Emicizumab dose capping in obese patients with Haemophilia A: Early outcomes at a single centre

Abstract

During phase 3 clinical trials and since its commercialization, emicizumab (Hemlibra), a bispecific monoclonal antibody acting as a substitute for activated coagulation factor VIII (FVIII), has proven effective for bleeding prevention in persons with haemophilia A (PwHA) with and without inhibitors. It is administered subcutaneously, requires less frequent injections compared to intravenously administered factor replacement products and thereby reduces the treatment burden. 1 For all these reasons, emicizumab is a potentially life-changing treatment option for PwHA, especially those with inhibitors. Safety concerns include thrombotic microangiopathy and thrombosis after concomitant use of activated prothrombin complex concentrate (aPCC) and occurrence of anti-drug antibodies (ADA). 1 Emicizumab can be administered following different maintenance dosing regimens, after a loading dose of 3 mg/kg once a week during 4 weeks: 1.5 mg/kg once weekly (Q1W), 3 mg/kg every 2 weeks (Q2W) or 6 mg/kg every 4 weeks (Q4W). After the loading dose period, plasma concentrations of emicizumab will remain stable over time, in contrast to conventional factor replacement products, whose pharmacokinetics are marked by peaks and troughs. The total body weight-based dosing scheme currently used in clinical trials and clinical practice, and which applies to paediatric and adult patients with or without inhibitors, is supported by population pharmacokinetic analysis. 2,3 However, little is known about emicizumab dosing strategies in obese patients (i.e., individuals with a BMI greater than 30 kg/m 2 as per the WHO definition 4 ).Considering that the prevalence of overweight and obesity in PwH is approaching that of the general population, 5 this is an important issue.The impact of obesity on pharmacokinetics and usage of coagulation factor concentrate has been previously discussed in the literature 5,6 and adds to other potential problems associated with obesity in PwH such as cardiovascular disease and musculoskeletal and psychological health.

Building a haemophilia‐specific navigator in Epic® Electronic Health Records: Single‐centre preliminary experience

“…The haemophilia flowsheet however incites clinicians to investigate whether any new haemophilia patients have been born in the family or if there are any potential haemophilia carriers who have not yet been screened. We are presently using this feature in our recruitment process for an ongoing carrier screening project 21. Certain functionalities of Epic have been adapted to haemophilia patient care in our HTC, without being part of the haemophilia navigator as such.…”