Rituximab superior to cyclophosphamide in GPA remission induction
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In patients with granulomatosis with polyangiitis, those who start induction therapy with rituximab are more likely to achieve remission compared with those who begin cyclophosphamide, according to data published in JAMA Network Open.
“Results of randomized clinical trials showed rituximab’s noninferiority to cyclophosphamide for remission induction in severe [ANCA-associated vasculitides (AAVs)], with neither treatment having a specific advantage for GPA in adjusted analyses,” Xavier Puéchal, MD, PhD, of the Hôpital Cochin, in Paris, and colleagues wrote. “However, post hoc analysis of the trial data showed that rituximab-treated patients with [ANCA-targeting proteinase 3 (PR3)-AAV] achieved complete remission at 6 months more frequently than cyclophosphamide-treated patients.
“Trial limitations included the enrollment of patients with GPA or microscopic polyangiitis, who might need to be studied separately; small sample size owing to the rarity of those AAVs; and highly selected patients with minor comorbidities that precluded generalization,” they added. “... Thus, it remains to be established whether rituximab is more effective than cyclophosphamide at specifically achieving GPA remission.”
To compare the effectiveness of rituximab (Rituxan, Genentech) and cyclophosphamide in inducing remission in patients with GPA, Puéchal and colleagues conducted a comparative effectiveness study using observational data from 32 hospitals in France. Patients were included if they had newly diagnosed or relapsed GPA. For this analysis, the researchers defined active disease as a Birmingham Vasculitis Activity Score (BVAS) of three or more. Patients also needed to have received rituximab or cyclophosphamide between April 1, 2008, and April 1, 2018.
Meanwhile, patients were excluded if they demonstrated an associated autoimmune disease or an active or previous malignant disease. Those who previously received rituximab or cyclophosphamide within 4 months of enrollment, had a history of therapy-related adverse events or limited GPA were also excluded from the analysis.
The researchers compared data from patients receiving rituximab or cyclophosphamide, and sorted them into groups depending on which intervention they received first. Upon achieving remission, patients were maintained using azathioprine, methotrexate or low doses of rituximab.
The primary outcome was the percentage of patients who achieved remission at 6 months. Secondary endpoints included the percentages of patients who achieved a BVAS score of zero at 6 months, the rate of patients who were retrained without failure at 24 months and safety outcomes at 6 months.
A total of 194 patients were included in the analysis, of whom 61 received rituximab and 133 received cyclophosphamide. According to the researchers, the weighted analysis demonstrated that 73.1% of patients who received rituximab achieved remission at 6 months, compared with 40.1% in the cyclophosphamide group (RR = 1.82; 95% CI, 1.22-2.73), representing a risk difference of 33% 94% CI, 12.2% to 53.8%).
The researchers noted similar results among a subgroup of 165 patients with newly diagnosed GPA and those with a more recent treatment. In the subset of 27 patients with myeloperoxidase-ANCA-positive GPA, 8 of 10 rituximab users, and 8 of 17 cyclophosphamide recipients, achieved the primary end point (unweighted RR = 1.73; 95% CI, 0.96-3.11).
“The findings of this target trial emulation suggest that patients with GPA obtained remission with a prednisone dose of 10 mg/d or less more frequently when they had received rituximab rather than cyclophosphamide for induction therapy,” Puéchal and colleagues wrote. “Our results may inform clinical decision-making concerning the choice of remission induction therapy for this subset of patients with AAV.”
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