Course: Effect of Reduced-Dose vs High-Dose Glucocorticoids Added to Rituximab on Remission Induction in ANCA-Associated Vasculitis: A Randomized Clinical Trial
CME Credits: 1.00
Released: 2021-06-01
Key Points
Question Is a reduced-dose glucocorticoid plus rituximab regimen noninferior to the conventional high-dose glucocorticoid plus rituximab regimen in remission induction of antineutrophil cytoplasm antibody (ANCA)–associated vasculitis?Findings In this randomized clinical trial that included 140 patients with newly diagnosed ANCA-associated vasculitis, the proportion of patients with disease remission at 6 months was 71.0% in the reduced-dose glucocorticoid plus rituximab group and 69.2% in the high-dose glucocorticoid plus rituximab group, a difference that met the prespecified noninferiority margin of -20 percentage points.
Meaning Among patients with newly diagnosed ANCA-associated vasculitis, a reduced-dose glucocorticoid plus rituximab regimen was noninferior to a high-dose glucocorticoid plus rituximab regimen with regard to induction of disease remission.
Abstract
Importance The current standard induction therapy for antineutrophil cytoplasm antibody (ANCA)–associated vasculitis is the combination of high-dose glucocorticoids and cyclophosphamide or rituximab. Although these regimens have high remission rates, they are associated with considerable adverse events presumably due to high-dose glucocorticoids.Objective To compare efficacy and adverse events between a reduced-dose glucocorticoid plus rituximab regimen and the standard high-dose glucocorticoid plus rituximab regimen in remission induction of ANCA-associated vasculitis.
Design, Setting, and Participants This was a phase 4, multicenter, open-label, randomized, noninferiority trial. A total of 140 patients with newly diagnosed ANCA-associated vasculitis without severe glomerulonephritis or alveolar hemorrhage were enrolled between November 2014 and June 2019 at 21 hospitals in Japan. Follow-up ended in December 2019.
Interventions Patients were randomized to receive reduced-dose prednisolone (0.5 mg/kg/d) plus rituximab (375 mg/m2/wk, 4 doses) (n?=-70) or high-dose prednisolone (1 mg/kg/d) plus rituximab (n?=-70).
Main Outcomes and Measures The primary end point was the remission rate at 6 months, and the prespecified noninferiority margin was -20 percentage points. There were 8 secondary efficacy outcomes and 6 secondary safety outcomes, including serious adverse events and infections.
Results Among 140 patients who were randomized (median age, 73 years; 81 women [57.8%]), 134 (95.7%) completed the trial. At 6 months, 49 of 69 patients (71.0%) in the reduced-dose group and 45 of 65 patients (69.2%) in the high-dose group achieved remission with the protocolized treatments. The treatment difference of 1.8 percentage points (1-sided 97.5% CI, -13.7 to ?) between the groups met the noninferiority criterion (P?=?.003 for noninferiority). Twenty-one serious adverse events occurred in 13 patients in the reduced-dose group (18.8%), while 41 occurred in 24 patients in the high-dose group (36.9%) (difference, -18.1% [95% CI, -33.0% to -3.2%]; P?=?.02). Seven serious infections occurred in 5 patients in the reduced-dose group (7.2%), while 20 occurred in 13 patients in the high-dose group (20.0%) (difference, -12.8% [95% CI, -24.2% to -1.3%]; P?=?.04).
Conclusions and Relevance Among patients with newly diagnosed ANCA-associated vasculitis without severe glomerulonephritis or alveolar hemorrhage, a reduced-dose glucocorticoid plus rituximab regimen was noninferior to a high-dose glucocorticoid plus rituximab regimen with regard to induction of disease remission at 6 months.
Trial Registration ClinicalTrials.gov Identifier:
Educational Objective
To learn the effect of reduced-dose glucocorticoids vs standard high-dose glucocorticoids, added to rituximab, on remission induction in patients with antineutrophil cytoplasm antibody (ANCA)–associated vasculitis.
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