RITUXIMAB VERSUS CONVENTIONAL THERAPEUTIC STRATEGY FOR REMISSION INDUCTION IN EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS: A DOUBLE-BLIND, RANDOMIZED, CONTROLLED TRIAL
Authors: Benjamin Terrier et al.
Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophilic ANCA-associated vasculitis. Glucocorticoids, alone or in combination with cyclophosphamide, induce remission in in severe forms of EGPA. In contrast to the other ANCA-associated vasculitides, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the role of rituximab in EGPA is far from clear.
This phase 3, comparative, multicenter, randomized, controlled, double-blind and superiority trial compared rituximab-based regimen with conventional therapeutic strategies for the induction of remission. Patients with newly diagnosed or relapsing disease were randomized in a 1:1 ratio to receive rituximab or the conventional treatment based on Five-Factor Score (FFS)-assessed disease severity. The primary end point was the rate of patients who achieved remission at day 180 as defined by BVAS=0 and a prednisone dose ≤7.5 mg/day. Secondary end points were duration of remission during the study period, the average daily glucocorticoid dose and safety.
Of 105 participants (74 with newly diagnosed EGPA, 63 with FFS=0, 59 with negative ANCA), 52 received rituximab and 53 conventional treatment. At day 180, remission was achieved in 33 patients in the rituximab group (63.5%) and in 32 patients in the conventional strategy group (60.4%) (relative risk, 1.05; 95% confidence interval, 0.78 to 1.42, P=0.75). At day 360, remission was achieved in 31 patients in the rituximab group (59.6%) and in 34 patients in the conventional strategy group (64.2%) (relative risk, 1.08; 95% CI, 0.80 to 1.45, P=0.63). Mean duration of remission was 16.4 (10.37) and 16.2 (11.68) weeks in rituximab and conventional treatment, respectively. All relapse and major relapse rates were comparable between the two groups. SF-36 was similar between the two groups. However, health assessment questionnaire (HAQ) at day 180 and day 360 (p=0.07 and p=0.09, respectively) and vasculitis damage index (VDI) at day 360 (p=0.07) tended to be better in the rituximab group. There was no significant difference in average daily glucocorticoid dose between the two arms.
We tend to favor new drugs based on high-quality studies but also on marketing. This French study demonstrates an equality of rituximab and cyclophosphamide in the induction of remission of the rare EGPA. The treatment decisions were based on the FFS score, a score predicting outcome. The data give us a new basis for treatment decisions, they provide a choice in the induction strategy.