The epidemiology of inhibitors in haemophilia A: a systematic review

Abstract

This paper emphasizes the importance of distinguishing between the prevalence, incidence and cumulative incidence of inhibitors in haemophilia A. Incidence and cumulative incidence data will include patients with transient inhibitors or whose inhibitors have been eliminated by treatment. As these will not be included in prevalence data, prevalence studies will tend to give rise to lower figures than incidence studies. As a result, the most accurate estimates of the true risk of inhibitor development comes from prospective studies of newly diagnosed haemophiliacs who are tested regularly for the presence of inhibitors. This paper reports a systematic review of the best available evidence relating to the epidemiology of inhibitors in haemophilia A. Cohort studies, registry data reporting incidence or prevalence of inhibitors in patients with haemophilia A, and prospective studies of factor VIII (FVIII) in the treatment of previously untreated patients which reported the development of inhibitors as an outcome, were included in the review. The overall prevalence of inhibitors in unselected haemophiliac populations was found to be 5-7%. The cumulative risk of inhibitor development varied (0-39%). Incidence and prevalence were substantially higher in patients with severe haemophilia. Studies of patients using a single plasma-derived FVIII (pdFVIII) preparation reported lower inhibitor incidence than those using multiple pdFVIII preparations or single recombinant FVIII preparations. Incidence data should be used to estimate the likely demand for treatments aimed at eliminating inhibitors, whereas the best estimates of the overall burden to the National Health Service (NHS) of treating bleeding episodes in patients with continuing inhibitors will come from prevalence studies.

How we treat a hemophilia A patient with a factor VIII inhibitor

“…In a cohort of 316 subjects, Gouw et al found that there was no association between the type of product used and inhibitor development. 32 In addition, since the rate of nontransient inhibitor development in prospective trials of new recombinant products was similar to studies using plasmaderived products 33,34 ; and inhibitor formation is rare in previously treated patients who are switched to recombinant products 33,35,36 ; we believe the overall weight of the data suggests that there is no association between the type of fVIII product and inhibitor formation. Thus, we do not consider the risk of inhibitor formation when selecting a fVIII product to use for an individual patient.…”

Current Controversies in the Formation and Treatment of Alloantibodies to Factor VIII in Congenital Hemophilia A

“…Two systematic reviews published in 2003 showed a significantly lower incidence of inhibitor development with the use of single pdFVIII product over a single rFVIII product; these reviews are summarized in Table 3. 15,16 However, after adjusting for study design, study period, testing frequency, and median follow-up, these data lost statistical significance in the second larger review. 16 The above data are largely retrospective, and a multivariate analysis of the studies in the second review showed an overestimation of inhibitor development in the retrospective studies.…”

Prevention of bleeds in hemophilia patients with inhibitors: Emerging data and clinical direction

“…The development of antibodies that inhibit or neutralize factor VIII (FVIII) replacement therapy occurs in as many as 20% to 30% of patients with severe hemophilia A and represents one of the most serious complications of hemophilia [1][2][3]. Inhibitors typically develop in early childhood, within the first 10-20 exposures to FVIII concentrates [2].…”