Rituximab should be the gold-standard treatment.
Pierre Charles, MD
Findings of a new analysis suggest extended therapy with biannual rituximab infusions over 18 months is associated with a lower incidence of antibody-associated vasculitis relapse compared with standard maintenance therapy.
Pierre Charles, MD, and a team of investigators evaluated the efficacy of prolonged rituximab therapy in preventing antibody-associated vasculitis relapse in patients with granulomatosis with polyangiitis or microscopic polyangiitis who achieved remission after an 18-month regimen. The multicenter, double-blind, randomized controlled trial randomly assigned patients to either receive prolonged maintenance therapy with 500 mg rituximab infusions biannually over 18 months (4 infusions) or placebo.
To be included in the trial, MAINRITSAN3, patients needed to successfully complete MAINRITSAN2 without any major relapses and be in complete remission. MAINRITSAN2 compared 2 rituximab infusion strategies for maintaining remission in patients with antibody-associated vasculitis.
Participants were recruited from 39 French centers. To be included, they had to have granulomatosis with polyangiitis or microscopic polyangiitis and be in complete remission at the time of rerandomization. Remission was defined as a Birmingham Vasculitis Activity Score of 0.
Charles and the team randomly assigned patients in a 1:1 ratio to receive the rituximab maintenance therapy or placebo. After randomization, patients either received an intravenous 500 mg fixed dose of rituximab or placebo at baseline, and at 6, 12, and 18 months.
The primary outcome of the study was a relapse-free survival 28 months after randomization. Additional endpoints included damage evaluated with the Vasculitis Damage Index and health-related quality of life.
Overall, 140 patients were eligible for rerandomization in MAINRITSAN3 and 97 were randomly assigned placebo or intervention. Of those assigned, 70% had granulomatosis with polyangiitis and 30% had microscopic polyangiitis. Among those, 52% of all patients were assigned to receive rituximab and 48% received placebo. Only 42 of the 50 patients who received rituximab had all the infusions, while 8 discontinued treatment. Ten patients stopped their treatment with placebo.
In the rituximab group, the relapse-free survival rate at 28 months was 96% (95% CI, 91-100) compared to 74% in the placebo group (95% CI, 63-88). The absolute difference was 22% (CI, 9-36) and the HR was 7.5 (95% CI, 1.67-33.7; P=.008). Relapse happened in 2 patients in the rituximab group.
At month 28, the major relapse-free survival estimates were 100% in the rituximab group (95% CI, 93-100) versus 87% in the placebo cohort (95% CI, 78-97) (P=.009).
There was >1 adverse event in patients in both groups. In the rituximab group, 24% of patients experienced at least 1 adverse event, while 30% of those in the placebo group did. There were no deaths recorded in either the placebo or rituximab group.
The findings of the study highlighted the need to use rituximab as the new gold standard to maintain remission of antibody-associated vasculitis, Charles and the team concluded. What’s more, the team found a sufficient dose per infusion (500 mg).
“On the basis of our results, we propose that future rituximab use be prolonged for patients at high risk for relapses, such as those with PR3 ANCAs and those who have already had a relapse,” the study authors wrote.
The study, “Long-Term Rituximab Use to Maintain Remission of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis,” was published online in Annals of Internal Medicine.