A new study has investigated the effects of up-titration of the prophylactic emicizumab dose in patients with hemophilia A whose bleeding was not well controlled. The study, published in Haemophilia, found that up-titration of the dose to 3 mg/kg once a week improved bleeding control and was well tolerated among a small cohort of patients.

“Despite the demonstrated consistent pharmacokinetic (PK) and pharmacodynamic (PD) behavior across age and body weight strata, emicizumab dose adaptation might be beneficial for some individuals,” the authors wrote. “The present analysis investigated the effect of emicizumab dose up-titration on PK, PD, efficacy and safety in [people with hemophilia A] whose bleeding control was suboptimal in phase III/IIIb clinical studies.”

The research team evaluated 675 children and adults with hemophilia A, with or without factor VIII inhibitors, from 7 clinical studies who were receiving prophylactic emicizumab. Twenty-four patients were considered eligible for dose up-titration due to suboptimal bleeding control, which was defined as 2 or more spontaneous and clinically significant bleeds in the last 12 or 24 weeks despite treatment with emicizumab.


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Outcome measures included bleeding events, adverse events, drug-related adverse events, serious adverse events, and injection site reactions. Serum emicizumab concentration, thrombin generation, and antidrug antibody levels were monitored in the patients.

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The results showed that the dose up-titration was effective in improving bleeding control in most cases, and the weekly dose of 3 mg/kg was well tolerated. There was no evidence of increased prothrombotic risk. The authors caution that this study had no control group, and the small number of participants whose emicizumab was up-titrated limits the ability to draw firm conclusions.

However, the results obtained suggest that further larger and well controlled studies on higher doses of emicizumab for some patients with hemophilia A are warranted.

Reference

Schmitt C, Mancuso ME, Chang T, et al. Emicizumab dose up-titration in case of suboptimal bleeding control in people with haemophilia A. Haemophilia. Published online October 21, 2022. doi:10.1111/hae.14679