Switching clotting factor products doesn’t lead to new inhibitors

Switching clotting factor products did not cause new inhibitors (neutralizing antibodies that can prevent the treatment from working) to develop in previously treated patients with moderate or severe hemophilia A or B who had no detectable inhibitors at the time of switching.

That’s according to data from ATHN 2 (NCT02546622), a clinical study sponsored by the American Thrombosis and Hemostasis Network that aimed to assess the rate of inhibitor development in patients who were planning to switch or who had recently switched clotting factor products.

The findings from the study, “Lack of Inhibitor Development in Previously Treated People With Haemophilia Switching Factor Products—Final Results of Athn 2: Factor Switching Study,” were described in a letter to the editor in the journal Haemophilia by a team of researchers across the U.S.

Hemophilia is caused by a lack of certain clotting factors, proteins that normally help form blood clots that prevent excessive bleeding. In hemophilia A, the missing clotting factor is factor VIII (FVIII), while in hemophilia B, it is factor IX (FIX). The standard treatment for preventing bleeding is factor replacement therapy, which supplies patients with a working version of the clotting factor they are missing.

However, the immune system may recognize the delivered clotting factor as a threat and start producing antibodies, called inhibitors, against it, potentially making treatment less effective or ineffective. Inhibitors are especially common in patients with severe hemophilia who have never received hemophilia treatment. They often develop within 50 days of receiving a clotting factor product.

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No inhibitors

ATHN 2 was designed to determine whether switching from one brand of clotting factor concentrate to another could cause inhibitors to develop in previously treated patients with hemophilia. The study involved 292 patients, ranging in age from six months to 78, who planned to start receiving a new replacement treatment within 60 days of enrolling or who had switched products during the previous 50 weeks (nearly one year).

Of the 292 patients, 164 had enough data to determine whether an inhibitor developed within one year or 50 days of treatment exposure, whichever came first, after the switch. Of these, 132 had hemophilia A and 32 had hemophilia B.

Results showed that none of the 164 patients developed a new inhibitor after switching clotting factor products. Those who had previously had inhibitors did not lose their immune tolerance or develop inhibitors again.

Because the study included all approved factor replacement treatments available at the time, it reduced the chance that the findings were affected by limited treatment choices. However, it had some limitations. Missing data meant that only 164 of the 292 patients could be evaluated for inhibitor development. In addition, the COVID-19 pandemic disrupted follow-up visits for some patients.

Still, ATHN 2 found no evidence that switching clotting factor products caused new inhibitors to arise in previously treated patients with moderate or severe hemophilia A or B who had no inhibitors when they switched.

“This lack of inhibitor development was consistent between people with a previous history of an inhibitor and those without such a history,” the researchers wrote.