At least 2 years of maintenance rituximab remains ‘reasonable option’ for ANCA vasculitis
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Treatment with a fixed interval of either 500 mg or 1,000 mg rituximab for at least 2 years is a “reasonable option” for patients with anti-neutrophil cytoplasmic autoantibody vasculitis upon achieving remission, according to a presenter here.
During her presentation at the Biologic Therapies Summit, Rona Smith, MD, senior research associate and honorary consultant in nephrology and vasculitis at Cambridge University Hospitals, raised questions about the optimal dose and duration of rituximab (Rituxan, Genentech) maintenance therapy in ANCA vasculitis. In addition, she discussed fixed versus individually tailored regimens for this patient population.
“To attempt to answer these questions, we need to look at the results of four trials,” Smith said, namely the three MAINRITSAN studies and the RITAZRAM study.
The first MAINRITSAN study included 115 patients and aimed to determine if rituximab (Rituxan, Genentech) was superior to azathioprine in relapse rates. “Just three patients in the rituximab group, compared to 17 patients in the azathioprine group, experienced a disease relapse by 28 months,” Smith said. “There were a comparable number of adverse events between groups.”
In MAINRITSAN 2, the aim was to use CD19 B cell counts and ANCA to individually tailor a rituximab maintenance regimen and compare relapse rates in patients treated with a fixed regimen. “Results showed that there was no difference in relapse rates with fixed rituximab regimen and individually tailored rituximab infusions,” Smith said.
MAINRITSAN 3 was created to study the optimal duration of therapy in a cohort of 97 patients, according to Smith. They were administered rituximab or placebo at 6, 12 and 18 months, and observed for another 10 months. Results showed that 96% of patients in the rituximab group were in remission at 28 months, compared with 74% in the placebo group.
For the RITAZRAM trial, 197 patients were accrued to address the question of the optimal maintenance strategy following induction, and whether rituximab is superior to azathioprine in prevention of relapse. While rituximab was indeed superior in terms of relapse, Smith noted that when the drug was discontinued, the slope for relapse in the rituximab group was ultimately similar to that of azathioprine. “At the end of 48 months, half of the rituximab group and nearly three-quarters of the azathioprine group had relapsed,” Smith said.
With this information about rituximab discontinuation in mind, Smith raised the question of how the clinical community can arrive at a consensus on the dose and interval for rituximab maintenance therapy beyond 2 years.
She noted that a multidisciplinary team published a set of recommendations last year. While the dosing and interval beyond 2 years have yet to be determined, a fixed interval of either 500 mg or 1,000 mg for a period ranging from 2 to 5 additional years could be considered. “Either 500 mg or 1,000 mg is a reasonable option,” she said.
“The more difficult question is the optimal duration of therapy,” Smith said. She noted that after rituximab has been discontinued, by 4 years, approximately half of patients will have a relapse. An important challenge for the research community will be to determine who is likely to relapse and who is not.
The key consideration, then, is the risk-benefit ratio of discontinuing vs. continuing rituximab. Discontinuing the drug may lead to relapse, organ damage or even death, while continuing may lead to toxicity, serious infections or reduced vaccine efficacy, which Smith suggested is particularly important in the COVID-19 setting.
In addition, hypogammaglobulinemia is a serious risk for patients being treated with rituximab.
In closing, Smith described 500 mg and 1,000 mg as “reasonable choices” for rituximab maintenance dosing. “Maintenance dosing should be at least 2 years, but one could consider extending in high-risk individuals,” she said. “At present, the optimal interval is 6-monthly dosing.”
That said, Smith believes that research will eventually move in the direction of more targeted approaches. “In the future, and in the coming years, we will move away from a 2-year maintenance course of treatment to a much more individually tailored treatment regimen, taking into account the individual’s relapse risk, and the individual’s relapse and infection risks,” Smith said.
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Smith R. Maintenance rituximab in ANCA-associated vasculitis: Dose, frequency, and duration – how do we decide? Presented at: Biologic Therapies Summit IX; May 21-23, 2021 (virtual meeting).
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