Efficacy, safety, and immunogenicity of rurioctocog alfa pegol for prophylactic treatment in previously treated patients with severe hemophilia A: a systematic review and meta-analysis of clinical trials

Bendix Samarta Witarto; Visuddho Visuddho; Andro Pramana Witarto; Henry Sutanto; Bayu Satria Wiratama; Citrawati Dyah Kencono Wungu

doi:10.12688/f1000research.73884.3

Efficacy, safety, and immunogenicity of rurioctocog alfa pegol for prophylactic treatment in previously treated patients with severe hemophilia A: a systematic review and meta-analysis of clinical trials

F1000Res. 2021 Oct 15:10:1049. doi: 10.12688/f1000research.73884.3. eCollection 2021.

Authors

Bendix Samarta Witarto¹, Visuddho Visuddho¹, Andro Pramana Witarto¹, Henry Sutanto², Bayu Satria Wiratama^{3

4}, Citrawati Dyah Kencono Wungu^{5

6}

Affiliations

¹ Medical Program, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.
² Department of Physiology and Pharmacology, SUNY Downstate Health Sciences University, Brooklyn, New York, USA.
³ Department of Epidemiology, Biostatistics, and Population Health, Universitas Gadjah Mada, Yogyakarta, Indonesia.
⁴ Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei, Taiwan.
⁵ Department of Physiology and Medical Biochemistry, Universitas Airlangga, Surabaya, Indonesia.
⁶ Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.

Abstract

Background: Patients with severe hemophilia often present with painful joint and soft tissue bleeding which may restrict them from their daily activities. The current standard of care still relies on a regular prophylactic factor VIII (FVIII), which has a high daily treatment burden. Recently, rurioctocog alfa pegol, a third-generation recombinant FVIII with a modification in its polyethylene glycol (PEG) component, has been developed. Several trials have studied this synthetic drug as bleeding prophylaxis in severe hemophilia A. This study aims to evaluate the efficacy, safety, and immunogenicity of rurioctocog alfa pegol for previously treated patients with severe hemophilia A. Methods: This study was conducted in conformity with the PRISMA guidelines. Data were retrieved from PubMed, Scopus, Cochrane Library, Wiley Online Library, and CINAHL (via EBSCOhost). Study qualities were assessed using the Methodological Index for Non-Randomized Studies (MINORS) and Modified Jadad scales. Results: Four studies involving 517 previously treated severe hemophilia A patients were included in this study. The pooled mean of total annualized bleeding rate (ABR) and hemostatic efficacy was 2.59 (95% CI = 2.04-3.14) and 92% (95% CI = 85%-97%), respectively. Only 30 (2.3%) non-serious and one (1.4%) serious adverse events were considered related to rurioctocog alfa pegol treatment. At the end of the studies, no development of FVIII inhibitory antibodies was observed. None of the developed binding antibodies to FVIII, PEG-FVIII, or PEG was correlated to the treatment efficacy and safety. Conclusions: Despite the limited availability of direct comparison studies, our analyses indicate that rurioctocog alfa pegol could serve as a safe and effective alternative for bleeding prophylaxis in previously treated hemophilia A patients. Moreover, it appears to have low immunogenicity, which further increases the safety profile of the drug in such clinical conditions.

Keywords: drug safety; efficacy; hemophilia A; human and medicine; immunogenicity; prophylaxis; rurioctocog alfa pegol.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Factor VIII* / adverse effects
Hemophilia A* / complications
Hemophilia A* / drug therapy
Hemorrhage / drug therapy
Hemorrhage / prevention & control
Humans
Polyethylene Glycols / therapeutic use
Treatment Outcome

Substances

Polyethylene Glycols
BAX 855
Factor VIII

Grants and funding

The author(s) declared that no grants were involved in supporting this work.