Background/Purpose: Organ or life-threatening granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), two of the antineutrophil cytoplasm antibody-associated vasculitis (AAV), are treated with cyclophosphamide or rituximab (RTX) in combination with glucocorticoids. Different RTX regimens for induction of remission are available: the 4-dose AAV regimen at doses of 375 mg/m² I.V. weekly, and the 2-dose rheumatoid arthritis (RA) regimen at doses of 1000 mg I.V. on day 1 and 15. Although the 4-dose regimen has been most extensively studied for induction therapy in AAV, many clinicians choose to use the 2-dose RA regimen to reduce infusion frequency, total dose, and cost. Head-to-head comparative studies of these two regimens have not yet been conducted. Thus, strong evidence is lacking to demonstrate if they are equivalent for the treatment of severe AAV.

The objective of this meta-analysis was to compare the efficacy and safety of these two RTX regimens for the induction of remission in severe AAV.

Methods: A systematic review was performed (PubMed, Cochrane, Google scholar, ClinicalTrials.gov, MEDLINE, and CENTRAL) to identify studies using the 4-dose AAV and/or 2-dose RA rituximab regimens for induction of remission in severe AAV. Availability of disease status 6 months after RTX induction therapy was required for inclusion. Patients were excluded if they received concomitant cyclophosphamide or plasma exchange. The primary endpoint was the proportion of patients in complete remission, which was defined as a BVAS of 0 and/or as the absence of disease activity on clinical assessment. The pooled estimate was obtained using meta-analysis methods for proportions with random effects. Other secondary endpoints at 6 months included ANCA status, number of patients with B cell depletion, mean prednisone dose, infections, and death.

Results: Out of the 3619 studies identified, 27 met inclusion criteria, including 1 RCT, 4 prospective cohorts, 9 retrospective cohorts and 13 case series. A total of 506 patients with GPA or MPA were included for analysis: 361 patients were treated with the 4-dose AAV regimen and 145 patients with the 2-dose RA regimen. Mean age was 50 years, 52% were women, and 86% were ANCA-positive. Relapsing disease at inclusion accounted for 83% and 92% of patients in the 4-dose AAV and the 2-dose RA regimen group, respectively. Overall, complete remission at 6 months was achieved in 88 % (95% CI: 78–95) of patients. There was no significant difference between the 4-dose AAV and 2-dose RA regimens, complete remission reaching respectively 85% (95% CI: 70-96) and 91% (95% CI: 79-99) (fig 1). Results remained consistent after the exclusion of low-quality studies. At 6 months, the mean daily dose of prednisone was 8.1 mg and was comparable in both groups. Both regimens led to a similar proportion of patients with infections (12% in both) and death (1% vs. 0%), respectively, at 6 months, with insufficient data to conclude on other secondary endpoints.

Conclusion: No difference was found in terms of efficacy and safety between the 4-dose AAV and the 2-dose RA rituximab regimens for induction of remission in severe AAV.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparison-of-two-rituximab-regimens-for-induction-of-remission-in-antineutrophil-cytoplasm-antibody-associated-vasculitis-systematic-review-and-meta-analysis/