Immune tolerance induction results don’t vary among races, ethnicities

Black, Hispanic hemophilia A patients more likely to develop FVIII inhibitors

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Immune tolerance induction (ITI), a type of treatment that’s designed to eliminate neutralizing antibodies, or inhibitors, against clotting factors for people with hemophilia A, may work just as well across different racial and ethnic groups, a study finds.

The findings don’t “support the hypothesis that ITI response varies according to race or ethnicity,” said the researchers about observations that Black and Hispanic patients are more likely to develop inhibitors that can cause treatments to lose their effectiveness. The study, “Race and ethnicity and the success of immune tolerance induction among people with severe haemophilia A in the United States,” was published in the Haemophilia by two researchers from Emory University School of Medicine, Atlanta.

Hemophilia A occurs when blood fails to clot properly because the factor VIII (FVIII) clotting protein is either faulty or missing. As a result, patients may have excessive bleeding that can happen spontaneously or after trauma or surgery.

Factor replacement therapies can prevent or control bleeding episodes by providing the missing clotting protein. Some patients develop inhibitors against the delivered protein, however, preventing it from working properly.

ITI typically uses gradually increasing doses of a clotting protein to teach a patient’s immune system not to view it as a threat. By doing this, the immune system learns to tolerate the clotting protein and stops making neutralizing antibodies against it.

Black or Hispanic people with hemophilia A are more likely to develop inhibitors against FVIII, leading researchers to review registry data from more than 500 people with hemophilia A, ages 3 years and older, who underwent ITI and developed inhibitors against FVIII at a median age of 2 to see if race or ethnicity might influence the chances of the treatment’s success.

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Starting immune tolerance induction early linked to treatment success

No differences in immune tolerance

More than half (56.9%) the patients were non-Hispanic white, 19.1% were non-Hispanic Black, 18.1% were Hispanic, and 4.5% were Asian. Information about race and ethnicity was missing or coded as other for the remaining patients.

Before starting ITI, most patients had low inhibitor levels, a good indicator the treatment would succeed. More than half (59.8%) had successful ITI, defined as going back to receiving replacement therapy at standard doses.

For 20.8% of the patients, ITI was partially successful, that is, they returned to replacement therapy, but required higher doses for it to work properly. ITI failed for the remaining 19.5%, meaning they required bypassing agents to keep bleeding episodes under control.

The proportion of patients with successful ITI wasn’t significantly different between those who were white (63.7%), Black (56.3%), and Hispanic (59.1%), even after accounting for factors such as age and treatment prognosis.

“The proportion [of patients] with successful ITI was generally comparable across racial and ethnic groups with similar prognosis,” the researchers wrote. “When prognosis levels are comparable, so too is the success of ITI.”

The researchers said a misperception about the likelihood of success of ITI could “influence or weaken” a doctor’s recommendation, but said their “findings may guide future ITI discussions and dispel beliefs of lower success rates among minoritized racial and ethnic groups.”