{"title":"First-line immunosuppressive therapies for acquired hemophilia A: A 25-year cohort experience and network meta-analysis","authors":"Tarinee Rungjirajittranon , Bundarika Suwanawiboon , Yupa Nakkinkun , Nattawut Leelakanok , Thanapon Kaokunakorn , Yingyong Chinthammitr , Weerapat Owattanapanich , Theera Ruchutrakool","doi":"10.1016/j.thromres.2024.109067","DOIUrl":null,"url":null,"abstract":"<div><p>Acquired hemophilia A (AHA) presents a significant bleeding risk. Management involves bleeding control and immunosuppressive therapy (IST) to eliminate inhibitors. This study, encompassing a retrospective cohort of 76 newly diagnosed AHA patients (1997–2022), evaluated IST outcomes such as complete remission (CR), relapse, and mortality rates, alongside influencing factors. Supplementing these findings, a systematic review and network meta-analysis compared CR and relapse rates across ISTs, sourcing from Embase, Scopus, and ScienceDirect up to November 2023. In our cohort, demarcated by a 20 Bethesda-unit titer threshold, cyclophosphamide plus prednisolone (CP; <em>n</em> = 64) was the predominant initial IST. Lower inhibitor levels significantly correlated with higher CR rates (86.8 % vs 62.2 %; <em>P</em> = .014) and showed an odds ratio of 0.26 for CR (<em>P</em> = .021). Median relapse-free survival (RFS) extended to 37.13 months, significantly enhanced by CP (hazard ratio, 0.24; 95 % confidence interval, 0.10–0.60; <em>P</em> = .002). Our network meta-analysis, including 1476 CR and 636 relapse patients, indicated CP and rituximab-based ISTs significantly outperformed steroid monotherapy in terms of CR and lower relapse rates (risk differences of 0.15 and −0.13/−0.15, respectively; <em>P</em> < .05), without significant differences between CP and rituximab. Moreover, adding rituximab to the front-line treatment did not produce superior outcomes compared to the CP regimen alone, positioning CP as a viable first-line choice, particularly where rituximab is less accessible. The consideration of IST toxicity remains critical in treatment decisions.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0049384824001993/pdfft?md5=cfbe630a305ad16dc73c6c8439ab32fd&pid=1-s2.0-S0049384824001993-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Thrombosis research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0049384824001993","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Acquired hemophilia A (AHA) presents a significant bleeding risk. Management involves bleeding control and immunosuppressive therapy (IST) to eliminate inhibitors. This study, encompassing a retrospective cohort of 76 newly diagnosed AHA patients (1997–2022), evaluated IST outcomes such as complete remission (CR), relapse, and mortality rates, alongside influencing factors. Supplementing these findings, a systematic review and network meta-analysis compared CR and relapse rates across ISTs, sourcing from Embase, Scopus, and ScienceDirect up to November 2023. In our cohort, demarcated by a 20 Bethesda-unit titer threshold, cyclophosphamide plus prednisolone (CP; n = 64) was the predominant initial IST. Lower inhibitor levels significantly correlated with higher CR rates (86.8 % vs 62.2 %; P = .014) and showed an odds ratio of 0.26 for CR (P = .021). Median relapse-free survival (RFS) extended to 37.13 months, significantly enhanced by CP (hazard ratio, 0.24; 95 % confidence interval, 0.10–0.60; P = .002). Our network meta-analysis, including 1476 CR and 636 relapse patients, indicated CP and rituximab-based ISTs significantly outperformed steroid monotherapy in terms of CR and lower relapse rates (risk differences of 0.15 and −0.13/−0.15, respectively; P < .05), without significant differences between CP and rituximab. Moreover, adding rituximab to the front-line treatment did not produce superior outcomes compared to the CP regimen alone, positioning CP as a viable first-line choice, particularly where rituximab is less accessible. The consideration of IST toxicity remains critical in treatment decisions.
期刊介绍:
Thrombosis Research is an international journal dedicated to the swift dissemination of new information on thrombosis, hemostasis, and vascular biology, aimed at advancing both science and clinical care. The journal publishes peer-reviewed original research, reviews, editorials, opinions, and critiques, covering both basic and clinical studies. Priority is given to research that promises novel approaches in the diagnosis, therapy, prognosis, and prevention of thrombotic and hemorrhagic diseases.