Substitution therapy

Abstract

Emicizumab is a bispecific antibody that recognizes FIX(a)/FX, and mimics FVIIIa cofactor activity. Due to its unique characteristics including longer half-life and subcutaneous injectability, treatment for haemophilia A dramatically improved regardless of the presence of FVIII inhibitor. Protection from pathological change in joints, avoidance of inhibitor development and intra-cranial haemorrhage could be expected by introduction of emicizumab in early childhood. Applications in mild/moderate patients should be also considered. Clinical assessment tool should be standardized; however, since there are limitations to conventional ABR-based assessment. Laboratory monitoring is another practical issue due to the mode of action of emicizumab. Chromogenic assays and global assays could be utilized. The other emicizumab-related practical issue is immune tolerance induction for the inhibitor patients, since ITI remains the only effective means to inhibitor eradication. With the recently introduced Atlanta protocol, emicizumab prophylaxis is given in combination with 50-100 IU/kg FVIII three times a week. A single manuscript has been published, and multiple clinical trials are open to address the efficacy of this strategy. Whether the Atlanta protocol will be fully embraced is yet to be seen, but there is widespread consensus about attempts to tolerize every haemophilia A patient with an inhibitor.