A number of predictive factors for the complete eradication of factor VIII (FVIII) inhibitors following immune tolerance induction (ITI) in patients with hemophilia A were identified in a new Italian study.
The results, published in Haemophilia, showed that historical peak inhibitor titers ≤200 BU/mL (P =.033), inhibitor titers ≤5 BU/mL at ITI initiation (P =.001), and peak titers ≤100 BU/mL during ITI (P <.001) were all good predictors of complete response in a multivariate logistic regression model. Missense mutations and small insertions/deletions of the FVIII gene (P =.027) were also useful for predicting complete inhibitor eradication.
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Of the 137 patients with hemophilia A recruited for the study, 91 (66.4%) achieved a complete response. Of those patients, 70 achieved a response in a median of 11 months.
During a median 120-month follow-up after ITI, only 2 of the 70 patients (2.9%) experienced a relapse of inhibitors. The study also found that patients who did not have a bleeding episode (odds ratio [OR], 3.45; 95% CI, 1.4–8.6) or other adverse events (OR, 2.6; 95% CI, 1.3–5.3) during ITI were more likely to achieve a complete response.
“In this real-world cohort of 137 patients, of whom at least two-thirds had one or more of the risk factors previously described to be associated with poor ITI prognosis, there was a complete or partial eradication of high-titer inhibitors in approximately two-thirds of cases,” the study authors summarized. “These outcomes were maintained in the long term, tolerance and thus feasibility of FVIII prophylaxis/treatment being sustained in 96.7% of successful cases.”
The patients in the study were recruited as part of the Italian ITI Registry PROFIT (PROgnosis Factors in Immune Tolerance) between 2005 and 2015, with a final follow-up in 2018. The median age at ITI initiation was 4.8 years (range, 0.5–58.5 years), with 82% of patients aged less than 8 years old at initiation.
One-hundred (73%) patients received recombinant FVIII products during ITI, while the other 37 (27%) received plasma-derived products. The plasma-derived products were mainly used in adult patients. None of the patients received immunomodulatory drugs during ITI treatment.
Di Minno G, Coppola A, Margaglione M, et al. AICE PROFIT Study Group. Predictors of inhibitor eradication by primary immune tolerance induction in severe haemophilia A with high responding inhibitors. Haemophilia. Published online November 2, 2021. doi:10.1111/hae.14431