Use of Emicizumab in Patients with Hemophilia a with and without Inhibitors: A Single Center Experience

Abstract Emicizumab is a humanized bispecific recombinant monoclonal antibody that binds the enzyme factor IXa and the substrate factor X and mimics the function of FVIII. It solved some unmet needs of haemophilia A (HA) treatment, such as regimen (once weekly up to once monthly infusion) and route of administration (subcutaneous). Most importantly, emicizumab reduce bleeding episodes and improved the quality of life of these patients. Emicizumab received FDA approval for prophylaxis in HA patients with inhibitors in November 2017 and for patients without inhibitors in October 2018.The aim of this study is to provide information on treatment with emicizumab in patients with severe haemophilia A with and without inhibitors in terms of efficacy, safety and quality of life. Here we report our experience with 9 patients with severe haemophilia A (5 with inhibitors and 4 without inhibitors) that were switched from replacement therapy to emicizumab prophylaxis. Median age at initiation of treatment was 26.8 years for patients with inhibitors and 18.7 years for those without inhibitors. Median duration of therapy was 12 months for patients with inhibitors and 8 months for those without inhibitors. All patients were started on emicizumab with a loading dose of 3 mg/kg once weekly for 4 weeks followed by a maintenance dose of 1.5 mg/kg once weekly or every two weeks. The mean annual bleeding rates (ABR) in patients without inhibitor prior to emicizumab was 1.5 compared to 0 while on emicizumab prophylaxis. In subjects with inhibitors ABR was 1.8 compared to 0.4 while on emicizumab prophylaxis. Furthermore, no adverse events including thrombotic events occurred in course of emicizumab prophylaxis. Bleeding events in course of emicizumab prophylaxis did not request any treatment with replacement therapy or bypassing agents. The questionnaire evaluating quality of life (HAL v 2.0 - 2015 ITA; pedHAL v 2.0 - 2015 ITA) was administered to the patients before switch to emicizumab and after a follow up of six months. The scores showed a significant improvement in terms of quality of life in course of emicizumab prophylaxis. In conclusion, our experience suggests that emicizumab prophylaxis is safe and improved protection against bleeding and quality of life compared to replacement therapy in patients with severe A haemophilia. Disclosures Di Raimondo: Amgen: Honoraria; Jazz Pharmaceutical: Honoraria; Pfizer: Honoraria; Janssen Pharmaceuticals: Honoraria; Bristol Myers Squibb: Honoraria; AbbVie: Honoraria.

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Lifelong prophylaxis in a large cohort of adult patients with severe haemophilia: a beneficial effect on orthopaedic outcome and quality of life

European Journal Of Haematology ◽

10.1111/j.1600-0609.2012.01750.x ◽

2012 ◽

Vol 88 (4) ◽

pp. 329-335 ◽

Cited By ~ 59

Author(s):

Mohammed Khawaji ◽

Jan Astermark ◽

Erik Berntorp

Keyword(s):

Quality Of Life ◽

Beneficial Effect ◽

Large Cohort ◽

Adult Patients ◽

Haemophilia A ◽

Severe Haemophilia

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RESULTS FROM A 52-WEEK, NONINTERVENTIONAL STUDY OF BRAZILIAN INDIVIDUALS WITH SEVERE HAEMOPHILIA A RECEIVING PROPHYLAXIS: RATES OF BLEEDING, FVIII USE, AND QUALITY OF LIFE

Hematology Transfusion and Cell Therapy ◽

10.1016/j.htct.2021.10.393 ◽

2021 ◽

Vol 43 ◽

pp. S232-S233

Author(s):

GG Yamaguti-Hayakawa ◽

PR Villaça ◽

C Lorenzato ◽

MH Cerqueira ◽

LCO Oliveira ◽

...

Keyword(s):

Quality Of Life ◽

Haemophilia A ◽

Severe Haemophilia ◽

Noninterventional Study

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Measuring the impact of changing from standard half‐life (SHL) to extended half‐life (EHL) FVIII prophylaxis on health‐related quality of life (HRQoL) in boys with moderate/severe haemophilia A: Lessons learned with the CHO‐KLAT tool

Haemophilia ◽

10.1111/hae.13905 ◽

2019 ◽

Vol 26 (1) ◽

pp. 73-78 ◽

Cited By ~ 1

Author(s):

Manuel Carcao ◽

Laura Zunino ◽

Nancy L. Young ◽

Saunya Dover ◽

Vanessa Bouskill ◽

...

Keyword(s):

Quality Of Life ◽

Half Life ◽

Lessons Learned ◽

Haemophilia A ◽

Severe Haemophilia ◽

Health Related Quality ◽

Related Quality ◽

Health Related ◽

The Impact

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Physical fitness, functional ability and quality of life in children with severe haemophilia: a pilot study

Haemophilia ◽

10.1111/j.1365-2516.2006.01307.x ◽

2006 ◽

Vol 12 (5) ◽

pp. 494-499 ◽

Cited By ~ 33

Author(s):

J. VAN DER NET ◽

R. C. VOS ◽

R. H. H. ENGELBERT ◽

M. H. VAN DEN BERG ◽

P. J. M. HELDERS ◽

...

Keyword(s):

Quality Of Life ◽

Pilot Study ◽

Physical Fitness ◽

Functional Ability ◽

Haemophilia A ◽

Severe Haemophilia

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Physical function and quality of life in adolescents with haemophilia (SO-FIT study)

The Journal of Haemophilia Practice ◽

10.17225/jhp.00018 ◽

2013 ◽

Vol 1 (2) ◽

pp. 11-14 ◽

Cited By ~ 3

Author(s):

Kate Khair ◽

Melanie Bladen ◽

Michael Holland

Keyword(s):

Quality Of Life ◽

Clinical Practice ◽

Functional Outcome ◽

Physical Function ◽

Mobile Devices ◽

Haemophilia A ◽

Severe Haemophilia ◽

Quality Of Life Measures

Abstract Introduction: Self-completed measures of physical function and quality of life are increasingly being used in clinical practice yet little is known about how these measures correlate with joint scores in boys with severe haemophilia. In addition, it is not known whether currently used measures of functional outcome correlate with quality of life measures, which measure of physical function is most accurate and whether these measures are acceptable to a well treated contemporary cohort of boys. Methods: The Study Of physical Function In adolescenTs with haemophilia (SO-FIT) is a multicenter, randomized cross-over study designed to answer these questions, and to determine whether these self-reported measures are completed more fully and frequently if made available on mobile devices rather than with conventional pen and paper questionnaires. The study is being run by haemophilia nurse specialists and physiotherapists in UK haemophilia centres and will recruit 120 boys with severe haemophilia A or B, with or without inhibitors aged 8-16 years. Results:The SO-FIT study is now underway, and is expected to complete by the end of 2014.

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Analysis of Bleeding Phenotype of Severe Hemophilia a Carriers and Comparation with a Working Population Group. Impact on Quality of Life

Blood ◽

10.1182/blood.v124.21.5053.5053 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5053-5053

Author(s):

María Eva Mingot-Castellano ◽

María Jose Ariza-Corbo ◽

Álvaro Amo Vázquez de la Torre ◽

María Inmaculada Alonso-Calderón ◽

Pedro Valdivielso ◽

...

Keyword(s):

Quality Of Life ◽

Social Activity ◽

Point Of View ◽

Control Group ◽

Haemophilia A ◽

Bleeding Tendency ◽

Severe Haemophilia ◽

Primary Hemostasis ◽

The Mean

Abstract INTRODUCTION: We have little information about if there is a particular bleeding phenotype of severe haemophilia A female carriers. In the literature, an increased bleeding tendency is described in this group, justified even by levels of factor VIII (FVIII) very close to normal values, in absens of primary hemostasis evaluation in many cases. There is no published evidence about quality of life (QoL) of these women and the relationship between QoL and this bleeding tendency. OBJECTIVES: • To evalute the hemorrhagic phenotype of severe haemophilia A carrier and to compare them with the general population. • To identify symptomatic carriers and to study from laboratory point of view the reasons for that bleeding tendency. • To define the bleeding profile of symptomatic carriers. • To analyze the quality of life and state of anxiety/depression in carriers and to compare them with the general population. PATIENTS AND METHODS: This is a descriptive cross-sectional, non-interventional, single center study. Ethics Committee evaluation and written informed consent are requested to be included for carriers and controls. The target population are severe Haemophilia A carriers from our area aged between 18 and 70 years old. The control group are women from regular health laboral checkings. We will evaluate family bleeding, ischemic and thrombotic personal and familiar antecedents, bleeding profile (ISTH/SSC bleeding assessment tool, ISTH BAT, and pictorial blood assessment chart, PBAC), carrier genetic study, complete blood count, basic biochemistry, haemostasis (aPTT, PT, fibrinogen, platelet function tests, FVIIIc, FvWAg and FvWRCo, FXIII). QoL has been studied trough SF-36 (Spanish version 1,4 1999) and anxiety and depression states using Goldberg questionary (1998, Spanish version Gzempp, 1993).The controls have been studied in the same way except for laboratory studies of hemostasis. Only in controls with pathological ISTH BAT (greater than 3) basic and primary hemostasis have been studied. RESULTS: Out of a total of 81 carriers identified between August 2012 to December 2013. We have evaluated 69 carriers. To achieve a confidence level of 95% with 50% heterogeneity we have recruited 138 controls. The mean and standard deviation (SD) age of the carrier and controls was 43.7+/-15 and 41.5+/-11.7 years old (p 0.308). In the population of carriers, the mean and SD of FVIII levels are 87.2+/-35.7%. We found no relationship between levels of FVIII:c and haemophilia genetic defect (34.8% substitutions, 34.8% intron 22, 27.5% mutations). 20.3% of carriers and 2.2% of controls present a pathologic ISTH BAT score (p 0.001). There are 14 carriers with a pathologic ISTH BAT score (median 5.5, range 4-11). In this group we found FVIII levels less than 40% in 4 carriers, 1 thrombopathy and levels of VWF:RCo and VWF:Ag compatible with von Willebrand disease in other 4 carriers. The remaining 5 present ISTH BAT score between 4 and 6 (low), FVIII levels above 60% and no other laboratory abnormal results to justify bleeding tendency. In the 3 controls with pathologic ISTH BAT score (4-5), we have not found any hemostatic disorder from laboratory point of view. The carrier group has a higher incidence of abnormal bleeding at wounds (1.5% vs. 14.5% p 0.000), tooth extraction (3.6% vs. 11.6%, p 0.028), surgery (0% vs. 11.6 %, p 0.028) and methrorragia (13.8% vs 43.5%, p 0.000). However when methrorrragia is analysed with an objective scale of menstrual bleeding as PBAC, methrorragia incidence in carriers is similar to controls (23.2% carriers vs 31.5% controls, p 0.071). Regarding quality of life, the population of carriers presented worse scores in the domains of social activity (p 0.01) and mental health (p 0.014). In the group of symptomatic carriers there are no differences in quality of life with the control group. The control population has a higher incidence of anxiety (42.3% vs 21.7%, p 0.002), with no differences in the presence of depression. CONCLUSIONS: In our series, women with symptomatic severe hemophilia A are those with FVIII lower than 40% or another disorder of hemostasis associated to carrier condition. The hemorrhagic symtoms able to define a severe haemophilia A carrier could be abnormal bleedings from wounds (surgical or traumatic) and in dental extractions. Quality of life in women with hemophilia is worse in the mental health and social activity fields, but for reasons other than their own bleeding phenotype. Disclosures No relevant conflicts of interest to declare.

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