Rituximab, cyclophosphamide show similar rates of kidney failure, death in AAV
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Key takeaways:
- Rituximab- and cyclophosphamide-based remission induction for ANCA-associated vasculitis demonstrate similar risks for kidney failure and death.
- Outcomes were similar at 1, 2 and 5-year follow-up.
Remission induction strategies based on rituximab and cyclophosphamide each demonstrate similar risks for kidney failure and death in patients with ANCA-associated vasculitis, according to data published in Arthritis & Rheumatology.
“We performed this study because despite its widespread use to treat AAV since the RAVE trial, there have been few real-world effectiveness studies comparing how patients do with rituximab vs. cyclophosphamide for induction of remission in AAV,” Zachary S. Wallace, MD, MSc, of Massachusetts General Hospital, in Boston, told Healio. “There remains some controversy over whether one or the other may lead to better outcomes because of differences in speed of onset or associated adverse events.”
To compare rituximab (Rituxan, Genentech) and cyclophosphamide-based therapies for remission induction in patients with AAV, Wallace and colleagues conducted a real-world cohort study using the Mass General Brigham AAV cohort. They included consecutive patients with AAV who were diagnosed between Jan. 1, 2002, and June 30, 2019,using electronic medical records to confirm the presence of disease in each patient. Patients with eosinophilic granulomatosis with polyangiitis were excluded from the analysis. The researchers extracted relevant data including demographics, laboratory testing results and medications used.
The exposure of interest was treatment of AVV using rituximab- or cyclophosphamide-based therapies. In addition to the test therapy, each patient also received glucocorticoids. Patients who did not receive rituximab or cyclophosphamide were excluded from the analysis. The primary outcome was the composite reporting of kidney failure or all-cause mortality. Wallace and colleagues also assessed the prevalence of each of those outcomes.
The analysis included 595 patients. Of those, 352 received rituximab while 243 received cyclophosphamide. After 5 years of follow-up, there were 133 events of kidney failure or death. For patients receiving rituximab-based therapies, the rate was 6.8 events per 100 person-years. In patients receiving cyclophosphamide-based treatments, the rate was 6.1 events per 100 person-years, according to the researchers. In addition, rates of kidney failure were similar in both groups (HR = 1.05; 95% CI 0.55-1.93).
“The main takeaway is that the risk of death or end-stage kidney failure at 1, 2 and 5 years of follow up was similar regardless of whether rituximab or cyclophosphamide was used as the induction regimen,” Wallace said.
“Additionally, we found that the risk of severe infection was similar with either regimen, suggesting that other factors — eg, steroid exposure, other medical problems or regimens used to maintain remission — may be better targets for addressing the infection risk in AAV,” he added. “Collectively, I think that these findings are reassuring for contemporary practice where the majority of providers are using rituximab to achieve remission in patients with AAV.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Comparing treatment strategies is very valuable in medicine. For a new treatment strategy to displace an established therapy, it almost always necessitates a cohort analysis comparison, especially when the “challenger” has advantages regarding efficacy, adverse events, dosing or cost.
Cyclophosphamide has been established for remission induction of ANCA-associated vasculitis since the landmark publication by Fauci and Wolff from the NIH in 1973. Rituximab was found to be non-inferior to cyclophosphamide for remission induction of AAV, as reported in separate publications by Jones and Stone in 2010.
Although there was no significant difference in the rates of adverse events between the rituximab (Rituxan, Genentech) and cyclophosphamide groups in the RAVE trial, cyclophosphamide use is associated historically with high rates of death and adverse events related to infertility, infection and cancer, making rituximab seemingly a safer alternative.
This present investigation is concerned with the long-term outcomes of these two remission-inducing strategies regarding kidney failure and death. The majority of this MGB cohort were MPO-ANCA+, unlike the RAVE trial. It revealed that cyclophosphamide and rituximab-based remission induction strategies for AAV were associated with similar risks for kidney failure and death at 5 years and at intermediate evaluation points. The researchers felt that this result should be generalizable to both the MPO-ANCA+ and the PR3-ANCA+ groups.
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