H Henry Li, Emel Aygören-Pürsün, Markus Magerl, Timothy J Craig, Michael E Manning, Noemi Hummel, Agnieszka Kopiec, Shuai Fu, James Morris, Alice Wang, Paul K Audhya, Jonathan A Bernstein
{"title":"口服sebetralstat和静脉注射重组人C1酯酶抑制剂治疗遗传性血管性水肿发作的间接治疗比较。","authors":"H Henry Li, Emel Aygören-Pürsün, Markus Magerl, Timothy J Craig, Michael E Manning, Noemi Hummel, Agnieszka Kopiec, Shuai Fu, James Morris, Alice Wang, Paul K Audhya, Jonathan A Bernstein","doi":"10.1186/s13223-025-00955-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The goal of on-demand treatment for hereditary angioedema attacks is to halt attack progression to minimize morbidity and mortality. Four on-demand treatments have been approved thus far (ecallantide, icatibant, recombinant human C1 esterase inhibitor [rhC1INH], and plasma-derived C1INH). Results from the sebetralstat phase 3 KONFIDENT trial (NCT05259917) have been reported. To put these results into context without head-to-head trials, an indirect treatment comparison (ITC) was conducted to facilitate comparisons of efficacy and safety across treatment options.</p><p><strong>Methods: </strong>Based on a systematic literature review and feasibility assessment, only the pivotal trial for intravenous rhC1INH (NCT01188564) reported necessary data for a comparable primary efficacy endpoint (time to beginning of symptom relief) to enable an ITC with oral sebetralstat. Bayesian fixed-effects network meta-analyses models were conducted to indirectly compare the efficacy and safety outcomes of sebetralstat and rhC1INH (NCT01188564, NCT00225147, NCT00262301). A matching-adjusted indirect comparison (MAIC) of efficacy was performed, adjusting for baseline attack severity and demographic characteristics.</p><p><strong>Results: </strong>The fixed-effects model found no significant differences in time to beginning of symptom relief between sebetralstat 300 mg and rhC1INH 50 IU/kg (hazard ratio [95% credible interval], 0.96 [0.42-2.15] to 1.19 [0.58-2.45]). After adjusting for baseline attack severity, the MAIC showed numerically favorable results with sebetralstat compared with rhC1INH, regardless of whether baseline demographics were matched. The fixed-effects model found no significant differences in treatment-related treatment-emergent adverse events. All sensitivity analyses returned consistent results.</p><p><strong>Conclusions: </strong>This ITC found no significant differences in time to beginning of symptom relief and overall treatment-related treatment-emergent adverse events between sebetralstat and rhC1INH.</p>","PeriodicalId":51302,"journal":{"name":"Allergy Asthma and Clinical Immunology","volume":"21 1","pages":"10"},"PeriodicalIF":2.6000,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909897/pdf/","citationCount":"0","resultStr":"{\"title\":\"Indirect treatment comparison of oral sebetralstat and intravenous recombinant human C1 esterase inhibitor for on-demand treatment of hereditary angioedema attacks.\",\"authors\":\"H Henry Li, Emel Aygören-Pürsün, Markus Magerl, Timothy J Craig, Michael E Manning, Noemi Hummel, Agnieszka Kopiec, Shuai Fu, James Morris, Alice Wang, Paul K Audhya, Jonathan A Bernstein\",\"doi\":\"10.1186/s13223-025-00955-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The goal of on-demand treatment for hereditary angioedema attacks is to halt attack progression to minimize morbidity and mortality. Four on-demand treatments have been approved thus far (ecallantide, icatibant, recombinant human C1 esterase inhibitor [rhC1INH], and plasma-derived C1INH). Results from the sebetralstat phase 3 KONFIDENT trial (NCT05259917) have been reported. To put these results into context without head-to-head trials, an indirect treatment comparison (ITC) was conducted to facilitate comparisons of efficacy and safety across treatment options.</p><p><strong>Methods: </strong>Based on a systematic literature review and feasibility assessment, only the pivotal trial for intravenous rhC1INH (NCT01188564) reported necessary data for a comparable primary efficacy endpoint (time to beginning of symptom relief) to enable an ITC with oral sebetralstat. Bayesian fixed-effects network meta-analyses models were conducted to indirectly compare the efficacy and safety outcomes of sebetralstat and rhC1INH (NCT01188564, NCT00225147, NCT00262301). A matching-adjusted indirect comparison (MAIC) of efficacy was performed, adjusting for baseline attack severity and demographic characteristics.</p><p><strong>Results: </strong>The fixed-effects model found no significant differences in time to beginning of symptom relief between sebetralstat 300 mg and rhC1INH 50 IU/kg (hazard ratio [95% credible interval], 0.96 [0.42-2.15] to 1.19 [0.58-2.45]). After adjusting for baseline attack severity, the MAIC showed numerically favorable results with sebetralstat compared with rhC1INH, regardless of whether baseline demographics were matched. The fixed-effects model found no significant differences in treatment-related treatment-emergent adverse events. All sensitivity analyses returned consistent results.</p><p><strong>Conclusions: </strong>This ITC found no significant differences in time to beginning of symptom relief and overall treatment-related treatment-emergent adverse events between sebetralstat and rhC1INH.</p>\",\"PeriodicalId\":51302,\"journal\":{\"name\":\"Allergy Asthma and Clinical Immunology\",\"volume\":\"21 1\",\"pages\":\"10\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-03-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909897/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Allergy Asthma and Clinical Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13223-025-00955-6\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Allergy Asthma and Clinical Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13223-025-00955-6","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ALLERGY","Score":null,"Total":0}
Indirect treatment comparison of oral sebetralstat and intravenous recombinant human C1 esterase inhibitor for on-demand treatment of hereditary angioedema attacks.
Background: The goal of on-demand treatment for hereditary angioedema attacks is to halt attack progression to minimize morbidity and mortality. Four on-demand treatments have been approved thus far (ecallantide, icatibant, recombinant human C1 esterase inhibitor [rhC1INH], and plasma-derived C1INH). Results from the sebetralstat phase 3 KONFIDENT trial (NCT05259917) have been reported. To put these results into context without head-to-head trials, an indirect treatment comparison (ITC) was conducted to facilitate comparisons of efficacy and safety across treatment options.
Methods: Based on a systematic literature review and feasibility assessment, only the pivotal trial for intravenous rhC1INH (NCT01188564) reported necessary data for a comparable primary efficacy endpoint (time to beginning of symptom relief) to enable an ITC with oral sebetralstat. Bayesian fixed-effects network meta-analyses models were conducted to indirectly compare the efficacy and safety outcomes of sebetralstat and rhC1INH (NCT01188564, NCT00225147, NCT00262301). A matching-adjusted indirect comparison (MAIC) of efficacy was performed, adjusting for baseline attack severity and demographic characteristics.
Results: The fixed-effects model found no significant differences in time to beginning of symptom relief between sebetralstat 300 mg and rhC1INH 50 IU/kg (hazard ratio [95% credible interval], 0.96 [0.42-2.15] to 1.19 [0.58-2.45]). After adjusting for baseline attack severity, the MAIC showed numerically favorable results with sebetralstat compared with rhC1INH, regardless of whether baseline demographics were matched. The fixed-effects model found no significant differences in treatment-related treatment-emergent adverse events. All sensitivity analyses returned consistent results.
Conclusions: This ITC found no significant differences in time to beginning of symptom relief and overall treatment-related treatment-emergent adverse events between sebetralstat and rhC1INH.
期刊介绍：
Allergy, Asthma & Clinical Immunology (AACI), the official journal of the Canadian Society of Allergy and Clinical Immunology (CSACI), is an open access journal that encompasses all aspects of diagnosis, epidemiology, prevention and treatment of allergic and immunologic disease.
By offering a high-visibility forum for new insights and discussions, AACI provides a platform for the dissemination of allergy and clinical immunology research and reviews amongst allergists, pulmonologists, immunologists and other physicians, healthcare workers, medical students and the public worldwide.
AACI reports on basic research and clinically applied studies in the following areas and other related topics: asthma and occupational lung disease, rhinoconjunctivitis and rhinosinusitis, drug hypersensitivity, allergic skin diseases, urticaria and angioedema, venom hypersensitivity, anaphylaxis and food allergy, immunotherapy, immune modulators and biologics, immune deficiency and autoimmunity, T cell and B cell functions, regulatory T cells, natural killer cells, mast cell and eosinophil functions, complement abnormalities.
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