Objective To compare long-term efficacy of remission-maintenance regimens in patients with newly diagnosed or relapsing antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides.
Methods The 28-month Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis trial compared rituximab with azathioprine to maintain remission in patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis or renal-limited ANCA-associated vasculitis. Thereafter, prospective patient follow-up lasted until month 60. The primary endpoint was the major-relapse rate at month 60. Relapse and serious adverse event-free survival were also assessed.
Results Among the 115 enrolled patients, only one was lost to follow-up at month 60. For the azathioprine and rituximab groups, respectively, at month 60, the major relapse-free survival rates were 49.4% (95% CI 38.0% to 64.3%) and 71.9% (95% CI 61.2% to 84.6%) (p=0.003); minor and major relapse-free survival rates were 37.2% (95% CI 26.5% to 52.2%) and 57.9% (95% CI 46.4% to 72.2%) (p=0.012); overall survival rates were 93.0% (95% CI 86.7% to 99.9%) and 100% (p=0.045) and cumulative glucocorticoid use was comparable. Quality-adjusted time without symptoms and toxicity analysis showed that rituximab-treated patients had 12.6 months more without relapse or toxicity than those given azathioprine (p<0.001). Antiproteinase-3-ANCA positivity and azathioprine arm were independently associated with higher risk of relapse. HRs of positive ANCA to predict relapse increased over time.
Conclusion The rate of sustained remission for ANCA-associated vasculitis patients, following rituximab-based or azathioprine-based maintenance regimens, remained superior over 60 months with rituximab, with better overall survival.
Trial registration number NCT00748644.
- systemic vasculitis
- granulomatosis with polyangiitis
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Handling editor Josef S Smolen
Contributors BT, CP and LG contributed to data collection, data analysis and interpretation, manuscript preparation and review. EP and PR contributed to data analysis and interpretation, manuscript preparation and review. AK, CK, OA, PC, OD, HD-C, FM, PG, TQ, CB-D, BB, P-LC, ED, MD, PG, MH, OL, NL, XP and LM contributed to data generation, analysis and interpretation and manuscript preparation.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests BT has received lecture fees from Roche/Genentech and advisory board fees from ChemoCentryx. CP has received research grants and lecture fees from Roche/Genentech and advisory board fees from ChemoCentryx and Sano.
Patient consent Obtained
Ethics approval Local Institutional Review Board, CPP Paris Ile de France 3.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All study data are included in this manuscript.
Collaborators A complete list of additional investigators and members of the French Vasculitis Study Group. The authors’ full names and academic degrees are as follows: Florence Vendé, MD, Maxime Samson, MD, PhD, Pierre‑Yves Hatron, MD, PhD, Abdeldjallil Koreichi, MD, Alain Ramassamy, MD, Hélène Francois, MD, PhD, Ali Boumallassa, MD, Anne-Bérangère Beucher, MD, Aurélien Delluc, MD, PhD, Bruno Graffin, MD, Catherine Hanrotel-Saliou, MD, Claire Grange, MD, David Launay, MD, PhD, Denis Bagnères, MD, Edouard Begon, MD, Frédéric Grassin, MD, Frédérique Bocquentin, MD, Guillaume Gondran, MD, Isabelle Delacroix, MD, Isabelle Guichard, MD, Isabelle Marie, MD, PhD, Jaques Pourrat, MD, PhD, Jean-François Viallard, MD, PhD, Benoit Wallaert, MD, PhD, Laure Lahaxe, MD, Laurence Vrigneaud, MD, Marc Fabre, MD, Marie Frimat, MD, Marie Lino, MD, Martine Gayraud, MD, Matthias Buchler, MD, PhD, Myriam Niel-Duriez, MD, Nolwenn Rabot, MD, Raphaèle Seror, MD, Ph.D., Roderich Meckenstock, MD, Serge Perrot, MD, PhD, Serge Seiberras, MD, Robin Dhote, MD, PhD, Vincent Poindron, MD, Virginie Rieu, MD, Xavier Delbrel, MD, Xavier Kyndt, MD, Yann Ollivier, MD.