Regis Peffault de Latour, Austin Kulasekararaj, David Dingli, Koo Wilson, Piotr Wojciechowski, Zalmai Hakimi, Jameel Nazir, Barbara Czech, Peter Hillmen, Jeff Szer
{"title":"锚定间接治疗比较发现佩西卡普兰和伊普他科潘治疗阵发性夜间血红蛋白尿的效果相当。","authors":"Regis Peffault de Latour, Austin Kulasekararaj, David Dingli, Koo Wilson, Piotr Wojciechowski, Zalmai Hakimi, Jameel Nazir, Barbara Czech, Peter Hillmen, Jeff Szer","doi":"10.1111/ejh.14422","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-rare, acquired non-malignant haematological disorder characterised by thrombosis risk, serious complications and debilitating symptoms in untreated patients.</p><p><strong>Objective: </strong>This anchored indirect treatment comparison (ITC) evaluated efficacy data between proximal complement 3 inhibitor (C3i) pegcetacoplan and factor B inhibitor, iptacopan, in patients with PNH previously treated with complement 5 inhibitors (C5i; eculizumab, ravulizumab).</p><p><strong>Methods: </strong>Respective pivotal studies provided patient-level trial data for pegcetacoplan (16-week PEGASUS [NCT03500549]) and published data for iptacopan (24-week APPLY PNH [NCT04558918]). Differences in study design, duration and statistical methods between PEGASUS and APPLY PNH necessitated the comparative analyses to be conducted on secondary measures based on haemoglobin (Hb) levels, absolute reticulocyte count (ARC), lactate dehydrogenase (LDH) levels, and patient-reported outcomes on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale scores. The availability of a common reference C5i treatment group in both PEGASUS and APPLY PNH studies allowed anchored ITC (Bucher method). Simulated treatment comparison (STC) assessed the robustness of the main analysis.</p><p><strong>Results: </strong>Overall, baseline characteristics of the populations in the PEGASUS and APPLY PNH studies were broadly comparable. Anchored ITC showed comparable outcomes (mean difference, [95% CI]) on change-from-baseline to end of study for pegcetacoplan versus C5i, and iptacopan versus C5i, respectively, across endpoints: Hb level (-0.49 g/dL [-1.78, 0.80]); ARC (-34.41 × 10<sup>9</sup>/L [-90.02, 21.21]); LDH level (-115.16 U/L [-244.40, 14.01]); FACIT-Fatigue score (3.57 [-5.60, 12.73]). Finally, the STC produced results consistent with the main Bucher analyses across all clinical endpoints and patient-reported fatigue, providing similar point estimates and confidence intervals.</p><p><strong>Conclusion: </strong>This anchored ITC, based on data from pivotal trials, did not indicate significant differences in clinical or patient-reported outcomes between pegcetacoplan and iptacopan in PNH treatment. The findings suggest that PNH treatment decisions should also consider individualised disease- and patient-related factors.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03500549.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Anchored Indirect Treatment Comparison Finds Comparable Effects of Pegcetacoplan and Iptacopan in Paroxysmal Nocturnal Haemoglobinuria.\",\"authors\":\"Regis Peffault de Latour, Austin Kulasekararaj, David Dingli, Koo Wilson, Piotr Wojciechowski, Zalmai Hakimi, Jameel Nazir, Barbara Czech, Peter Hillmen, Jeff Szer\",\"doi\":\"10.1111/ejh.14422\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-rare, acquired non-malignant haematological disorder characterised by thrombosis risk, serious complications and debilitating symptoms in untreated patients.</p><p><strong>Objective: </strong>This anchored indirect treatment comparison (ITC) evaluated efficacy data between proximal complement 3 inhibitor (C3i) pegcetacoplan and factor B inhibitor, iptacopan, in patients with PNH previously treated with complement 5 inhibitors (C5i; eculizumab, ravulizumab).</p><p><strong>Methods: </strong>Respective pivotal studies provided patient-level trial data for pegcetacoplan (16-week PEGASUS [NCT03500549]) and published data for iptacopan (24-week APPLY PNH [NCT04558918]). Differences in study design, duration and statistical methods between PEGASUS and APPLY PNH necessitated the comparative analyses to be conducted on secondary measures based on haemoglobin (Hb) levels, absolute reticulocyte count (ARC), lactate dehydrogenase (LDH) levels, and patient-reported outcomes on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale scores. The availability of a common reference C5i treatment group in both PEGASUS and APPLY PNH studies allowed anchored ITC (Bucher method). Simulated treatment comparison (STC) assessed the robustness of the main analysis.</p><p><strong>Results: </strong>Overall, baseline characteristics of the populations in the PEGASUS and APPLY PNH studies were broadly comparable. Anchored ITC showed comparable outcomes (mean difference, [95% CI]) on change-from-baseline to end of study for pegcetacoplan versus C5i, and iptacopan versus C5i, respectively, across endpoints: Hb level (-0.49 g/dL [-1.78, 0.80]); ARC (-34.41 × 10<sup>9</sup>/L [-90.02, 21.21]); LDH level (-115.16 U/L [-244.40, 14.01]); FACIT-Fatigue score (3.57 [-5.60, 12.73]). Finally, the STC produced results consistent with the main Bucher analyses across all clinical endpoints and patient-reported fatigue, providing similar point estimates and confidence intervals.</p><p><strong>Conclusion: </strong>This anchored ITC, based on data from pivotal trials, did not indicate significant differences in clinical or patient-reported outcomes between pegcetacoplan and iptacopan in PNH treatment. The findings suggest that PNH treatment decisions should also consider individualised disease- and patient-related factors.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03500549.</p>\",\"PeriodicalId\":11955,\"journal\":{\"name\":\"European Journal of Haematology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-04-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Haematology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/ejh.14422\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Haematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/ejh.14422","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Anchored Indirect Treatment Comparison Finds Comparable Effects of Pegcetacoplan and Iptacopan in Paroxysmal Nocturnal Haemoglobinuria.
Background: Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-rare, acquired non-malignant haematological disorder characterised by thrombosis risk, serious complications and debilitating symptoms in untreated patients.
Objective: This anchored indirect treatment comparison (ITC) evaluated efficacy data between proximal complement 3 inhibitor (C3i) pegcetacoplan and factor B inhibitor, iptacopan, in patients with PNH previously treated with complement 5 inhibitors (C5i; eculizumab, ravulizumab).
Methods: Respective pivotal studies provided patient-level trial data for pegcetacoplan (16-week PEGASUS [NCT03500549]) and published data for iptacopan (24-week APPLY PNH [NCT04558918]). Differences in study design, duration and statistical methods between PEGASUS and APPLY PNH necessitated the comparative analyses to be conducted on secondary measures based on haemoglobin (Hb) levels, absolute reticulocyte count (ARC), lactate dehydrogenase (LDH) levels, and patient-reported outcomes on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale scores. The availability of a common reference C5i treatment group in both PEGASUS and APPLY PNH studies allowed anchored ITC (Bucher method). Simulated treatment comparison (STC) assessed the robustness of the main analysis.
Results: Overall, baseline characteristics of the populations in the PEGASUS and APPLY PNH studies were broadly comparable. Anchored ITC showed comparable outcomes (mean difference, [95% CI]) on change-from-baseline to end of study for pegcetacoplan versus C5i, and iptacopan versus C5i, respectively, across endpoints: Hb level (-0.49 g/dL [-1.78, 0.80]); ARC (-34.41 × 109/L [-90.02, 21.21]); LDH level (-115.16 U/L [-244.40, 14.01]); FACIT-Fatigue score (3.57 [-5.60, 12.73]). Finally, the STC produced results consistent with the main Bucher analyses across all clinical endpoints and patient-reported fatigue, providing similar point estimates and confidence intervals.
Conclusion: This anchored ITC, based on data from pivotal trials, did not indicate significant differences in clinical or patient-reported outcomes between pegcetacoplan and iptacopan in PNH treatment. The findings suggest that PNH treatment decisions should also consider individualised disease- and patient-related factors.
期刊介绍：
European Journal of Haematology is an international journal for communication of basic and clinical research in haematology. The journal welcomes manuscripts on molecular, cellular and clinical research on diseases of the blood, vascular and lymphatic tissue, and on basic molecular and cellular research related to normal development and function of the blood, vascular and lymphatic tissue. The journal also welcomes reviews on clinical haematology and basic research, case reports, and clinical pictures.
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