Rituximab Versus Conventional Therapy for Remission Induction in Eosinophilic Granulomatosis With Polyangiitis : A Randomized Controlled Trial

Abstract

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophilic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Rituximab has emerged as the standard of care in other types of ANCA-associated vasculitis, but controlled studies on its use in EGPA are yet lacking.

Objective: To compare rituximab with conventional strategy for the induction of remission in patients with EGPA.

Design: Phase 3, multicenter, randomized, controlled, double-blind, superiority trial. (ClinicalTrials.gov: NCT02807103).

Setting: France.

Participants: Patients with a diagnosis of EGPA, newly diagnosed or relapsing disease at the time of screening, with active disease defined as a Birmingham Vasculitis Activity Score (BVAS) of 3 or greater.

Intervention: Glucocorticoids plus rituximab (1 g 2 weeks apart) compared with the conventional strategy (glucocorticoids alone or in combination with cyclophosphamide in severe forms) for induction of remission.

Measurements: The primary end point was remission defined as a BVAS, version 3, of 0 and a prednisone dose of 7.5 mg/d or less at day 180. Secondary end points included duration of remission during the study, average daily glucocorticoid dose, and safety.

Results: A total of 105 participants were randomly assigned. Thirty-three (63.5%) patients in the rituximab group achieved the primary end point compared with 32 (60.4%) in the control group (relative risk, 1.05 [95% CI, 0.78 to 1.42]; P = 0.75). Results were similar at day 360. The mean duration of remission was 48.5 ± 6.51 weeks in the rituximab group and 49.1 ± 7.42 weeks in the conventional strategy group (P = 0.41). All relapse and major relapse rates were similar between the 2 groups. There was no statistically significant difference in the average daily glucocorticoid dose and no statistically significant differences in the rates of adverse events between the treatment groups.

Limitation: Design not appropriate to answer the question of equivalence between rituximab and cyclophosphamide in patients with severe EGPA.

Conclusions: Rituximab was not superior to a conventional remission induction strategy in EGPA.

Primary funding source: French Ministry of Health.