Glen S Hazlewood1, Claudia Metzler2, George A Tomlinson3, Wolfgang L Gross4, Brian M Feldman5, Loic Guillevin6, Christian Pagnoux7. 1. Department of Internal Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, Alberta, T2N1N1 Canada. Electronic address: glenhazlewood@gmail.com. 2. University of Lubeck, Bad Branstedy, Germany. 3. University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, ON, Canada. 4. Medical University at Lubeck, Lubeck, Germany. 5. The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, Canada. 6. Department of Internal Medicine, Cochin Hospital, Assistance publique-Hôpitaux de Paris, université Paris-Descartes, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France. 7. Mount Sinai Hospital, University of Toronto, 60 Murray Street, 2nd Floor, Room 222, Toronto, Ontario, Canada.
Abstract
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.
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.
Authors: Jan Henrik Schirmer; Peer M Aries; Kirsten de Groot; Bernhard Hellmich; Julia U Holle; Christian Kneitz; Ina Kötter; Peter Lamprecht; Ulf Müller-Ladner; Eva Reinhold-Keller; Christof Specker; Michael Zänker; Frank Moosig Journal: Z Rheumatol Date: 2017-11 Impact factor: 1.372
Authors: Lena W Chen; Ioan Lina; Kevin Motz; Alexandra J Berges; Rafael Ospino; Philip Seo; Alexander T Hillel Journal: Otolaryngol Head Neck Surg Date: 2021-04-13 Impact factor: 3.497