Abstract | Importance: Objective: 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: 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: Trial Registration: ClinicalTrials.gov Identifier: NCT02198248.
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Authors | Shunsuke Furuta, Daiki Nakagomi, Yoshihisa Kobayashi, Masaki Hiraguri, Takao Sugiyama, Koichi Amano, Takeshi Umibe, Hajime Kono, Kazuhiro Kurasawa, Yasuhiko Kita, Ryutaro Matsumura, Yuko Kaneko, Keita Ninagawa, Keiju Hiromura, Shin-Ichiro Kagami, Yosuke Inaba, Hideki Hanaoka, Kei Ikeda, Hiroshi Nakajima, LoVAS Collaborators |
Journal | JAMA
(JAMA)
Vol. 325
Issue 21
Pg. 2178-2187
(06 01 2021)
ISSN: 1538-3598 [Electronic] United States |
PMID | 34061144
(Publication Type: Clinical Trial, Phase IV, Comparative Study, Equivalence Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Glucocorticoids
- Immunoglobulin G
- Rituximab
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Topics |
- Aged
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
(drug therapy)
- Dose-Response Relationship, Drug
- Drug Therapy, Combination
- Glucocorticoids
(administration & dosage, adverse effects)
- Humans
- Immunoglobulin G
(blood)
- Male
- Middle Aged
- Remission Induction
- Rituximab
(administration & dosage, adverse effects)
- Severity of Illness Index
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