Reduced-dose versus high-dose glucocorticoids added to rituximab on remission induction in ANCA-associated vasculitis: predefined 2-year follow-up study
- PMID: 37734880
- DOI: 10.1136/ard-2023-224343
Reduced-dose versus high-dose glucocorticoids added to rituximab on remission induction in ANCA-associated vasculitis: predefined 2-year follow-up study
Abstract
Objectives: The LoVAS trial reported non-inferiority in remission induction rates between the reduced-dose and conventional high-dose glucocorticoid regimens plus rituximab for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 6 months; however, maintenance glucocorticoid requirements and long-term outcomes are unknown.
Methods: A total of 140 patients with new-onset ANCA-associated vasculitis without severe glomerulonephritis or alveolar haemorrhage were randomised to receive reduced-dose prednisolone (0.5 mg/kg/day) plus rituximab (375 mg/m2/week×4) or high-dose prednisolone (1 mg/kg/day) plus rituximab. After achieving remission, patients received the rituximab maintenance therapy (1 g/6 months).
Results: A total of 134 patients were analysed. Among patients who achieved remission with the protocolised treatments, the majority of patients in the reduced-dose group (89.7%) and 15.5% in the high-dose group discontinued prednisolone (median time to withdrawal, 150 and 375 days, respectively). During 24-month trial period, two patients in the reduced-dose group (2.8%) died, while five patients in the high-dose group (7.6%) died (p=0.225). Relapse occurred in nine patients in the reduced-dose group (13.0%) (two major and seven minor) and five in the high-dose group (7.6%) (two major and three minor) (p=0.311). Serious adverse events (SAEs) were less frequent in the reduced-dose group (36 events in 19 patients, 27.5%) than in the high-dose group (54 events in 30 patients, 46.2%) (p=0.025).
Conclusion: At 24 months, frequencies of relapse did not differ between the groups, and SAEs were less frequent in the reduced-dose group due to the lower event rate in the 6-month induction phase. The bias to myeloperoxidase-ANCA positivity (85.8%) in the trial population should be noted.
Trial registration number: NCT02198248.
Keywords: glucocorticoids; rituximab; systemic vasculitis.
© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.
Conflict of interest statement
Competing interests: SF reports receiving lecture fees from Chugai Pharma (Roche group), Asahi Kasei Pharma, Eisai, Daiichi Sankyo and Kissei Pharma and consulting fee from Asahi Kasei Pharma. DN reports receiving grant support and lecture fees from Asahi Kasei Pharma, Chugai Pharma (Roche group), Eisai and Taisho Pharma. MH reports receiving travel support or lecture fees from GlaxoSmithKline, Asahi Kasei Pharma, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, AbbVie, Eli Lilly, Bristol-Myers Squibb, Sanofi, Takeda Pharmaceutical, AstraZeneca, Taisho Pharmaceutical, Pfizer, UCB Japan, Gilead Science, Novartis Pharmaceuticals and Mitsubishi Tanabe Pharma. KA reports receiving lecture fees from AbbVie, Chugai Pharma (Roche group), Eisai, Eli Lilly, GlaxoSmithKleine, Mitsubishi Tanabe Pharma and Pfizer Japan. TU reports receiving lecture fees from Asahi Kasei Pharma, AbbVie GK, Eli Lilly, Mitsubishi Tanabe Pharma and Pfizer, Astellas Pharma, Takeda Pharma, Eisai, Bristol-Myers Squibb and Gilead Sciences. HK reports receiving lecture fees from Chugai Pharma (Roche group), Astellas Pharma, AbbVie, Takeda Pharma, Pfizer, Asahi Kasei Pharma, Eisai and Teijin Pharma. KK reports receiving grant support from AbbVie, Asahi Kasei Pharma, Chugai Pharmaceutical, Eisai, Japan blood products organisation, Mitsubishi Tanabe Pharma, Ono Pharma and Taisyo Pharmaceutical and lecture fees from AbbVie, Asahi Kasei Pharma, Chugai Pharmaceutical, Eli Lilly Japan, Eisai and GSK. RM reports receiving lecture fees from Asahi Kasei Pharma, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Eli Lilly Japan and GSK. YKa reports receiving grant or lecture fees from AbbVie, Asahi Kasei Pharma, Astellas Pharma, Ayumi, Bristol-Myers Squibb, Chugai Pharma, Daiichi Sankyo, Eisai, Eli Lilly, Jansen, Kirin, Novartis Pharma, Pfizer, Sanofi, Takeda Pharma, Mitsubishi Tanabe Pharma and UCB. KH reports receiving consulting fee from GSK, grant support from Chugai Pharma, GSK, Bayer Yakuhin and Kyowa Kirin, and lecture fees from Chugai Pharma, Astellas Pharma, AstraZeneca, Sanofi, GSK and Asahi Kasei Pharma. S-iK reports receiving lecture fees from Janssen Pharmaceutical, AbbVie and VIATRIS and consulting fee from Asahi Kasei Pharma. KI reports receiving grant support from Mitsubishi Tanabe Pharma and lecture fees from Mitsubishi Tanabe Pharma, Bristol-Myers Squibb, Novartis Pharma, AbbVie, Gilead Sciences, Eisai and Eli Lilly. HN reports receiving grant support or lecture fees from Chugai Pharma (Roche group), Bristol-Myers Squibb, Asahi Kasei Pharma, Mitsubishi Tanabe Pharma, Eli Lilly Japan, Eisai, AbbVie, GSK, Sanofi, Novartis Pharma, AstraZeneca and Astellas Pharma. Any pharmaceutical company was not involved in the planning of the protocol or in the conduct of the trial. No other potential conflict of interest relevant to this article was reported.
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