Long‐term outcome of haemophilia A patients after successful immune tolerance induction therapy using a single plasma‐derived FVIII/VWF product: the long‐term ITI study

Abstract

Introduction: Immune tolerance induction (ITI) is a standard intervention to eradicate inhibitors in haemophilic patients. However, information on the long-term condition of patients who eradicated the inhibitor totally or partially after ITI is scarce. Aim: To perform a long-term follow-up to describe the status of patients reported as ITI success in the G-ITI study. Methods: This was an international, multicentre, observational, retrospective study of the 57 haemophilic patients who were reported as ITI success in the G-ITI study. Demographics and post-ITI clinical data recorded until January 2015 were extracted from the medical records. A descriptive analysis was undertaken. Results: Forty-four patients were evaluable. Post-ITI follow-up was 9.1 years in average. Thirtyseven target joints were affected in 21 patients; 38 patients presented bleeding with a mean of 1.0 AE 1.2 episodes year À1, most of them (271/330) treated with Fanhdi â (Grifols). Around half of the patients underwent at least one surgical procedure. Most venous access complications were of expected nature, requiring hospital stay in practically all cases. Fanhdi was used in 42 patients as the regular haemophilia treatment after ITI, mainly prophylactically. Three patients (6.8%) who were being treated with Fanhdi (prophylaxis), Kogenate (prophylaxis) and Emoclot (on demand), respectively, showed inhibitor relapse (at 29, 53 and 13 months after ITI, with 0.9, 3.65 and 12.5 BU respectively). All of them were successfully tolerized after rescue ITI. Conclusion: After ITI success, all patients continued with regular successful FVIII treatment for haemophilia for more than 9 years. The few inhibitor relapses were successfully overcome after rescue ITI.

The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab

“…The FIT group (now 12 years later) concurs with DiMichele et al that historical pre‐ITI peak inhibitor titre and peak inhibitor titre while on ITI are independent predictors of ITI success/failure, but we no longer believe that the inhibitor titre immediately prior to starting ITI on its own is an independent predictor of ITI success/failure given some recent publications and unpublished experiences of FIT group members of starting ITI in patients with HTI without waiting for titres to fall. Other putative prognostic factors, also mentioned for risk stratification by several authors, we regard (much like DiMichele et al did) as being less important …”

Long‐term outcomes from prophylactic or episodic treatment of haemophilia A: A systematic review

“…There is limited information on the effect of prophylaxis on hospitalizations and surgeries (Table ). Jiménez‐Yuste and colleagues conducted a long‐term follow‐up study of 44 patients who had eradicated inhibitors after receiving immune tolerance induction (ITI) therapy . During a median 9 years of follow‐up, there were 79 hospitalizations and 39 surgical/invasive procedures.…”

Recombinant factor VIII Fc fusion protein for immune tolerance induction in patients with severe haemophilia A with inhibitors—A retrospective analysis

“…Eradication of inhibitors using ITI is the gold standard for patients with HTI in haemophilia A and is the only therapy that can allow the patient to return to a prophylactic FVIII regimen. Studies have shown that long‐term outcomes, including mortality, are greatly improved if inhibitors are eradicated and, furthermore, the long‐term costs associated with inhibitor therapy would likely be reduced by early eradication …”