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J Thromb Haemost. 2015 Nov;13(11):1980-8. doi: 10.1111/jth.13143. Epub 2015 Oct 20.

Inhibitor recurrence after immune tolerance induction: a multicenter retrospective cohort study.

Author information

1
Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.
2
Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA.
3
Hemophilia and Thrombosis Center and Children's Hospital Colorado, University of Colorado, Aurora, CO, USA.
4
Children's Hospital of Michigan, Detroit, MI, USA.
5
Children's Hospital of Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
6
Phoenix Children's Hospital, Phoenix, AZ, USA.
7
Children's Mercy Hospital, Kansas City, MO, USA.
8
Department of Pediatrics, University of Miami, Miami, FL, USA.
9
Children's National Medical Center, Washington, DC, USA.
10
Department of Medicine, Tulane University, New Orleans, LA, USA.
11
Department of Medicine, University of Pittsburgh Medical Center and Hemophilia Center of Western Pennsylvania, Pittsburgh, PA, USA.
12
Children's Hospital of Philadelphia, Philadelphia, PA, USA.
13
Department of Pediatrics, Emory University, Atlanta, GA, USA.

Abstract

BACKGROUND:

Immune tolerance induction (ITI) in patients with congenital hemophilia A is successful in up to 70%. Although there is growing understanding of predictors of response to ITI, the probability and predictors of inhibitor recurrence after successful ITI are not well understood.

OBJECTIVES:

To determine the association of clinical characteristics, particularly adherence to factor VIII (FVIII) prophylaxis after ITI, with inhibitor recurrence in patients with hemophilia A who were considered tolerant after ITI.

METHODS:

In this multicenter retrospective cohort study, 64 subjects with FVIII level < 2% who were considered successfully tolerant after ITI were analyzed to estimate the cumulative probability of inhibitor recurrence using the Kaplan-Meier method. The association of clinical characteristics with inhibitor recurrence was assessed using logistic regression.

RESULTS:

A recurrent inhibitor titer ≥ 0.6 BU mL(-1) occurred at least once in 19 (29.7%) and more than once in 12 (18.8%). The probability of any recurrent inhibitor at 1 and 5 years was 12.8% and 32.5%, respectively. Having a recurrent inhibitor was associated with having received immune modulation during ITI (odds ratio [OR] 3.8, 95% confidence interval [CI] 1.2-22.4) and FVIII recovery of < 85% at the end of ITI (OR 2.6, 95% CI 1.3-5.9) but was not associated with adherence to post-ITI prophylactic FVIII infusion (OR 0.5, 95% CI 0.06-4.3).

CONCLUSIONS:

The use of immune modulation therapy during ITI and lower FVIII recovery at the end of ITI appear to be associated with an increased risk of inhibitor recurrence after successful ITI. Adherence to post-ITI prophylactic FVIII infusions is not a major determinant of recurrence.

KEYWORDS:

hemophilia; immune tolerance; incidence; prophylaxis; recurrence

PMID:
26382916
PMCID:
PMC4639409
DOI:
10.1111/jth.13143
[Indexed for MEDLINE]
Free PMC Article

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