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Observational Study
. 2022 Nov 1;5(11):e2243799.
doi: 10.1001/jamanetworkopen.2022.43799.

Rituximab vs Cyclophosphamide Induction Therapy for Patients With Granulomatosis With Polyangiitis

Xavier Puéchal  1 , Michele Iudici  1   2 , Elodie Perrodeau  3 , Bernard Bonnotte  4 , François Lifermann  5 , Thomas Le Gallou  6 , Alexandre Karras  7 , Claire Blanchard-Delaunay  8 , Thomas Quéméneur  9 , Achille Aouba  10 , Olivier Aumaître  11 , Vincent Cottin  12 , Mohamed Hamidou  13 , Marc Ruivard  11 , Pascal Cohen  1 , Luc Mouthon  1 , Loïc Guillevin  1 , Philippe Ravaud  3 , Raphaël Porcher  3 , Benjamin Terrier  1 ; French Vasculitis Study Group
Collaborators, Affiliations
Observational Study

Rituximab vs Cyclophosphamide Induction Therapy for Patients With Granulomatosis With Polyangiitis

Xavier Puéchal et al. JAMA Netw Open. .

Abstract

Importance: Results of randomized clinical trials have demonstrated rituximab's noninferiority to cyclophosphamide as induction therapy for antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), with neither treatment having a specific advantage for granulomatosis with polyangiitis (GPA). However, post hoc analysis results have suggested that rituximab might be more effective than cyclophosphamide in inducing remission in patients with proteinase 3-positive AAV.

Objective: To compare the effectiveness of rituximab and cyclophosphamide in inducing GPA remission in a large population of unselected patients.

Design, setting, and participants: This comparative effectiveness study used multicenter target trial emulation observational data from 32 French hospitals in the French Vasculitis Study Group Registry. Groups were determined according to treatments received, without any intervention from the investigators. Inverse probability of treatment weighting was used to correct for baseline imbalance between groups. Participants included patients with newly diagnosed or relapsing GPA who satisfied American College of Rheumatology classification criteria and/or Chapel Hill Consensus Conference nomenclature. Data were analyzed from October 1, 2021, to May 31, 2022.

Exposures: At least 1 infusion of rituximab or cyclophosphamide for induction therapy between April 1, 2008, and April 1, 2018.

Main outcomes and measures: The primary outcome was remission rate at month 6 (±2 months), with remission defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and prednisone dose of 10 mg/d or less. The BVAS is a validated tool for small-vessel vasculitis and used to assess the level of disease activity, with a numerical weight attached to each involved organ system. The BVAS has a range of 0 to 63 points; a score of 0 indicates no disease activity. Subgroup analyses included the primary outcome for patients with a new diagnosis, for most recently treated patients, and for patients with myeloperoxidase-ANCA positivity.

Results: Among 194 patients with GPA included in the analysis (mean [SD] age, 54 [15] years; 110 men [56.7%]), 165 (85.1%) had a new diagnosis, and 147 of 182 with data available (80.8%) had proteinase 3-ANCA positivity. Sixty-one patients received rituximab and 133 received cyclophosphamide for induction therapy. In the weighted analysis, the primary outcome was reached for 73.1% of patients receiving rituximab vs 40.1% receiving cyclophosphamide (relative risk [RR], 1.82 [95% CI, 1.22-2.73]; risk difference, 33.0% [95% CI, 12.2%-53.8%]; E value for RR, 3.05). Similar results were observed in the subgroup of 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 recipients and 8 of 17 cyclophosphamide recipients met the primary end point (unweighted RR, 1.73 [95% CI, 0.96-3.11]).

Conclusions and relevance: In this comparativeness effectiveness study using clinical data, rituximab induction therapy for GPA was more frequently associated with remission than cyclophosphamide. These results inform clinical decision-making concerning the choice of remission induction therapy for this subset of patients with AAV.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Puéchal reported receiving grant funding from Roche Pharma Ltd and congress registration from GlaxoSmithKline outside the submitted work. Dr Iudici reported receiving speaking fees from Boehringer Ingelheim outside the submitted work. Dr Aouba reported receiving a grant to support postgraduate teaching conferences through his medical association from Roche Pharma Ltd; congress inscription, travel, and accommodation support from Amicus Therapeutics and AstraZeneca; and personal fees from Boehringer Ingelheim outside the submitted work. Dr Aumaître reported receiving grant funding from Roche Pharma Ltd outside the submitted work. Dr Cottin reported receiving personal fees from Boehringer Ingelheim, Roche Pharma Ltd, Redx, PureTech, AstraZeneca, Ferrer, Bristol-Myers Squibb Company, Sanofi SA, CSL Behring, and Pliant outside the submitted work. Dr Cohen reported receiving grant funding from Roche Pharma Ltd outside the submitted work during the conduct of the study. Dr Mouthon reported receiving grant funding from LFB Biotechnologies and Boehringer Ingelheim outside the submitted work. Dr Guillevin reported receiving grant funding from Roche Pharma Ltd and consulting for Roche Pharma Ltd outside the submitted work. Dr Terrier reported receiving personal fees from Vifor Pharma Group, GlaxoSmithKline, and AstraZeneca during the conduct of the study. No other disclosures were reported.

Figures

Figure.
Figure.. Flowchart of Patients With Granulomatosis With Polyangiitis (GPA) Who Received Rituximab (RTX) or Cyclophosphamide (CYC) as Induction Therapy
BVAS indicates Birmingham Vasculitis Activity Score. The BVAS is a validated tool for small-vessel vasculitis and used to assess the level of disease activity, with a numerical weight attached to each involved organ system. The BVAS has a range of 0 to 63 points; a score of 0 indicates no disease activity. aPatients could have more than 1 ineligibility criteria.
See this image and copyright information in PMC

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