{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T20:50:06Z","timestamp":1785876606168,"version":"3.56.0"},"reference-count":33,"publisher":"Becaris Publishing Limited","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Comp. Eff. Res."],"abstract":"\n Aim:<\/jats:bold>\n This study aimed to estimate the relative efficacy between garadacimab 200\u00a0mg once monthly (200 QM) and two dosing regimens of lanadelumab (300\u00a0mg once every 2\u00a0weeks [300 Q2W] and 300\u00a0mg once every 4 weeks [300 Q4W]) in adolescent\/adult patients with hereditary angioedema (HAE) using matching-adjusted indirect comparisons (MAICs), in the absence of head-to-head randomized controlled trials.\n Materials & methods:<\/jats:bold>\n Individual patient data were available from the phase II (\n NCT03712228<\/jats:ext-link>\n ) and the phase III VANGUARD (\n NCT04656418<\/jats:ext-link>\n ) trials investigating garadacimab, and published summary-level data from the phase III HELP trial investigating lanadelumab (\n NCT02586805<\/jats:ext-link>\n ). The primary outcome was time-normalized number of HAE attacks. Secondary efficacy outcomes included time-normalized number of HAE attacks requiring on-demand treatment, time-normalized number of moderate and\/or severe HAE attacks, and proportion of attack-free patients. Quality of life (QoL) was also assessed via change from baseline in AE-QoL total score.\n Results:<\/jats:bold>\n Compared with lanadelumab 300 Q2W, garadacimab 200 QM statistically significantly reduced number of moderate and\/or severe HAE attacks (rate ratio [RR]; 95% confidence interval: 0.25; 0.07, 0.84) and improved AE-QoL score (mean difference: -17.38; -33.67, -1.08). Compared with lanadelumab 300 Q4W, garadacimab 200 QM showed statistically significant improvements in all outcomes: HAE attacks (RR: 0.29; 0.13, 0.63), attacks requiring on-demand treatment (RR: 0.29; 0.13, 0.66), moderate and\/or severe HAE attacks (RR: 0.15; 0.05, 0.49), proportion of attack-free patients (hazard ratio: 3.25; 1.45, 7.29), and AE-QoL score (mean difference: -21.29; -37.39, -5.18).\n Conclusion:<\/jats:bold>\n These MAICs showed improved efficacy and QoL with garadacimab compared with lanadelumab across multiple endpoints. These findings demonstrate that garadacimab may provide improved therapeutic benefit compared with lanadelumab in the long-term prophylactic treatment of patients with HAE.\n <\/jats:p>","DOI":"10.57264\/cer-2024-0237","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T11:18:06Z","timestamp":1752146286000},"source":"Crossref","is-referenced-by-count":6,"title":["Matching-adjusted indirect comparison between garadacimab and lanadelumab for the long-term prophylactic treatment of patients with hereditary angioedema"],"prefix":"10.57264","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2988-6506","authenticated-orcid":false,"given":"Sarah","family":"Walsh","sequence":"first","affiliation":[{"name":"EVERSANA\u2122, Burlington, ON L7N 3H8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9829-7791","authenticated-orcid":false,"given":"Anja","family":"Haltner","sequence":"additional","affiliation":[{"name":"EVERSANA\u2122, New York, NY 10018, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4616-8776","authenticated-orcid":false,"given":"Meaghan","family":"Bartlett","sequence":"additional","affiliation":[{"name":"EVERSANA\u2122, Burlington, ON L7N 3H8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sears","sequence":"additional","affiliation":[{"name":"CSL Behring, King of Prussia, PA 19406, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinglei","family":"Li","sequence":"additional","affiliation":[{"name":"CSL Behring, King of Prussia, PA 19406, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maebh","family":"Kelly","sequence":"additional","affiliation":[{"name":"CSL Behring Ltd, Haywards Heath, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Gavata-Steiger","sequence":"additional","affiliation":[{"name":"CSL Behring AG, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Nenci","sequence":"additional","affiliation":[{"name":"CSL Behring AG, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Jacobs","sequence":"additional","affiliation":[{"name":"CSL Behring, King of Prussia, PA 19406, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1259-5422","authenticated-orcid":false,"given":"Ingo","family":"Pragst","sequence":"additional","affiliation":[{"name":"CSL Behring GmbH, Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelanjana","family":"Ray","sequence":"additional","affiliation":[{"name":"CSL Behring, King of Prussia, PA 19406, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1415-8055","authenticated-orcid":false,"given":"Imtiaz A","family":"Samjoo","sequence":"additional","affiliation":[{"name":"EVERSANA\u2122, Burlington, ON L7N 3H8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"36897","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"issue":"14","key":"e_1_3_8_3_2","first-page":"S292","article-title":"Severity of hereditary angioedema, prevalence, and diagnostic considerations","volume":"24","author":"Bernstein J","year":"2018","unstructured":"Bernstein J. Severity of hereditary angioedema, prevalence, and diagnostic considerations. Am. J. Manag. Care 24(Suppl. 14), S292\u2013S298 (2018).","journal-title":"Am. J. Manag. Care"},{"issue":"6","key":"e_1_3_8_4_2","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.anai.2020.02.018","article-title":"Patient-reported burden of hereditary angioedema: findings from a patient survey in the United States","volume":"124","author":"Banerji A","year":"2020","unstructured":"Banerji A, Davis KH, Brown TM Patient-reported burden of hereditary angioedema: findings from a patient survey in the United States. Ann. Allergy Asthma Immunol. 124(6), 600\u2013607 (2020).","journal-title":"Ann. Allergy Asthma Immunol."},{"issue":"1","key":"e_1_3_8_5_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s13023-021-01717-4","article-title":"Clinical characteristics and burden of illness in patients with hereditary angioedema: findings from a multinational patient survey","volume":"16","author":"Mendivil J","year":"2021","unstructured":"Mendivil J, Murphy R, de la Cruz M Clinical characteristics and burden of illness in patients with hereditary angioedema: findings from a multinational patient survey. Orphanet J. Rare Dis. 16(1), 94 (2021).","journal-title":"Orphanet J. Rare Dis."},{"key":"e_1_3_8_6_2","unstructured":"CSL312 (Garadacimab) in the prevention of hereditary angioedema attacks (NCT04656418). Updated 3 August 2022. Available from: https:\/\/ClinicalTrials.gov\/show\/NCT04656418"},{"key":"e_1_3_8_7_2","unstructured":"CSL Behring. Study Report: a multicenter randomized placebo-controlled parallel-arm study to investigate the efficacy pharmacokinetics and safety of CSL312 in subjects with hereditary angioedema. (2022)."},{"issue":"10382","key":"e_1_3_8_8_2","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/S0140-6736(23)00350-1","article-title":"Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial","volume":"401","author":"Craig TJ","year":"2023","unstructured":"Craig TJ, Reshef A, Li HH Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 401(10382), 1079\u20131090 (2023).","journal-title":"Lancet"},{"issue":"4","key":"e_1_3_8_9_2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/joim.20008","article-title":"Targeting factor XIIa for therapeutic interference with hereditary angioedema","volume":"296","author":"Cohn DM","year":"2024","unstructured":"Cohn DM, Renn\u00e9 T. Targeting factor XIIa for therapeutic interference with hereditary angioedema. J. Intern. Med. 296(4), 311\u2013326 (2024).","journal-title":"J. Intern. Med."},{"key":"e_1_3_8_10_2","unstructured":"CSL Behring. Long-term safety and efficacy of CSL 312 (garadacimab) in the prophylactic treatment of hereditary angioedema attacks. Updated 17 October 2022. Available from: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04739059?term=garadacimab&draw=2&rank=2"},{"key":"e_1_3_8_11_2","unstructured":"EMA. Andembry garadacimab EMEA\/H\/C\/006116 Authorisation Details. (2025)."},{"issue":"20","key":"e_1_3_8_12_2","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1001\/jama.2018.16773","article-title":"Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks: a randomized clinical trial","volume":"320","author":"Banerji A","year":"2018","unstructured":"Banerji A, Riedl MA, Bernstein JA Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks: a randomized clinical trial. JAMA 320(20), 2108\u20132121 (2018).","journal-title":"JAMA"},{"key":"e_1_3_8_13_2","unstructured":"European Medicines Agency. Takhzyro (lanadelumab). Product information (2018). Available from: https:\/\/www.ema.europa.eu\/en\/documents\/overview\/takhzyro-epar-medicine-overview_en.pdf"},{"key":"e_1_3_8_14_2","unstructured":"Food and Drug Administration. TAKHZYRO\u00ae (lanadelumab-flyo) injection for subcutaneous use 2023. Available from: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/761090s010lbl.pdf"},{"key":"e_1_3_8_15_2","unstructured":"Government of Canada. Summary Basis of Decision for Takhzyro. Updated 18 February 2019. Available from: https:\/\/hpr-rps.hres.ca\/reg-content\/summary-basis-decision-detailTwo.php?linkID=SBD00420#:\u223c:text=To%20ensure%20safe%20and%20effective acute%20treatment%20of%20HAE%20attacks"},{"key":"e_1_3_8_16_2","unstructured":"TGA. Australian Public Assessment Report for Lanadelumab. Updated March 2020. Available from: https:\/\/www.tga.gov.au\/sites\/default\/files\/auspar-lanadelumab-200304.pdf"},{"key":"e_1_3_8_17_2","unstructured":"Phillippo D Ades T Dias S Palmer S Abrams KR Welton N. NICE DSU technical support document 18: methods for population-adjusted indirect comparisons in submissions to NICE. (2016)."},{"issue":"6","key":"e_1_3_8_18_2","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S0895-4356(97)00049-8","article-title":"The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials","volume":"50","author":"Bucher HC","year":"1997","unstructured":"Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J. Clin. Epidemiol. 50(6), 683\u2013691 (1997).","journal-title":"J. Clin. Epidemiol."},{"issue":"2","key":"e_1_3_8_19_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1177\/0272989X17725740","article-title":"Methods for population-adjusted indirect comparisons in health technology appraisal","volume":"38","author":"Phillippo DM","year":"2018","unstructured":"Phillippo DM, Ades AE, Dias S, Palmer S, Abrams KR, Welton NJ. Methods for population-adjusted indirect comparisons in health technology appraisal. Med. Decision Making 38(2), 200\u2013211 (2018).","journal-title":"Med. Decision Making"},{"issue":"1","key":"e_1_3_8_20_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2046-4053-4-1","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement","volume":"4","author":"Moher D","year":"2015","unstructured":"Moher D, Shamseer L, Clarke M Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst. Rev. 4(1), 1 (2015).","journal-title":"Syst. Rev."},{"key":"e_1_3_8_21_2","doi-asserted-by":"crossref","first-page":"g7647","DOI":"10.1136\/bmj.g7647","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation","volume":"350","author":"Shamseer L","year":"2015","unstructured":"Shamseer L, Moher D, Clarke M Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 350, g7647 (2015).","journal-title":"BMJ"},{"key":"e_1_3_8_22_2","unstructured":"York Uo. Systematic Reviews CRD's guidance for undertaking reviews in health care. (2008)."},{"key":"e_1_3_8_23_2","unstructured":"ClinicalTrials.gov. A study of JNJ-68284528 a chimeric antigen receptor T cell (CAR-T) therapy directed against B-cell maturation antigen (BCMA) in participants with relapsed or refractory multiple myeloma (CARTITUDE-1). Updated 10 March 2020. Available from: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03548207?term=NCT03548207&draw=2&rank=1"},{"key":"e_1_3_8_24_2","unstructured":"CSL Behring. 253590_CSL312_3001_Final_Tables_20220829. (2022)."},{"issue":"10328","key":"e_1_3_8_25_2","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/S0140-6736(21)02225-X","article-title":"Prophylactic use of an anti-activated factor XII monoclonal antibody, garadacimab, for patients with C1-esterase inhibitor-deficient hereditary angioedema: a randomised, double-blind, placebo-controlled, Phase II trial","volume":"399","author":"Craig T","year":"2022","unstructured":"Craig T, Magerl M, Levy DS Prophylactic use of an anti-activated factor XII monoclonal antibody, garadacimab, for patients with C1-esterase inhibitor-deficient hereditary angioedema: a randomised, double-blind, placebo-controlled, Phase II trial. Lancet 399(10328), 945\u2013955 (2022).","journal-title":"Lancet"},{"issue":"10","key":"e_1_3_8_26_2","doi-asserted-by":"crossref","first-page":"935","DOI":"10.2165\/11538370-000000000-00000","article-title":"Comparative effectiveness without head-to-head trials","volume":"28","author":"Signorovitch JE","year":"2010","unstructured":"Signorovitch JE, Wu EQ, Yu AP Comparative effectiveness without head-to-head trials. Pharmacoeconomics 28(10), 935\u2013945 (2010).","journal-title":"Pharmacoeconomics"},{"issue":"25","key":"e_1_3_8_27_2","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1002\/sim.3697","article-title":"Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples","volume":"28","author":"Austin PC","year":"2009","unstructured":"Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat. Med. 28(25), 3083\u20133107 (2009).","journal-title":"Stat. Med."},{"issue":"9","key":"e_1_3_8_28_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v016.i09","article-title":"Object-oriented computation of sandwich estimators","volume":"16","author":"Zeileis A","year":"2006","unstructured":"Zeileis A. Object-oriented computation of sandwich estimators. J. Stat. Software 16(9), 1\u201316 (2006).","journal-title":"J. Stat. Software"},{"issue":"10","key":"e_1_3_8_29_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v011.i10","article-title":"Econometric computing with HC and HAC covariance matrix estimators","volume":"11","author":"Zeileis A","year":"2004","unstructured":"Zeileis A. Econometric computing with HC and HAC covariance matrix estimators. J. Stat. Software 11(10), 1\u201317 (2004).","journal-title":"J. Stat. Software"},{"key":"e_1_3_8_30_2","unstructured":"CADTH. CADTH common drug review clinical review report for lanadelumab (Takhzyro). (2020)."},{"issue":"7","key":"e_1_3_8_31_2","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1111\/all.15214","article-title":"The international WAO\/EAACI guideline for the management of hereditary angioedema\u2014the 2021 revision and update","volume":"77","author":"Maurer M","year":"2022","unstructured":"Maurer M, Magerl M, Betschel S The international WAO\/EAACI guideline for the management of hereditary angioedema\u2014the 2021 revision and update. Allergy 77(7), 1961\u20131990 (2022).","journal-title":"Allergy"},{"issue":"1","key":"e_1_3_8_32_2","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s12955-019-1229-3","article-title":"Angioedema quality of life questionnaire (AE-QoL) \u2013 interpretability and sensitivity to change","volume":"17","author":"Kulthanan K","year":"2019","unstructured":"Kulthanan K, Chularojanamontri L, Rujitharanawong C, Weerasubpong P, Maurer M, Weller K. Angioedema quality of life questionnaire (AE-QoL) \u2013 interpretability and sensitivity to change. Health Qual. Life Outcomes 17(1), 160 (2019).","journal-title":"Health Qual. Life Outcomes"},{"key":"e_1_3_8_33_2","doi-asserted-by":"publisher","DOI":"10.57264\/cer-2022-0188"},{"issue":"1","key":"e_1_3_8_34_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s40268-021-00337-4","article-title":"Indirect comparison of lanadelumab and intravenous C1-INH using data from the HELP and CHANGE studies: bayesian and frequentist analyses","volume":"21","author":"Mendivil JA-O","year":"2021","unstructured":"Mendivil JA-O, Malmen\u00e4s M, Haeussler K, Hunger M, Jain G, Devercelli G. Indirect comparison of lanadelumab and intravenous C1-INH using data from the HELP and CHANGE studies: bayesian and frequentist analyses. Drugs R D 21(1), 113\u2013121 (2021).","journal-title":"Drugs R D"},{"issue":"4","key":"e_1_3_8_35_2","doi-asserted-by":"crossref","first-page":"100166","DOI":"10.1016\/j.jacig.2023.100166","article-title":"Long-term prophylaxis for hereditary angioedema: initial experiences with garadacimab and lanadelumab","volume":"2","author":"Wong JCY","year":"2023","unstructured":"Wong JCY, Chiang V, Lam DLY Long-term prophylaxis for hereditary angioedema: initial experiences with garadacimab and lanadelumab. J. Allergy Clin. Immunol. Glob. 2(4), 100166 (2023).","journal-title":"J. Allergy Clin. Immunol. Glob."}],"container-title":["Journal of Comparative Effectiveness Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/becarispublishing.com\/doi\/pdf\/10.57264\/cer-2024-0237","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T11:18:15Z","timestamp":1752578295000},"score":1,"resource":{"primary":{"URL":"https:\/\/becarispublishing.com\/doi\/10.57264\/cer-2024-0237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":33,"alternative-id":["10.57264\/cer-2024-0237"],"URL":"https:\/\/doi.org\/10.57264\/cer-2024-0237","relation":{},"ISSN":["2042-6305","2042-6313"],"issn-type":[{"value":"2042-6305","type":"print"},{"value":"2042-6313","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,10]]},"article-number":"e240237"}}