Rituximab matches cyclophosphamide in inducing AAV remission: Review
Infusion therapy may offer safer, more targeted option for many patients
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Rituximab is at least as effective as cyclophosphamide in inducing remission in people with ANCA-associated vasculitis (AAV), and it may offer a safer, more targeted option for many patients, according to a review study.
“These findings reinforce the evolving role of rituximab as a central component of modern therapeutic strategies for ANCA-associated vasculitis,” researchers wrote.
The study, “Comparison of Rituximab and Cyclophosphamide for Induction Therapy in Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis: A Systematic Review of Randomized Trials and Comparative Cohort Evidence,” was published in the journal Cureus.
AAV treatment decisions remain challenging
AAV is a group of rare autoimmune diseases that cause inflammation and damage in small blood vessels throughout the body. These conditions most often affect the kidneys, lungs, and upper airways, and can quickly become life-threatening without prompt treatment.
“Over the last two decades, outcomes have improved significantly due to the use of effective immunosuppressive regimens,” the researchers wrote. “However, treatment decisions remain challenging because of disease [variability], relapse patterns, and potential medication toxicities.”
For many years, cyclophosphamide (sold as Cytoxan and others, with generics available) was used off-label to control AAV. While effective, this immunosuppressive therapy can cause serious side effects, including infections, infertility, and an increased risk of certain cancers. These concerns led researchers to explore safer, more targeted options.
One such alternative is rituximab, sold as Rituxan in the U.S. and MabThera in Europe, with biosimilars available. It promotes the death of B-cells, the immune cells that play a key role in producing self-reactive antibodies that drive AAV, making it a more targeted therapy.
Rituximab is approved, in combination with standard glucocorticoids, for the treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the two most common AAV types.
Researchers include 4 of 310 studies in final analysis
In this study, a trio of researchers in the U.K. and Pakistan systematically reviewed published studies reporting results from clinical trials and real-world studies that compared rituximab against cyclophosphamide for inducing AAV remission.
The study’s main goals included assessing remission rates and sustained remission, while secondary goals included relapse rates, kidney function recovery, and treatment-related adverse events.
Of the 310 studies identified across three databases, four met the eligibility criteria and were included in the final analysis. Among these, three were appropriately controlled clinical trials and one was an observational, real-world study conducted across multiple French centers.
All studies compared rituximab, given directly into the bloodstream (intravenously), with cyclophosphamide, given orally or intravenously, as first-line (induction) treatments for AAV.
All clinical trials enrolled adults with severe, organ-threatening GPA or MPA. Participants in all studies were followed for at least six months and up to 1.5 years.
Overall, evidence showed that rituximab worked at least as well as cyclophosphamide in inducing disease remission.
Rituximab outperforms cyclophosphamide in real-world study
In the largest clinical trial, involving 197 patients, 64% of those treated with rituximab achieved remission within six months, compared with 53% of those given cyclophosphamide — a statistically significant difference.
Rituximab was also found to be significantly superior to cyclophosphamide in the real-world study, which involved 194 patients, with remission rates of 73.1% and 40.1%, respectively, at six months.
“These observations suggest that rituximab’s clinical advantages may be more pronounced outside of controlled trial settings, where [variability] in disease severity, [simultaneous conditions], and prior treatments is broader,” the team wrote.
However, the researchers noted that rituximab’s superiority in relapse prevention waned over time, with comparable remission rates after 1.5 years. This suggests that “a single induction regimen may not be sufficient for sustained disease control in many patients,” they wrote.
Data also showed that “both treatments demonstrated comparable effectiveness in patients with severe organ involvement,” the team wrote, with similar effects on kidney recovery.
[These findings support rituximab as] “an effective and often preferable alternative to cyclophosphamide for remission induction, offering strong efficacy with a more favorable long-term safety profile, and should be considered a key component of modern treatment algorithms for ANCA-associated vasculitis.
Data from these four studies, along with other published studies, support rituximab as “a strong first-line option, particularly in relapsing disease, PR3-ANCA [AAV], and in patients where avoidance of cyclophosphamide toxicity is a priority,” the team wrote.
PR3-ANCA AAV refers to patients testing positive for self-reactive antibodies against the PR3 protein and who typically experience high relapse rates.
Cyclophosphamide remains an effective option for newly diagnosed patients, especially where access to rituximab may be limited, the team noted.
Overall, these findings support rituximab as “an effective and often preferable alternative to cyclophosphamide for remission induction, offering strong efficacy with a more favorable long-term safety profile, and should be considered a key component of modern treatment algorithms for ANCA-associated vasculitis,” they concluded.
