Rituximab Fails to Outperform Azathioprine in Preventing EGPA Relapses, Clinical Trial Finds
France: A randomized clinical trial published in JAMA found that rituximab was not superior to azathioprine for maintaining remission in patients with eosinophilic granulomatosis with polyangiitis (EGPA). The study showed no statistically significant difference between the treatments in the duration of remission among patients receiving low-dose prednisone, suggesting that rituximab may not offer an additional benefit over azathioprine for maintenance therapy.
EGPA is a rare inflammatory disease characterised by blood vessel inflammation, elevated eosinophils, and involvement of multiple organs, commonly affecting the respiratory tract. Treatment typically involves inducing remission with immunosuppressive therapy and subsequently maintaining disease control to prevent relapses. However, evidence directly comparing available maintenance treatments remains limited.
To address this gap, Xavier Puéchal from the National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, Assistance Publique–Hôpitaux de Paris, France, and colleagues conducted an investigator-initiated, double-blind, randomized clinical trial across 36 hospitals in France between March 2018 and June 2022.
The trial enrolled 98 patients who had achieved remission following standard treatment after a new EGPA diagnosis or a recent vasculitis relapse. Participants were randomly assigned to receive either intravenous rituximab every six months for 18 months or daily oral azathioprine for 24 months. Both groups followed a standardised prednisone tapering regimen.
The primary outcome was the total duration of remission over 28 months while patients were taking prednisone at a dose of 7.5 mg per day or less.
The findings revealed the following:
- No significant difference in remission duration: Patients receiving rituximab remained in remission for a mean of 91.1 weeks, compared with 96.0 weeks among those receiving azathioprine. The difference was not statistically significant (P = 0.38).
- Remission maintenance rates: At the end of the study period, 34.7% of rituximab recipients and 22.4% of azathioprine recipients remained in remission while taking low-dose prednisone. However, the difference did not reach statistical significance.
- Vasculitis relapses: At least one relapse occurred in 14.3% of patients receiving rituximab and 18.4% of those receiving azathioprine.
- Respiratory exacerbations: Clinically significant asthma or rhinosinusitis exacerbations occurred in 32.7% of the rituximab group and 38.8% of the azathioprine group.
- Severe infections: These were more frequent with rituximab, affecting 46.9% of participants, compared with 24.5% receiving azathioprine. Severe SARS-CoV-2 infections contributed substantially to this difference.
Overall, 92 of the 98 participants completed the trial. One participant in the azathioprine group died from SARS-CoV-2 infection.
The researchers concluded that rituximab did not provide a statistically significant advantage over azathioprine in maintaining EGPA remission over 28 months. The findings support considering both treatments in clinical decision-making while accounting for individual patient characteristics and safety concerns.
However, the relatively small sample size limits the precision of comparisons between treatments. Further research may help identify patient subgroups that benefit more from specific maintenance strategies.
Reference:
Puéchal X, Pugnet G, Thoreau B, et al. Rituximab vs Azathioprine for Eosinophilic Granulomatosis With Polyangiitis Maintenance Therapy: A Randomized Clinical Trial. JAMA. Published online October 22, 2026. doi:10.1001/jama.2026.15278
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