Rituximab Superior to Azathioprine in Prevention of Relapse in ANCA-Associated Vasculitis

Repeat-dose rituximab was found to be superior to daily azathioprine in preventing relapse in patients with a prior history of relapse of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) following induction of rituximab, according to study findings published in Annals of the Rheumatic Diseases.

Researchers conducted an international, open-label, unblinded, randomized, controlled trial (ClinicalTrials.gov Identifier: NCT01697267) to compare the effectiveness of fixed-interval rituximab vs azathioprine in preventing relapse in patients with relapsing AAV who previously received rituximab and glucocorticoids.

The trial included 3 phases, including induction phase (enrollment through month 4), maintenance phase (4-24 months from enrollment), and follow-up phase (36-48 months from enrollment). 

Remission was defined using a Birmingham Vasculitis Activity Score for Wegener’s granulomatosis of 1 or lesser and prednisone/prednisolone dose of 10 mg/day or lesser. Patients who achieved disease remission by month 4 were randomly selected and assigned to receive rituximab or azathioprine for the maintenance phase.

The dosing for intravenous rituximab was 1000 mg that was repeated every 4 months for 5 doses (at months 4, 8, 12, 16, and 20 from enrollment) and the dosing for oral azathioprine was at 2 mg/kg/day for 24 months, which was decreased by 50% and withdrawn at month 27.

Eligible patients received treatment with prednisone/prednisolone at a dose of 10 mg/day or lesser at month 4, with the dose lowered to 5 mg/day from months 6 to 16 and further decreased to 2.5 mg/day at month 20 before being completely withdrawn.

The primary study outcome was time to disease relapse, which included both severe and nonsevere relapses.

A total of 170 patients were randomly assigned at month 4 to receive rituximab (n=85) or azathioprine (n=85). 

In the maintenance and follow-up phases, rituximab was superior to azathioprine in preventing both major and minor disease relapses (hazard ratio [HR], 0.41; 95% CI, 0.27-0.61; P <.001). Overall, 45% and 71% of patients in the rituximab and azathioprine groups, respectively, experienced relapse.

Researchers did not observe a significant difference in the length of time to the first serious adverse event to occur between the 2 groups. During the treatment period, 22% and 36% of patients in the rituximab and azathioprine groups, respectively, experienced at least 1 serious adverse event. There were also no significant differences in hypogammaglobulinaemia between the 2 groups.

Researchers concluded, “[R]epeat-dose rituximab is more effective than azathioprine for prevention of relapse for patients with AAV with relapsing disease induced with rituximab and glucocorticoids.”

They added, “Future treatment strategies for AAV may necessitate a more [individualized] approach, taking into account the risk of relapse balanced against the risk of adverse events with extended treatment.”