A retrospective study to describe the incidence of moderate to severe allergic reactions to factor IX in subjects with haemophilia B

Recht, Michael; Pollmann, H.; Tagliaferri, Annarita; Musso, R; Janco, Robert L.; Neuman, W. Richey

doi:10.1111/j.1365-2516.2011.02436.x

Cited by 39 publications

(30 citation statements)

References 10 publications

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“…The registry data reported herein for reformulated nonacog alfa supports the safety of nonacog alfa as reported in previous clinical trials in adults and children [8][9][10] and in a retrospective safety analysis [11]. As can be seen in Table 5, adverse events reported in those studies were similar in type and incidence to those reported in this registry.…”

Section: Discussionsupporting

confidence: 90%

A prospective registry of European haemophilia B patients receiving nonacog alfa, recombinant human factor IX, for usual use

et al. 2011

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Nonacog alfa, a recombinant factor IX (FIX) used for the treatment of haemophilia B, was approved in Europe in 1998. In accordance with European Medicines Agency requirements, a registry study was conducted from 2002 to 2009. A reformulated iso-osmotic version was approved for European use in 2007. This study was conducted to evaluate the safety of nonacog alfa in a usual care setting, and provide clinical trial and postmarketing surveillance data support. This open-label, non-interventional, prospective observational cohort study (registry) comprised 52 sites in nine European countries. Patients with haemophilia B receiving nonacog alfa in either formulation for prevention or treatment were followed on a usual care schedule. A total of 218 patients were enrolled, of whom 66 (30.3%) were <18 years of age. Haemophilia severity was evenly distributed, with baseline FIX activity of <1%, 1-5% and >5% in 33.3%, 36.6% and 30.1% of patients, respectively. One hundred thirty-eight patients received the original formulation alone; 80 switched to or received only the new formulation. There was a low incidence of events of special interest (ESIs), with less-than-expected therapeutic effect in five patients (2.2%), inhibitor development in two (0.9%), thrombosis in one (0.5%) and allergic events in eight (3.7%). These accounted for the majority of the 15 serious AEs reported in six patients. Six patients discontinued because of AEs, primarily related to hypersensitivity. Nonacog alfa was shown to be safe for the treatment of haemophilia B, with a low incidence of serious AEs and ESIs.

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Section: Discussionsupporting

confidence: 90%

A prospective registry of European haemophilia B patients receiving nonacog alfa, recombinant human factor IX, for usual use

et al. 2011

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“…In addition, it is well known that allergic or anaphylactoid reactions often occur concurrently with inhibitor development, although the cause of this comanifestation has not yet been elucidated [34,35]. In a recent retrospective analysis of allergic reactions in patients receiving FIX replacement therapy, seven of 180 patients (3.9%) had a moderate or severe allergic reaction to a FIX replacement product, of whom four also developed FIX inhibitors [36]. Results of our pooled analysis are generally consistent with the literature; inhibitors were reported in five (1.2%) patients, four of whom also exhibited allergic-type manifestations.…”

Section: Discussionmentioning

confidence: 99%

Nonacog alfa

Rendo

Smith

Hsiao-Yu

et al. 2015

Blood Coagulation &Amp; Fibrinolysis

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Nonacog alfa is a recombinant factor IX (FIX) product indicated for treatment and prevention of bleeding episodes in patients with haemophilia B. This posthoc analysis evaluated the safety of nonacog alfa in key clinical studies across 15 years. Data were pooled from six prospective studies that utilized on-demand, prophylactic and preventive nonacog alfa regimens: three open-label, nonrandomized studies that assessed efficacy and safety; a bioequivalence study of original and reformulated nonacog alfa; an open-label, randomized study that compared on-demand and prophylactic treatment; and a noninterventional observational registry study that evaluated safety. Safety assessments included adverse events, serious adverse events (SAEs) and events of special interest. In total, 412 patients received nonacog alfa treatment. Adverse events occurred in 220 patients (53.4%), the most common being pyrexia (n = 63), nasopharyngitis (n = 53) and cough (n = 52). Forty-eight patients (11.7%) experienced treatment-related adverse events; the most common were hypersensitivity (n = 6), urticaria (n = 6), FIX inhibition (n = 5) and pyrexia (n = 4). Seventy-four patients (18.0%) developed SAEs. Thirty-seven events of special interest occurred in 31 (7.5%) patients. Events of special interest included allergic-type manifestations (n = 15), inhibitor development (n = 5), lack of effect (n = 8), red blood cell agglutination in tubing or syringe (n = 7), and thrombogenicity (n = 2). Six patients (1.5%) withdrew due to seven adverse events: hypersensitivity (n = 3), drug eruption, pruritic rash, urticaria and decreased therapeutic response (n = 1 each). Four patients died during the study; no deaths were related to study medication. This pooled safety analysis in haemophilia B patients confirmed the safety of nonacog alfa across various patient populations.

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“…The same studies showed that no adverse effects such as thrombotic events or viral transmission could be related to rFIX administration. Table 3 summarizes the most important published clinical studies on rFIX products 25–27,32,38–41. Only a few studies have specifically compared pdFIX and rFIX concentrates,25,26,35,38,41 confirming the lower recovery rate of recombinant product but documenting their equivalence in terms of efficacy rate.…”

Section: Current Fix Therapiesmentioning

confidence: 97%

Treatment of hemophilia B: focus on recombinant factor IX

Franchini

Frattini²,

Crestani³

et al. 2013

BTT

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Hemophilia B is a recessive X-linked bleeding disorder characterized by deficiency of the coagulation factor IX (FIX). In hemophilia B patients the severity of the bleeding phenotype is related to the degree of the FIX defect. Hemophilia B treatment has improved greatly in the last 20 years with the introduction first of plasma-derived and then of recombinant FIX concentrates. Replacement therapy may be administered through on-demand or prophylaxis regimens, but the latter treatment modality has been shown to be superior in prevention of hemophilic arthropathy and in improvement of patients’ quality of life. The purpose of this narrative review is to summarize the current knowledge on treatment strategies for hemophilia B, focusing on recombinant FIX products either clinically used or in development. There is only one rFIX product that is licensed to treat hemophilia B patients; from the analysis of the literature data presented in this review, the authors conclude that this rFIX product has demonstrated an excellent safety profile and excellent clinical efficacy for halting and preventing bleeds in hemophilia B patients. While prophylaxis has emerged as the best therapeutic strategy for such patients because of its ability to prevent hemophilic arthropathy and to improve patients’ quality of life, the pharmacokinetically tailored dosing of rFIX is another key point when planning hemophilia B treatment, as it allows optimization of the factor concentrate usage. Further clinical studies are needed to better assess the safety and efficacy (ie, the incidence of adverse reactions and inhibitor development) of newer rFIX products.

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A retrospective study to describe the incidence of moderate to severe allergic reactions to factor IX in subjects with haemophilia B

Cited by 39 publications

References 10 publications

A prospective registry of European haemophilia B patients receiving nonacog alfa, recombinant human factor IX, for usual use

A prospective registry of European haemophilia B patients receiving nonacog alfa, recombinant human factor IX, for usual use

Nonacog alfa

Treatment of hemophilia B: focus on recombinant factor IX

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