Eficácia, efetividade e segurança do emicizumabe no tratamento da hemofilia a: uma revisão sistemática com meta-análise.

Abstract

INTRODUCTION: Hemophilia A (HA) is a rare bleeding disorder due to reduced or complete absence of the clotting activity of the factor VIII (FVIII). Replacement of FVIII to treat (episodic) or prevent (prophylaxis) bleeding is the main therapeutic recommendation for people with HA (PcHA) and a hemorrhagic phenotype. However, up to 30% of these PcHA may develop anti-FVIII alloantibodies (inhibitors), neutralizing the clotting activity of FVIII and requiring by-pass agents (BPA). Emicizumab is a monoclonal antibody recently approved for prophylaxis of both PcHA without or with inhibitors. AIM: To perform a systematic review to evaluate efficacy, effectiveness, and safety of emicizumab as prophylactic therapy for PcHA. METHODOLOGY: The protocol for this systematic review was published on PROSPERO (CRD42021282088) and will be conducted following PRISMA 2020 statement. The electronic bibliographic databases used as search strategy in this systematic review were PubMed, EMBASE, Cochrane Library, LILACS (Latin America and Caribbean Health Science Literature), and Centre for Reviews and Dissemination (CRD). The search strategies were validated by the main publications found manually on Espistemonikos and Google Scholar. No language and no publication period were used as restrictions on the search. The types of studies included are Randomized controlled trials, non-randomized controlled trials, and observational studies (prospective cohort, retrospective cohort, and cross-sectional) that evaluated the use of coagulation factors VIII and emicizumab for the treatment of PcHA. Two independent reviewers selected the articles and extracted the data. Annualized bleeding rates for treated bleeding were evaluated by meta-analysis. The outcomes quality of life, discontinuation, adverse events, development of inhibitors and of anti-drugs anti-bodies were described. Risk of bias assessments were performed for the evaluation of the methodological aspects of the selected publications. RESULTS: Twelve publications were included in this systematic review. The standard mean difference for annualized bleeding rates for treated bleeding in PcHA without inhibitors were -0.6 (IC95%: -1.0 a -0.2); p-valor = 0.0002 and in people with inhibitors were -1,7 (IC95%: -2,4 a -0,9), p-valor < 0,0001. The safety of emicizumab were demonstrated with the low frequency of discontinuation, adverse events, development of inhibitors and anti-drug anti-bodies. The certainty of the evidence regarding the annualized rate of treated bleeding has a very low level of evidence. CONCLUSION: The effectiveness and safety of emicizumab was demonstrated from the studies included in this systematic review. The meta-analyses performed showed the superiority of prophylaxis with emicizumab in reducing the annualized rates of total treated bleeding in PcHA when compared with prophylaxis with FVIII or BPA.