Prolonged rituximab linked to lower ANCA-associated vasculitis relapse
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A biannual regimen of rituximab infusions over the course of 18 months was associated with a lower incidence of relapse in ANCA-associated vasculitis, compared with standard maintenance therapy, according to data published in the Annals of Internal Medicine.
“Prolonged therapy with azathioprine was once recommended to maintain AAV remission, because a randomized trial showed lower relapse rates with long-term azathioprine therapy compared with the standard-length regimen,” Pierre Charles, MD, of Cochin Hospital, Paris Descartes University, in France, and colleagues wrote. “In 2014, the MAINRITSAN (Maintenance of Remission Using Rituximab in Systemic ANCA-Associated Vasculitis) trial reported the clear superiority of rituximab over azathioprine in maintaining remission, which influenced AAV treatment guidelines.”
“The therapeutic schedule of 500 mg of rituximab infused on days 0 and 14, then at months 6, 12 and 18, is now recommended by the U.S. Food and Drug Administration and European Medicines Agency to maintain AAV remission,” they added. “However, the MAINRITSAN trial showed that relapses after discontinuation of rituximab treatment were frequent, with a 57.9% relapse-free survival rate 32 months after the last rituximab infusion.”
To analyze the efficacy of prolonged rituximab (Rituxan, Genentech) in preventing relapse among patients with ANCA-associated vasculitis who had achieved remission after an 18-month maintenance regimen, Charles and colleagues conducted the randomized, controlled MAINRITSAN3 trial. Participants included 68 patients with granulomatosis with polyangiitis (GPA) and 29 with microscopic polyangiitis (MPA), recruited from a total of 39 centers in France. All participants had achieved complete remission following an 18-month maintenance regimen.
Researchers randomly assigned 50 patients to receive rituximab infusion and 47 placebo, every 6 months for 18 months, from March 2015 to April 2016. The primary endpoint was relapse-free survival at 28 months. The researchers defined relapse as new or reappearing symptoms, or worsening status, with a Birmingham Vasculitis Activity Score greater than 0.
According to the researchers, relapse-free survival estimates at month 28 were 96% among participants treated with rituximab (95% CI, 91% to 100%) and 74% in the placebo group (95% CI, 63% to 88%), representing an absolute difference of 22% (95% CI, 9% to 36%) and a hazard ratio of 7.5 (95% CI, 1.67-33.7).
Further, major relapse–free survival estimates at month 28 were 100% in the rituximab group (95% CI, 93% to 100%), compared with 87% among those who received a placebo (95% CI, 78% to 97%). At least 24% of patients in the rituximab group developed one serious adverse event, compared with 30% of those in the placebo group. No deaths were reported in either group.
“Our results demonstrated that prolonging rituximab treatment — that is, with 500 mg infused every 6 months for an additional 18 months after an initial 18-month maintenance regimen — was effective in sustaining remission, with relapse occurring in only two of 50 patients (4% [95% CI, 0% to 9%]) in the rituximab group versus 12 of 47 (26% [95% CI, 12% to 37%]) in the placebo group during the 28-month follow-up,” Charles and colleagues wrote. “No deaths occurred in either group. Long-term rituximab maintenance therapy did not seem to increase the number of adverse events or their severity.”
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