Adding low-dose cyclosphosphamide to rituximab is safe and prolongs relapse-free survival in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, recent study findings suggest.

A team led by Pieter van Paassen, MD, PhD, of Maastricht University Medical Center, and colleagues compared the use of rituximab alone with rituximab plus cyclosphosphamide for inducing remission. The median follow-up was 48 months (minimum follow-up of 2 years). At baseline, renal involvement was more common in the combination therapy arm than in the monotherapy arm (85% vs 61%), the investigators reported in the Journal of Translational Autoimmunity.

Major relapse rates within 2 years, but not after 5 years, were significantly lower in the rituximab-cyclosphosphamide arm than in the rituximab-only group (3% vs 24%). At 2 and 5 years, the groups did not differ with respect to rates of infection, end-stage kidney disease, malignancies, hypogammaglobulinemia, and mortality.

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“The results may support clinical decision making and contribute to future research,” the authors concluded. 

A major strength of the study is that it provides insight into treatment outcomes over a relatively long time period, with all patients followed up for at least 2 years, Dr van Paassen and colleagues noted. They also acknowledged study limitations, including a sample size that was “too small to create a prediction model and to identify possible risk factors for relapse and other adverse events.” Further, they pointed out that more patients in the combination arm than in the rituximab-only arm had renal involvement, “and clinicians tend to give [cyclosphosphamide] more frequently in patients with severe or rapidly progressive disease presentations.”


Ysermans R, Busch MH, Aendekerk JP, Damoiseaux JGMC, van Paassen P. Adding low dose cyclophosphamide to rituximab for remission-induction may prolong relapse-free survival in patients with ANCA vasculitis: A retrospective study. J Transl Autoimmun. 2022;6:100178. doi:10.1016/j.jtauto.2022.100178