Rituximab vs Cyclophosphamide Induction Therapy for Patients With Granulomatosis With Polyangiitis

Abstract

ImportanceResults 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.ObjectiveTo compare the effectiveness of rituximab and cyclophosphamide in inducing GPA remission in a large population of unselected patients.Design, Setting, and ParticipantsThis 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.ExposuresAt least 1 infusion of rituximab or cyclophosphamide for induction therapy between April 1, 2008, and April 1, 2018.Main Outcomes and MeasuresThe 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.ResultsAmong 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 RelevanceIn 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.

Comparative Effectiveness of Rituximab‐ Versus Cyclophosphamide‐Based Remission Induction Strategies in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis for the Risk of Kidney Failure and Mortality

“…We also investigated 2 secondary outcomes to explore the effects of rituximab‐ versus cyclophosphamide‐based treatment strategies on other clinically relevant outcomes in a real‐world setting. Similar to a recent retrospective cohort study conducted in France that analyzed outcomes in a smaller cohort of patients with mostly PR3‐ANCA+ AAV (33), we found that patients treated with rituximab were more likely to discontinue or achieve a lower dose of prednisone within 6 months of treatment initiation than patients treated with cyclophosphamide. Despite this observation, we found no difference in the risk of severe infection at 1, 2, and 5 years among those treated with rituximab‐ versus cyclophosphamide‐based strategies.…”

Short-term effectiveness and safety of rituximab versus cyclophosphamide for life-threatening ANCA-associated vasculitis: a propensity score analysis of the real-world nationwide database

“…IVCY, which can rapidly and directly damage broader pathogenic cells including T cells, macrophages and neutrophils infiltrating the kidney, may be more immediate and effective than RTX in the treatment of RPGN. The effectiveness of RTX and IVCY may differ depending on the AAV subtype and profile of activated lymphocytes; therefore, individualised consideration of patient background may be necessary for treatment selection in remission induction therapy of life-threatening AAV 30 31. Since this was a retrospective study using a nationwide administrative database, there was no novel information on the immunobiological mechanisms.…”

Disease Modulation Versus Modification: A Call for Revised Outcome Metrics in the Treatment of Thyroid Eye Disease

“…4 Another devastating and persistent systemic disease, granulomatosis with polyangiitis was traditionally managed by disease modulation with extended courses of high-dose CS and cytotoxic agents, which inconsistently induced remission and was associated with significant morbidity. 5,6 More recently, disease modulation has been replaced by highly effective disease modification achieved with B-cell depletion through the use of rituximab, a chimeric monoclonal anti-CD20 antibody, affording long disease-free intervals. 5,6 The superior efficacy and reduced therapeutic morbidity, as compared with prior regimens, far outweighs the rare risk of progressive multifocal leukoencephalopathy (2.5 per 100,000).…”

“…5,6 More recently, disease modulation has been replaced by highly effective disease modification achieved with B-cell depletion through the use of rituximab, a chimeric monoclonal anti-CD20 antibody, affording long disease-free intervals. 5,6 The superior efficacy and reduced therapeutic morbidity, as compared with prior regimens, far outweighs the rare risk of progressive multifocal leukoencephalopathy (2.5 per 100,000). 6,7…”

“…5,6 The superior efficacy and reduced therapeutic morbidity, as compared with prior regimens, far outweighs the rare risk of progressive multifocal leukoencephalopathy (2.5 per 100,000). 6,7…”