Patients With Granulomatosis With Polyangiitis More Likely to Achieve Remission With Rituximab Than Cyclophosphamide

Induction therapy with rituximab vs cyclophosphamide was more frequently associated with GPA remission.

Disease remission is more frequently associated with rituximab than cyclophosphamide in patients with granulomatosis with polyangiitis (GPA), according to study findings published in JAMA Network Open.

Granulomatosis with polyangiitis is characterized by granulomatous inflammation of small to medium blood vessels, which affects the upper and lower respiratory tracts and causes necrotizing glomerulonephritis.

Researchers in France compared the effectiveness of rituximab and cyclophosphamide in inducing GPA remission.

Between October 2021 and May 2022, they analyzed observational data obtained from the multicenter target trial in the French Vasculitis Study Group (FVSG) Registry across 32 hospitals in France.

Eligible patients with GPA who were exposed to at least 1 infusion of rituximab or cyclophosphamide for induction therapy were included in the study.

These results inform clinical decision-making concerning the choice of remission induction therapy for this subset of patients with AAV.

The primary outcome of the study was remission of GPA after 6 months following induction therapy with rituximab or cyclophosphamide. Remission was defined as a score of 0 on the Birmingham Vasculitis Activity Score (BVAS) and a dose of 10 mg per day or less of prednisone.

A total of 194 patients (mean age, 54 years; 56.7% men) were included in the study, among whom 61 received rituximab and 133 received cyclophosphamide. Of the 194 patients, 165 (85.1%) were newly diagnosed with GPA.

Of 182 patients with available data, 147 (80.8%) tested positive for antineutrophil cytoplasm antibody-targeting proteinase 3 (PR3-ANCA). Ten patients in the rituximab group and 17 patients in the cyclophosphamide group had myeloperoxidase (MPO)-ANCA-positive GPA. Patients with PR3-ANCA-positive GPA were more likely to have relapses.

The researchers observed that 73.1% of patients who received rituximab achieved remission of GPA compared with 40.1% of patients who received cyclophosphamide (relative risk [RR], 1.82; 95% CI, 1.22-2.73). Results were similar with newly diagnosed vs established GPA.

With regard to GPA subgroups, 8 of the 10 patients with MPO-ANCA-positive GPA responded better to rituximab (80% remission rate) compared with the 8 of the 17 patients who received cyclophosphamide (47.1% remission rate; unweighted RR, 1.73 [95% CI, 0.96-3.11]).

After excluding the remission criteria of a prednisone dose of 10 mg per day or less, 85.5% of patients in the rituximab group achieved a BVAS score of 0 after 6 months compared with 82.6% of patients in the cyclophosphamide group.

Study limitations included the lack of randomization due to the observational nature of this analysis; the lack of comparative balance in sample sizes between groups (61 vs 133); potential unmeasured confounding factors; and the exclusion of patients with GPA who received treatment with concurrent methotrexate, azathioprine, or plasma exchanges. In addition, physicians may have transitioned during the 10-year enrollment period to using less glucocorticoids in the induction phase, which may have affected patients in the rituximab group who received treatment later than those in the cyclophosphamide group.

“These results inform clinical decision-making concerning the choice of remission induction therapy for this subset of patients with ANCA [-associated vasculitides],” the study authors concluded.

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original source for full list of disclosures.


Puéchal X, Iudici M, Perrodeau E, et al. Rituximab vs cyclophosphamide induction therapy for patients with granulomatosis with polyangiitis. JAMA Netw Open. 2022;5(11):e2243799. doi:10.1001/jamanetworkopen.2022.43799