Shunsuke Furuta, Daiki Nakagomi, Yoshihisa Kobayashi, et al<\/h3>\n\n\n\nJAMA. <\/em>2021;325(21):2178-2187. doi:10.1001\/jama.2021.6615<\/h3>\n\n\n\nAbstract<\/h2>\n\n\n\nImportance<\/strong><\/h3>\n\n\n\nThe current standard induction therapy for antineutrophil cytoplasm antibody (ANCA)\u2013associated 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.<\/p>\n\n\n\n
Objective<\/strong><\/h3>\n\n\n\nTo 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.<\/p>\n\n\n\n
Design, Setting, and Participants<\/strong><\/h3>\n\n\n\nThis 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.<\/p>\n\n\n\n
Interventions<\/strong><\/h3>\n\n\n\nPatients were randomized to receive reduced-dose prednisolone (0.5 mg\/kg\/d) plus rituximab (375 mg\/m2<\/sup>\/wk, 4 doses) (n\u2009=\u200970) or high-dose prednisolone (1 mg\/kg\/d) plus rituximab (n\u2009=\u200970).<\/p>\n\n\n\nMain Outcomes and Measures<\/strong><\/h3>\n\n\n\nThe primary end point was the remission rate at 6 months, and the prespecified noninferiority margin was \u221220 percentage points. There were 8 secondary efficacy outcomes and 6 secondary safety outcomes, including serious adverse events and infections.<\/p>\n\n\n\n
Results<\/strong><\/h3>\n\n\n\nAmong 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, \u221213.7 to \u221e) between the groups met the noninferiority criterion (P<\/em>\u2009=\u2009.003 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, \u221218.1% [95% CI, \u221233.0% to \u22123.2%]; P<\/em>\u2009=\u2009.02). 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, \u221212.8% [95% CI, \u221224.2% to \u22121.3%]; P<\/em>\u2009=\u2009.04).<\/p>\n\n\n\n![\"\"\/](\"https:\/\/cdn.jamanetwork.com\/ama\/content_public\/journal\/jama\/938707\/m_joi210044va_1621623369.89359.png?Expires=1629532079&Signature=eeJnkPCvMGgVi4WAw53qwI78Hq2T~oJPLe6kC~kb9K9iCJhQXPob4yFbwPtVn-V4Wt3-n38-WXmfAPq7V6SXHhUdqCFlk8Ib8~RmhuQyLC8WAJaD1uk6~o2p3GlqBkAby9ZsZ7QiED6yH-VhWTvxYtLpXtmckC~1M5NAzyW-k4mKbEr4VJ5Gn0WoL5cghqfwH2yLRod05Ew0FgJwKEJEPtr~jGA-efjxn1pu7tLe5g2lcpbwiOKK1I-ommr5IU0U925Mt0ku5-BLMQ8sUUVGz8Fns9Kv2O2t79P361qWBHmn-q-41AP-AISpDNh39qFOKjRvK5TWyC2JWbN~Vixn3A__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA\")
<\/figure>\n\n\n\nConclusions and Relevance<\/strong><\/h3>\n\n\n\nAmong 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.<\/p>\n\n\n\n
Trial Registration<\/strong><\/h3>\n\n\n\n
Abstract<\/h2>\n\n\n\nImportance<\/strong><\/h3>\n\n\n\nThe current standard induction therapy for antineutrophil cytoplasm antibody (ANCA)\u2013associated 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.<\/p>\n\n\n\n
Objective<\/strong><\/h3>\n\n\n\nTo 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.<\/p>\n\n\n\n
Design, Setting, and Participants<\/strong><\/h3>\n\n\n\nThis 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.<\/p>\n\n\n\n
Interventions<\/strong><\/h3>\n\n\n\nPatients were randomized to receive reduced-dose prednisolone (0.5 mg\/kg\/d) plus rituximab (375 mg\/m2<\/sup>\/wk, 4 doses) (n\u2009=\u200970) or high-dose prednisolone (1 mg\/kg\/d) plus rituximab (n\u2009=\u200970).<\/p>\n\n\n\nMain Outcomes and Measures<\/strong><\/h3>\n\n\n\nThe primary end point was the remission rate at 6 months, and the prespecified noninferiority margin was \u221220 percentage points. There were 8 secondary efficacy outcomes and 6 secondary safety outcomes, including serious adverse events and infections.<\/p>\n\n\n\n
Results<\/strong><\/h3>\n\n\n\nAmong 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, \u221213.7 to \u221e) between the groups met the noninferiority criterion (P<\/em>\u2009=\u2009.003 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, \u221218.1% [95% CI, \u221233.0% to \u22123.2%]; P<\/em>\u2009=\u2009.02). 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, \u221212.8% [95% CI, \u221224.2% to \u22121.3%]; P<\/em>\u2009=\u2009.04).<\/p>\n\n\n\n<\/figure>\n\n\n\nConclusions and Relevance<\/strong><\/h3>\n\n\n\nAmong 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.<\/p>\n\n\n\n
Trial Registration<\/strong><\/h3>\n\n\n\n
The current standard induction therapy for antineutrophil cytoplasm antibody (ANCA)\u2013associated 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.<\/p>\n\n\n\n
Objective<\/strong><\/h3>\n\n\n\nTo 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.<\/p>\n\n\n\n
Design, Setting, and Participants<\/strong><\/h3>\n\n\n\nThis 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.<\/p>\n\n\n\n
Interventions<\/strong><\/h3>\n\n\n\nPatients were randomized to receive reduced-dose prednisolone (0.5 mg\/kg\/d) plus rituximab (375 mg\/m2<\/sup>\/wk, 4 doses) (n\u2009=\u200970) or high-dose prednisolone (1 mg\/kg\/d) plus rituximab (n\u2009=\u200970).<\/p>\n\n\n\nMain Outcomes and Measures<\/strong><\/h3>\n\n\n\nThe primary end point was the remission rate at 6 months, and the prespecified noninferiority margin was \u221220 percentage points. There were 8 secondary efficacy outcomes and 6 secondary safety outcomes, including serious adverse events and infections.<\/p>\n\n\n\n
Results<\/strong><\/h3>\n\n\n\nAmong 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, \u221213.7 to \u221e) between the groups met the noninferiority criterion (P<\/em>\u2009=\u2009.003 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, \u221218.1% [95% CI, \u221233.0% to \u22123.2%]; P<\/em>\u2009=\u2009.02). 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, \u221212.8% [95% CI, \u221224.2% to \u22121.3%]; P<\/em>\u2009=\u2009.04).<\/p>\n\n\n\n<\/figure>\n\n\n\nConclusions and Relevance<\/strong><\/h3>\n\n\n\nAmong 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.<\/p>\n\n\n\n
Trial Registration<\/strong><\/h3>\n\n\n\n
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.<\/p>\n\n\n\n
Interventions<\/strong><\/h3>\n\n\n\nPatients were randomized to receive reduced-dose prednisolone (0.5 mg\/kg\/d) plus rituximab (375 mg\/m2<\/sup>\/wk, 4 doses) (n\u2009=\u200970) or high-dose prednisolone (1 mg\/kg\/d) plus rituximab (n\u2009=\u200970).<\/p>\n\n\n\nMain Outcomes and Measures<\/strong><\/h3>\n\n\n\nThe primary end point was the remission rate at 6 months, and the prespecified noninferiority margin was \u221220 percentage points. There were 8 secondary efficacy outcomes and 6 secondary safety outcomes, including serious adverse events and infections.<\/p>\n\n\n\n
Results<\/strong><\/h3>\n\n\n\nAmong 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, \u221213.7 to \u221e) between the groups met the noninferiority criterion (P<\/em>\u2009=\u2009.003 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, \u221218.1% [95% CI, \u221233.0% to \u22123.2%]; P<\/em>\u2009=\u2009.02). 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, \u221212.8% [95% CI, \u221224.2% to \u22121.3%]; P<\/em>\u2009=\u2009.04).<\/p>\n\n\n\n<\/figure>\n\n\n\nConclusions and Relevance<\/strong><\/h3>\n\n\n\nAmong 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.<\/p>\n\n\n\n
Trial Registration<\/strong><\/h3>\n\n\n\n
Main Outcomes and Measures<\/strong><\/h3>\n\n\n\nThe primary end point was the remission rate at 6 months, and the prespecified noninferiority margin was \u221220 percentage points. There were 8 secondary efficacy outcomes and 6 secondary safety outcomes, including serious adverse events and infections.<\/p>\n\n\n\n
Results<\/strong><\/h3>\n\n\n\nAmong 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, \u221213.7 to \u221e) between the groups met the noninferiority criterion (P<\/em>\u2009=\u2009.003 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, \u221218.1% [95% CI, \u221233.0% to \u22123.2%]; P<\/em>\u2009=\u2009.02). 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, \u221212.8% [95% CI, \u221224.2% to \u22121.3%]; P<\/em>\u2009=\u2009.04).<\/p>\n\n\n\n<\/figure>\n\n\n\nConclusions and Relevance<\/strong><\/h3>\n\n\n\nAmong 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.<\/p>\n\n\n\n
Trial Registration<\/strong><\/h3>\n\n\n\n
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, \u221213.7 to \u221e) between the groups met the noninferiority criterion (P<\/em>\u2009=\u2009.003 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, \u221218.1% [95% CI, \u221233.0% to \u22123.2%]; P<\/em>\u2009=\u2009.02). 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, \u221212.8% [95% CI, \u221224.2% to \u22121.3%]; P<\/em>\u2009=\u2009.04).<\/p>\n\n\n\n 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.<\/p>\n\n\n\n<\/figure>\n\n\n\nConclusions and Relevance<\/strong><\/h3>\n\n\n\n
Trial Registration<\/strong><\/h3>\n\n\n\n