First-line immunosuppressive therapies for acquired hemophilia A: A 25-year cohort experience and network meta-analysis

• Published in: Thrombosis research Vol. 241; p. 109067
• Main Authors: Rungjirajittranon, Tarinee, Suwanawiboon, Bundarika, Nakkinkun, Yupa, Leelakanok, Nattawut, Kaokunakorn, Thanapon, Chinthammitr, Yingyong, Owattanapanich, Weerapat, Ruchutrakool, Theera
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.09.2024
• Subjects: Acquired hemophilia A; Complete remission; Hemophilia A - blood; Hemophilia A - drug therapy; Humans; Immunosuppressive Agents - therapeutic use; Immunosuppressive treatment; Network Meta-Analysis; Relapse; Retrospective Studies; Acquired hemophilia A; Relapse; Complete remission; Immunosuppressive treatment
• ISSN: 0049-3848; 1879-2472; 1879-2472
• DOI: 10.1016/j.thromres.2024.109067

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. •Acquired hemophilia with high-titer inhibitors had a poorer prognosis compared to those with lower titers.•Steroid monotherapy seems to be less efficacious in treatment, especially in patients with high-titer inhibitors.•Using rituximab in front-line immunosuppressive treatments did not improve complete remission and relapse rates when compared to prednisolone and cyclophosphamide treatments.