to explore biases identified in one trial using original trial data. Results: Three trials were available (leflunomide-methotrexate, methotrexate- azathioprine, azathioprine-mycophenolate). Mycophenolate was inferior to all treatments, although the 95% credible interval (CrI) of the HR relative to methotrexate crossed 1. Leflunomide was superior to azathioprine (HR 0.43 [95% CrI: 0.14-1.3]) and methotrexate (HR 0.47 [95% CrI: 0.18-1.2]), although the 95% CrI also crossed 1. There was a 90% probability that leflunomide was the best treatment. After down weighting the effect of leflunomide vs. methotrexate for early trial termination and slow MTX dose escalation, there remained a 55% probability leflunomide was best. Conclusion: Based on indirect evidence, leflunomide is effective in maintaining remission in granulomatosis with polyangiitis or microscopic polyangiitis relative to other non-biologic treatments. Further randomized trials of leflunomide are needed for confirmation.
AB - Objective: To determine the comparative efficacy of non-biologic treatments for remission maintenance in ANCA-associated vasculitis. Methods: We identified all randomized trials comparing leflunomide, azathioprine, methotrexate or mycophenolate mofetil in adult patients with granulomatosis with polyangiitis or microscopic polyangiitis. Relapse-free survival was compared through hazard ratios (HR) using a Bayesian fixed-effects network meta-analysis. Multiple sensitivity analyses were performed to explore biases identified in one trial using original trial data. Results: Three trials were available (leflunomide-methotrexate, methotrexate- azathioprine, azathioprine-mycophenolate). Mycophenolate was inferior to all treatments, although the 95% credible interval (CrI) of the HR relative to methotrexate crossed 1. Leflunomide was superior to azathioprine (HR 0.43 [95% CrI: 0.14-1.3]) and methotrexate (HR 0.47 [95% CrI: 0.18-1.2]), although the 95% CrI also crossed 1. There was a 90% probability that leflunomide was the best treatment. After down weighting the effect of leflunomide vs. methotrexate for early trial termination and slow MTX dose escalation, there remained a 55% probability leflunomide was best. Conclusion: Based on indirect evidence, leflunomide is effective in maintaining remission in granulomatosis with polyangiitis or microscopic polyangiitis relative to other non-biologic treatments. Further randomized trials of leflunomide are needed for confirmation.
UR - http://www.scopus.com/inward/record.url?scp=84904116116&partnerID=8YFLogxK
U2 - 10.1016/j.jbspin.2013.11.006
DO - 10.1016/j.jbspin.2013.11.006
M3 - Journal articles
C2 - 24387970
AN - SCOPUS:84904116116
SN - 1297-319X
VL - 81
SP - 337
EP - 341
JO - Joint Bone Spine
JF - Joint Bone Spine
IS - 4
ER -
