Treatment outcomes, safety, and characteristics of immune tolerance induction in patients with hemophilia B and inhibitors: a systematic review

TL;DR

This review examines immune tolerance induction in hemophilia B patients with inhibitors, finding varied success rates and significant adverse events.

Contribution

The study systematically reviews ITI outcomes in hemophilia B patients, highlighting the need for standardized protocols.

Findings

ITI success rates in hemophilia B patients ranged from 12.8% to 100%.

Adverse events like allergic reactions and nephrotic syndrome were frequently reported.

Most ITI attempts used plasma-derived FIX with variable dosing.

Abstract

Inhibitor development against factor (F)IX is a serious complication in patients with hemophilia B (HB). Immune tolerance induction (ITI) aims to eliminate these inhibitors, yet variability in outcomes and treatment regimens is significant.

This systematic review synthesizes evidence on the treatment outcomes, safety, and characteristics in ITI among patients with HB and inhibitors.

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we searched PubMed, Embase, Web of Science, and the Cochrane Library for studies of patients with congenital HB receiving ITI.

Eight single-arm studies involving 125 patients with HB (166 ITI attempts) were analyzed. There was significant heterogeneity in the outcome definitions and treatment protocols across studies. The success rate of ITI in patients with HB varied widely from 12.8% to 100%, with single ITI attempts showing success rates between 12.8% and 83.3%. Adverse events included allergic reactions (incidence, 0%-100%), nephrotic syndrome (incidence, 0%-33.3%), and simultaneous occurrences of both (incidence, 0%-15.4%). The median time to achieve successful immune tolerance ranged from 1.0 to 19.3 months. At least 35.9% of ITI attempts involved FIX injections combined with immunosuppressive therapy. Most ITI attempts used plasma-derived FIX, with nearly equal proportions receiving low/medium doses compared with those receiving high doses.

The significant heterogeneity in outcome definitions and ITI protocols complicates the assessment of treatment efficacy. The high incidence of adverse events demands careful management strategies. Standardizing outcome definitions and ITI protocols is crucial to optimize patient management and improve outcomes.

•Patients with hemophilia B (HB) can develop factor (F)IX inhibitors, complicating their treatment.•This review analyzed immune tolerance induction (ITI) outcomes for 125 patients with HB across studies.•ITI success rates in patients with HB vary significantly, with a high incidence of adverse events.•Standardizing outcome definitions and protocols is vital for improving patient care.

Patients with hemophilia B (HB) can develop factor (F)IX inhibitors, complicating their treatment.

This review analyzed immune tolerance induction (ITI) outcomes for 125 patients with HB across studies.

ITI success rates in patients with HB vary significantly, with a high incidence of adverse events.

Standardizing outcome definitions and protocols is vital for improving patient care.

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