Delaying immune drugs with Hemlibra boosts survival: Study
Hemophilia A treatment strategy lowers infections
Delaying the start of immunosuppressive treatment in adults diagnosed with acquired hemophilia A who are receiving Hemlibra (emicizumab-kxwh) to prevent bleeding may reduce the risk of infections and extend survival, a clinical study found.
Patients in the Phase 2 study (NCT04188639 received Hemlibra for 12 weeks while immunosuppression was postponed. They were followed for two years to watch for differences in infections and survival compared with an external group of patients who received immediate immunosuppressive treatment.
“[Hemlibra] provides early protection from bleeds in [acquired hemophilia A] but also enables [immunosuppressive treatment] to be postponed until patients are fit to receive it,” the researchers wrote.
The study, “Sustained Survival Benefit of Emicizumab and Postponed Immunosuppression in Acquired Hemophilia A,” was published in Blood Advances. It was funded by Roche, which owns Genentech, the company that markets Hemlibra in the U.S.
Acquired hemophilia A occurs when the body develops self-reactive antibodies against factor VIII (FVIII), a protein needed for the blood to clot. Without it, patients can experience episodes of heavy and prolonged bleeding. Standard treatment involves immunosuppression to eliminate the self-reactive antibodies driving the disease, but this leaves patients at a high risk of developing infections.
Comparing hemophilia A treatment strategies
Hemlibra is designed to mimic the function of FVIII, helping the blood to clot and reducing the frequency of bleeds. Given as an under-the-skin injection, it is approved for use in children and adults with hemophilia A, both with and without neutralizing antibodies (inhibitors) against FVIII.
Final data from the open-label Phase 2 study in Germany and Austria, which involved 47 patients who had not yet received immunosuppressive treatment, showed Hemlibra is effective in acquired hemophilia A.
The researchers compared the outcomes of these patients with those of 101 patients from an earlier study who had received immediate immunosuppressive treatment without Hemlibra. The two groups were matched so that age, sex, health status, and disease severity were similar.
Thirty-six patients who received Hemlibra were alive after two years. Most (81%) were in partial or complete remission (no active bleeds, normal FVIII activity levels, and no FVIII inhibitors in the case of complete remission). Survival was higher than in patients who received immunosuppressants immediately after diagnosis (82% vs. 63%).
Deaths caused by infections were significantly lower in patients treated with Hemlibra (4% vs. 17%). Deaths related to bleeding were rare and similar in both groups, showing that Hemlibra effectively prevented bleeding.
While patients did not receive immunosuppressive treatment for the first 12 weeks of the study, doctors chose when to start and which regimen to use afterward. All treatments were given in an outpatient setting once patients were discharged after eight weeks.
The most common first-line immunosuppressant was rituximab (sold as Rituxan and others), used off label with or without corticosteroids. Of the 16 patients receiving rituximab, most (88%) achieved complete remission in a median of 17 weeks. Corticosteroids alone were used in eight patients, with seven (88%) also reaching complete remission after 25 weeks.
Six of the 12 patients who had not started immunosuppression by week 24 achieved complete remission spontaneously. This translated into an overall 15% of patients entering remission without the need for immunosuppression.
It took longer for patients whose immunosuppression was delayed to achieve complete remission (median 45 weeks vs. 16 weeks). However, a similar proportion of patients did get to that point (76% vs. 66%), “confirming that postponing IST did not compromise its efficacy,” the researchers wrote.
“The 2-year follow-up data … suggests that a strategy of bleed protection with [Hemlibra] and postponed [immunosuppressive treatment] may have contributed to improved [overall survival] compared to historic controls. This observation should be considered when deciding about individual [immunosuppressive treatment] strategies in patients with [acquired hemophilia A],” they wrote.
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