Reduced-Dose Noninferior to High-Dose Glucocorticoid Regimen for ANCA-Associated Vasculitis Remission Induction

For patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), a reduced-dose glucocorticoid plus rituximab regimen was noninferior to a high-dose glucocorticoid plus rituximab regimen for remission induction at 6 months, according to study results published in JAMA.

To compare efficacy and adverse events of the reduced-dose and the high-dose glucocorticoid plus rituximab regimens, patients with newly diagnosed AAV without severe glomerulonephritis or alveolar hemorrhage were enrolled in a phase 4, multicenter, open-label, randomized, noninferiority trial (ClinicalTrials.gov Identifier: NCT02198248).

Of 140 patients (mean age, 73 years; 57.8% women) included in the study, 70 patients received reduced-dose prednisolone (0.5 mg/kg/d) plus rituximab (375 mg/m²/wk; 4 doses) and 70 received high-dose prednisolone (1 mg/kg/d) plus rituximab. A total of 134 participants completed the study.

At 6 months, 49 of 69 (71.0%) patients in the reduced-dose group and 45 of 65 (69.2%) patients in the high-dose group achieved remission. The treatment difference between groups was 1.8 percentage points (1-sided 97.5% CI, -13.7 to ∞), which met the noninferiority criterion (P =.003 for noninferiority). In the reduced-dose group, early relapse occurred in 3 patients while no early relapses occurred in the high-dose group; the frequencies were not statistically different. In the reduced- and high-dose groups, 2 and 3 deaths occurred, respectively, but they were not statistically different.

In the reduced-dose group, serious adverse events were less frequent with 21 events occurring in 13 patients (18.8%) while 41 events in 24 patients (36.9%) occurred in the high dose group (difference, -18.1%; 95% CI, -33.0% to -3.2%; P =.02). The frequency of serious infections was also lower in the reduced-dose compared with the high-dose group; 7 events in 5 patients (7.2%) and 20 events in 13 patients (20.0%), respectively (difference, -12.8%; 95% CI, -24.2% to -1.3%; P =.04). The predefined glucocorticoid-related adverse events, diabetes, insomnia, and all infections also occurred less frequently in the reduced-dose group.

There were several study limitations. The trial was open label; the primary endpoint was assessed using both subjective and objective measures; disease phenotypes were representative of Japanese patients because the trial took place within the single nation of Japan; only newly diagnosed patients without comorbidities requiring glucocorticoids were included in the study; and the basis for setting the noninferiority margin was weak and potentially too wide.

According to the researchers, “To our knowledge, this is the first trial in ANCA-associated vasculitis showing that a lower glucocorticoid dose may reduce serious adverse events.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Furuta S, Nakagomi D, Kobayashi Y, et al; LoVAS Collaborators. Effect of reduced-dose vs high-dose glucocorticoids added to rituximab on remission induction in ANCA-associated vasculitis a randomized clinical trial. JAMA. 2021;325(21):2178-2187. doi:10.1001/jama.2021.6615