More patients with granulomatosis with polyangiitis (GPA) were in remission at 6 months if they had received rituximab (Rituxan) rather than cyclophosphamide (Cytoxan) as induction therapy, according to a target trial emulation performed by the French Vasculitis Study Group (FVSG).
Remission, which was defined as a score of zero on the validated Birmingham Vasculitis Activity Score (BVAS) and use of no more than 10 mg of prednisone a day, was documented in 73.1% of rituximab-treated patients and 40.1% of cyclophosphamide-treated patients.
Similar rates of remission were observed regardless of whether patients were newly diagnosed with GPA (76.1% vs. 41.6%) or had been recently treated for relapsing disease (75.2% vs. 44.5%), FVSG researchers reported in JAMA Network Open.
This research “may inform clinical decision-making regarding the choice of remission-inducing regimen for patients with GPA,” the researchers suggested.
Practice already shifting to rituximab
“The results are largely in line with previous perceptions,” David R.W. Jayne, MD, honorary consultant and director of the vasculitis and lupus service at Addenbrooke’s Hospital in Cambridge, England, observed in an emailed comment.
Dr. David R.W. Jayne
“The difference is a bit bigger [in favor of rituximab] than I would have expected,” said Dr. Jayne, who is also professor of clinical autoimmunity at the University of Cambridge. He noted that clinical practice was already moving toward using rituximab in place of cyclophosphamide.
Rituximab gained a European license to treat antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides (AAV) just over a decade ago. Since then, it has slowly started to replace the use of cyclophosphamide and glucocorticoids, which were the preferred method up until then.
Part of the reason for this shift is the toxicity associated with cyclophosphamide, although that’s not to say that rituximab is free from safety concerns, Dr. Jayne said.
“Toxicity issues with rituximab, especially secondary immunodeficiency, more severe COVID, and blocking vaccine responses, are becoming bigger issues for day-to-day practice,” he noted. Nonetheless, “the introduction of rituximab has been a revolution in AAV treatment. It has encouraged pharma investment in the disease, such as recent approval of avacopan [Tavneos], and it is helping patients.”
Why simulate and not perform a randomized trial?
There were several reasons for performing the current evaluation, study coauthor Benjamin Terrier, MD, PhD, said in an interview.
Dr. Benjamin Terrier
“The pivotal study, published in 2010, that led to the approval of rituximab was a noninferiority study in comparison with cyclophosphamide, but it included patients with both GPA, granulomatosis with polyangiitis, and MPA, microscopic polyangiitis,” explained Dr. Terrier, professor of internal medicine at the National Referral Center for Rare Systemic Autoimmune Diseases at Cochin Hospital in Paris.
“A post hoc analysis showed that, in the patients with a PR3 [proteinase 3]-ANCA and in the patients with relapsing disease, rituximab was superior,” he added.
“So, there was some data which suggest that rituximab could be differentially effective between the different subgroups of patients. So that’s why we wanted to answer this question.”
Since it is not always feasible to do a randomized trial, particularly when it concerns a rare disease such as GPA, Dr. Terrier and associates decided to perform a target trial emulation using data from the FVSG registry, which collates information from 32 hospitals in France. Such studies are gaining in popularity and have been shown to provide a very good level of evidence, he said.