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Rituximab vs Azathioprine for Eosinophilic Granulomatosis With Polyangiitis Maintenance Therapy: A Randomized
Xavier Puéchal1,2, Grégory Pugnet3,4, Benjamin Thoreau5
1National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
Importance:
For patients with eosinophilic granulomatosis with polyangiitis (EGPA), guidelines recommend considering maintenance therapy after achieving remission. Data comparing maintenance therapeutic options are limited.
Objective:
To compare the effects of rituximab and azathioprine maintenance therapies on remission duration for patients with EGPA who recently achieved remission of vasculitis after standard therapy, including prednisone tapering or withdrawal.
Design, Setting, And Participants:
From March 7, 2018, to June 2, 2022, this double-blind, double-dummy, investigator-initiated, superiority, randomized clinical trial enrolled 98 participants with EGPA from 36 hospitals in France. Inclusion eligibility required a new EGPA diagnosis or relapsing EGPA within 30 to 360 days of achieving vasculitis remission (Birmingham Vasculitis Activity Score of 0 [range, 0-63, with higher scores indicating more severe disease activity]) after a standard induction regimen. Data were analyzed from April 1, 2025, to September 17, 2025. Additional analyses ended June 22, 2026.
Interventions:
Participants were randomized to receive a predefined standardized tapering of oral prednisone and either 500 mg of intravenous rituximab every 6 months for 18 months and daily oral azathioprine placebo for 24 months (n = 49) or rituximab placebo every 6 months for 18 months and daily oral azathioprine for 24 months (n = 49).
Main Outcomes And Measures:
The primary efficacy end point was the duration of total remission during the 28-month study period while taking 7.5 mg/d or less of prednisone. The 14 secondary end points included proportion of participants remaining in remission, rate of vasculitis relapse, and rate of asthma or rhinosinusitis exacerbations.
Results:
All 98 randomized participants (mean age, 59.0 years [SD, 14.4]; 50 women [51%]) received at least 1 dose of the trial regimen and 92 (94%) completed the trial. The mean time in remission with prednisone at 7.5 mg/d or less was 91.1 weeks (95% CI, 80.9-101.2) vs 96.0 weeks (95% CI, 85.6-106.5) in the rituximab and azathioprine groups, respectively (P = .38). The proportion of participants who remained in remission during the 28-month study period with prednisone at 7.5 mg/d or less was 17 of 49 (34.7%) vs 11 of 49 (22.4%; relative risk, 1.51; 95% CI, 0.83-2.73; P = .18) in the rituximab and azathioprine groups, respectively. The proportion of participants with at least 1 vasculitis relapse was 7 (14.3%) vs 9 (18.4%) in the rituximab vs azathioprine groups, respectively, and for those with at least 1 clinically significant asthma exacerbation, rhinosinusitis exacerbation, or both, it was 16 (32.7%) vs 19 (38.8%). One participant in the azathioprine group died of SARS-CoV-2 infection before vaccine development. Rituximab recipients experienced a higher incidence of severe infections (23 [46.9%] vs 12 [24.5%], respectively), primarily due to severe SARS-CoV-2 infections.
Conclusions And Relevance:
For participants with newly diagnosed or relapsing EGPA, rituximab was not superior to azathioprine for improving the duration of total remission during 28 months while taking prednisone at 7.5 mg/d or less.
Trial Registration:
ClinicalTrials.gov Identifier: NCT03164473.
