1084: Rituximab versus Cyclophosphamide for Induction Therapy in Granulomatosis with Polyangiitis: A Target Trial Emulation Study

Xavier Puéchal¹, Michele Iudici², Elodie Perrodeau³, bernard bonnotte⁴, Francois Lifermann⁵, Thomas Le Gallou⁶, Alexandre Karras⁷, Claire Blanchard-Delaunay⁸, Thomas Quéméneur⁹, Achille Aouba¹⁰, Olivier Aumaître¹¹, Vincent Cottin¹², Mohamed Hamidou¹³, Marc Ruivard¹¹, Pascal Cohen¹, Luc Mouthon¹, Loïc Guillevin¹, Philippe Ravaud³, Raphaël Porcher³ and Benjamin Terrier¹, ¹National Referral Center for Rare Systemic Autoimmune Diseases, Cochin Hospital, Paris, France, ²Division of Rheumatology, Geneva University Hospitals, Geneva, Switzerland, ³Université Paris Cité, Hôtel-Dieu, Paris, France, ⁴Centre Hospitalo-Universitaire de Dijon, Dijon, France, ⁵Dax Hospital, Dax, France, ⁶Rennes Sud University Hospital, Rennes, France, ⁷HEGP, Paris, France, ⁸Niort Hospital, Niort, France, ⁹Valenciennes Hospital, Valenciennes, France, ¹⁰Department of Internal Medicine, UR4650 PSIR, Normandie Univ, UNICAEN, CHU de Caen Normandie, Caen, France, ¹¹Clermont Ferrand University Hospital, Clermont-Ferrand, France, ¹²Coordinating Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, University of Lyon, INRAE, Lyon, France, ¹³Nantes University Hospital, Nantes, France

Background/Purpose: Randomized controlled trials showed rituximab (RTX)'s non-inferiority to cyclophosphamide (CYC) for induction therapy of ANCA-associated vasculitis and neither treatment was favoured in granulomatosis with polyangiitis (GPA). The objective of this study was to compare RTX and CYC to induce remission among a large number of unselected GPA patients.

Methods: We emulated a target trial using observational data collected into the French Vasculitis Study Group Registry. We included newly-diagnosed or relapsing GPA patients satisfying ACR classification criteria and/or Chapel Hill nomenclature between April 2008 and 2018, who had received either RTX or CYC induction treatment. The treatment groups were determined according to observed treatments, with no intervention/experimentation whatsoever from the investigators. Propensity score-based methods were used to correct for imbalance in the groups at baseline. Missing data were handled by multiple imputation. The primary outcome was remission rate at month 6 (± 2 months) defined by BVAS=0 and prednisone daily dose ≤10 mg. Secondary outcomes included the rate of patients with BVAS=0 at months 6 ± 2 months, at any prednisone dose.

Results: 194 GPA patients were included, mean age 54 years, new diagnosis in 165 (85%), PR3-ANCA positivity in 147 (81%); 61 received RTX and 133 CYC as induction therapy. In the weighted analysis, the primary outcome was reached in 75.5% vs 41.3% patients receiving RTX and CYC, respectively (relative risk, 1.83 [95% CI 1.39 to 2.41], risk difference +37.6% [95% CI 34.2 to 49.6], E-value for RR 3.06). In the subset of 27 MPO-ANCA–positive GPA patients, 8/10 and 8/17 in the RTX and CYC groups, respectively, met the primary endpoint (unweighted relative risk, 1.74 [95% CI 0.96 to 3.18]). The number of patients who achieved a BVAS of 0 at 6 months ± 2 months, without taking into account the prednisone dose, was 47/55 (85.4%) and 95/115 (82.6%) in the RTX and CYC group, respectively.

Conclusion: This emulated trial in GPA patients shows that RTX as induction therapy is associated with more frequent achievement of remission than CYC in real-world data.
Comparative analyses for rate of remission and achievement of BVAS = 0 at 6 months ± 2 months
Disclosures: X. Puéchal, Roche; M. Iudici, None; E. Perrodeau, None; b. bonnotte, Roche; F. Lifermann, Roche; T. Le Gallou, Roche; A. Karras, Roche, Gilead, Amgen; C. Blanchard-Delaunay, Roche; T. Quéméneur, Roche; A. Aouba, Roche; O. Aumaître, Roche; V. Cottin, Boehringer Ingelheim, Roche, Shionogi, RedX, PureTech, Celgene/BMS, AstraZeneca, XSL Behring, Sanofi, United Therapeutics, Pliant, Boehringer Ingelheim, Roche, Galapagos, Celgene/BMS, CSL Behring, Galecto, Fibrogen; M. Hamidou, Roche; M. Ruivard, Roche; P. Cohen, Roche; L. Mouthon, Boehringer-Ingelheim, LFB; L. Guillevin, Roche; P. Ravaud, None; R. Porcher, None; B. Terrier, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb(BMS), Eli Lilly, LFB, Boehinger Ingelheim, Vifor Pharma, Pfizer, Roche.