medwireNews: Long-term maintenance treatment with biannual rituximab infusions increases the likelihood of remaining in remission among people with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), suggest findings from the MAINRITSAN3 trial.
The phase 3 study included 97 patients – 68 with granulomatosis with polyangiitis and 29 with microscopic polyangiitis – who were in complete remission after receiving an 18-month rituximab maintenance regimen in MAINRITSAN2. Participants were randomly assigned to receive prolonged maintenance therapy with either intravenous rituximab (500 mg every 6 months) or placebo for a further 18 months in MAINRITSAN3, with all patients given premedication with methylprednisolone, dexchlorpheniramine, and acetaminophen before each infusion of a study drug.
As reported in the Annals of Internal Medicine, relapse-free survival rates at month 28 were significantly higher among the 50 patients given prolonged rituximab compared with the 47 given placebo, at 96% versus 74% (hazard ratio=7.5).
Participants in the rituximab group also had significantly higher rates of major relapse-free survival (100 vs 87%), but rates of minor relapse-free survival and measures of quality of life and vasculitis damage were not significantly different between the two groups.
The researchers note that “relapses seemed to occur more frequently in patients with AAV and PR3 [anti-proteinase-3] ANCA positivity than in those with MPO [myeloperoxidase] positivity.” For instance, in the placebo arm, 40% of 25 patients with PR3 ANCA positivity experienced a relapse, compared with just 12% of the 17 patients with MPO ANCA positivity.
In all, 92% of participants in the rituximab group and 94% of those given placebo experienced adverse events (AEs), with serious AEs reported in 24% and 30%, respectively, and serious infectious AEs occurring in a corresponding 12% and 9%. There were no deaths in either arm.
“Long-term rituximab maintenance therapy did not seem to increase the number of adverse events or their severity,” summarize Loïc Guillevin (Hôpital Cochin, Paris, France) and co-investigators.
Taking the findings of all three MAINRITSAN trials into account, the study authors conclude: “Rituximab should become the new gold standard to maintain remission, a 500-mg dose per infusion is sufficient, treatment should be prolonged, and an individually tailored regimen may be prescribed.
“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.”
Writing in an accompanying editorial, Gary Hoffman (Cleveland Clinic, Ohio, USA) says that “[t]he authors make a convincing argument that long-term rituximab should be the standard of care for ANCA-associated vasculitis.”
However, he cautions that “results must be viewed in the context of patient status at enrollment: Patients were in remission, did not require high-dose corticosteroids, and had tolerated rituximab well in MAINRITSAN2.”
And noting that “rituximab therapy was not without some serious adverse events,” he says: “[A]n unanswered question is, how long should long-term treatment continue in any patient?”
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