The formation of factor VIII (fVIII) inhibitory antibodies is a major complication of hemophilia A. Immune tolerance induction (ITI) is successful in up to 70% of patients. The probability and predictors of inhibitor recurrence following successful ITI are unknown. The study's objectives are to determine the influence of discontinuation and adherence of post-ITI prophylaxis on inhibitor recurrence, and the probability of recurrence following successful ITI.
In this multicenter retrospective cohort study, 84 male patients with Hemophilia A who successfully completed ITI based on local institutional criteria were enrolled. Sixty four subjects with fVIII <2% who were considered tolerant following ITI based on a negative inhibitor titer and normalized recovery level and/or half-life were analyzed. Kaplan-Meier method and logistic regression models were used to estimate the probability of inhibitor recurrence at 1, 3 and 5 years and to determine the association between clinical characteristics, including adherence to post-ITI prophylaxis and inhibitor recurrence.
Sixty four (76%) patients with fVIII level < 2% met criteria for tolerance and were included in the analysis: 45 (70.3%) subjects did not have a recurrent inhibitor titer and 19 (29.7%) had at least one inhibitor titer > 0.6 BU/ml. The probability of recurrent inhibitor at 1 year was 0.17 (95% CI: [0.05, 0.20]); at 3 years was 0.27 (95% CI: [0.2, 0.4]) and 5 years was 0.35 (95% CI: [0.2, 0.5]). Adherence to prophylactic fVIII infusion was found not to be statistically significant associated with inhibitor-free status (p=0.88). However, the odds of inhibitor recurrence were 11.1 and 9.0 higher in patients who received immunosuppression and in those whose recovery level was < 85%, respectively.
ITI is currently the most effective treatment to eradicate fVIII inhibitors, however 5 years after ITI completion, 30-35% of patients will have at least one inhibitor titer > 0.6 BU/ml. A recurrent inhibitor is unlikely after 5 years of ITI. Adherence to post-ITI prophylaxis does not appear to be a major driver of inhibitor recurrence. FVIII recovery level with a cutoff of 85%, and immunosuppression concomitant with ITI were found to be associated with inhibitor recurrence.
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About this Master's Thesis
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|Natural History of Inhibitor Recurrence Following Successful Immune Tolerance Induction ()||2018-08-28 14:39:20 -0400||