From the Journals

New recommendations on immune tolerance induction in hemophilia A



New treatment recommendations, released by a panel of nine experts, offer consensus advice on the use of immune tolerance induction (ITI) therapy in patients with hemophilia A with inhibitors.

The recommendations from the Future of Immunotolerance Treatment (FIT) group were authored by a nine-member committee with expertise in the treatment of hemophilia. The authors attended three meetings from 2017-2018 to form a consensus on the use of nonfactor therapies with current inhibitor management strategies.

“The treatment of hemophilia A has evolved and a number of molecules that potentially can be used in the setting of patients with inhibitors have been developed, or are in various phases of development,” wrote Manuel Carcao, MD, of the University of Toronto and colleagues. The report is published in Haemophilia.

The current body of literature is lacking high-quality evidence on the concomitant use of nonfactor treatments, such as emicizumab, and current inhibitor therapies. The recommendations included the panel’s consensus opinions on treatment of inhibitors, with and without the use of nonreplacement therapies. The concurrent use of factor VIII replacement therapy and emicizumab could inhibit bleeding with lower dose immunotolerance strategies, according to the recommendations.

The group hypothesized that increased uptake of lower dose and lower frequency factor VIII ITI treatment strategies could reduce the likelihood of requiring central venous access while retaining a high probability of treatment success.

“In our new algorithm, we have indicated that one option might be to start patients on low-dose ITI with emicizumab regardless of their historical peak inhibitor titre. Patients could then escalate their ITI regimen should their response to low-dose ITI be deemed insufficient,” they wrote.

The experts provided a novel treatment algorithm for immune tolerance induction without emicizumab in addition to a new theoretical strategy with emicizumab.

Other recommendations included that patients with inhibitors should be offered at least one attempt at ITI and that monthly monitoring should be done and ITI dose and frequency should be adjusted based on changes in bleeding phenotype and inhibitor titer.

The authors acknowledged a current limitation is the lack of published evidence pertaining to the concurrent use of emicizumab and factor VIII replacement therapy.

“The FIT group sees the need for properly conducted prospective studies to evaluate the impact of adding emicizumab, and in the future, other nonfactor therapies, into the management of patients with inhibitors,” the experts wrote.

The manuscript was supported by Grifols. The authors reported financial disclosures related to Grifols and other companies.

SOURCE: Carcao M et al. Haemophilia. 2019 Apr 29. doi: 10.1111/hae.13762.

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