Defining the impact of immune tolerance induction on clinically relevant outcomes in a US cohort of severe hemophilia A.

Although the near-term benefit of immune tolerance induction (ITI) for the treatment of people with severe hemophilia A with inhibitor is apparent, the magnitude of the longer-term impact of ITI on clinical outcomes remains undefined. We examined the association between receiving ITI and the success of ITI on clinical outcomes including (1) clinical events, (2) health care use, (3) quality of life/function, (4) socioeconomic status, and (5) death, using the Community Counts (CC) registry of US Hemophilia Treatment Centers between 2013 and 2017. Multivariate logistic regression, negative binomial, and Poisson models were used. Included in this study were 3659 people with severe hemophilia A with median age of 21 years when entering the CC registry. Among 576 participants with inhibitors, 485 had received ITI (84%). ITI was successful in 299 (61.7%) and partially successful or failed in 95 (19.5%) or 91 (18.7%), respectively. Those that received ITI had fewer treated bleeds, less chronic pain, better function, and higher educational attainment than those not receiving ITI. Successful vs partially successful and failed ITI was associated with fewer treated bleeds, less health care use, less chronic pain, better function, and fewer missed days of school or work. Mortality was not associated with ITI, regardless of its success. Those with successful ITI had similar rates of treated bleeds, chronic pain, and health care use as those with no inhibitors. Undergoing ITI, particularly if successful, improved clinical outcomes but not mortality. These findings support decision making regarding initiation of ITI and inform future clinical trials.