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Repeat rituximab superior to azathioprine for preventing relapse in ANCA-associated vasculitis
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ATLANTA — Treatment with repeat doses of rituximab is superior to daily azathioprine for preventing relapse among patients with ANCA-associated vasculitis with a history of relapse, according to data presented at the 2019 ACR/ARP Annual Meeting.
“Rituximab is an effective remission induction agent in ANCA-associated vasculitis, and indeed in one of the pivotal remission induction trials in this condition, the RAVE trial, rituximab was actually shown to be superior to cyclophosphamide in individuals with relapsing disease,” Rona Smith, MD, MA, MB BChir, of the University of Cambridge, in the United Kingdom, told attendees.
“There remained unanswered questions in terms of the best remission strategy using rituximab,” she added. “Firstly, what is the best strategy in a purely relapsing population, the patients with the greatest unmet need? With increased use of rituximab as a remission induction agent, what is the best maintenance strategy from rituximab induction?”
To compare the efficacy of repeat doses of rituximab (Rituxan, Genentech) to daily oral azathioprine in preventing relapse among patients with ANCA-associated vasculitis following induced remission, Smith and colleagues conducted the RITAZAREM trial. This international, multicenter, open-label, randomized, controlled study initially included 190 patients, who were recruited at time of relapse and received induction therapy with rituximab and glucocorticoids.
The 170 participants who achieved remission by month four were randomized to receive either 1,000 mg doses of rituximab every 4 months, for a total of five doses, or daily oral azathioprine, at doses of 2 mg/kg. The researchers followed all randomized participants for 36 months. The primary outcome was the time to disease relapse. Smith and colleagues analyzed the HR for relapse throughout all time periods, with the HRs during the treatment and follow-up periods considered separately only if the global test was significant at a 5% level.
According to the researchers, rituximab was superior to azathioprine for preventing relapse, with a preliminary, overall estimated HR of 0.36 (95% CI, 0.23-0.57) and a during-treatment HR of 0.3 (95% CI, 0.15-0.6). None of the randomization stratification covariates, including ANCA type, glucocorticoid induction regimen or relapse severity, had a significant impact on the primary outcome following adjustments.
Data were complete for all randomized participants up to at least month 24. By that time, 20 months following randomization, 13% of patients in the rituximab group experienced relapse, compared with 38% of those in the azathioprine group. Among cases of relapse, 18% of those in the rituximab group were classified as major, compared with 38% of relapse cases in the azathioprine group.
In addition, 22% of patients in the rituximab group demonstrated at least one severe adverse event, compared with 36% of those treated with azathioprine. A total of 29% of participants who received repeated rituximab developed hypogammaglobulinaemia, while 49% experienced nonsevere infections. Among patients treated with azathioprine, 25% developed hypogammaglobulinaemia and 48% demonstrated nonsevere infections.
“Rituximab was superior to azathioprine for preventing disease relapse in patients with relapsing ANCA-associated vasculitis following re-induction of remission with rituximab,” Smith said. “In addition, there were no new major safety signals identified.” – by Jason Laday
Reference:
Smith R. Abstract #806. A randomized, controlled trial of rituximab versus azathioprine after induction of remission with rituximab for patients with ANCA-associated vasculitis and relapsing disease. Presented at: American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting; Nov. 9-13, 2019; Atlanta.
Disclosure: Smith reports professional relationships with Roche, Sanofi and Medimmune.