Target joint resolution in patients with haemophilia A receiving long‐term prophylaxis with BAY 94‐9027

Abstract

Joint bleeding is a hallmark of haemophilia A, 1 with recurrent bleeds having the potential to cause irreversible joint damage and crippling arthropathy, often limiting daily activities and requiring surgery. 2-4 Target joints are those joints where three or more bleeds occur in a 6-month period 5 and are more prone to chronic damage if not properly treated. Prophylaxis with factor VIII (FVIII) concentrates is the current standard of haemophilia care. Its main aim is to prevent the onset and/or progression of joint damage by reducing the frequency and severity of recurrent bleeding episodes, including that into joints, thus preventing haemarthropathy. 2,3 Reduced bleeding through long-term prophylaxis also improves quality of life and allows patients to participate in physical and social activities. 4,6 Avoiding surgery to treat or replace damaged joints may also contribute to savings in healthcare costs. Despite the availability of effective factor replacement therapy, recurrent joint bleeding remains a clinical challenge, particularly in patients with severe haemophilia A. 2 To optimize outcomes, prophylaxis needs to be started early in life and individualized to meet the clinical and lifestyle needs of each patient. 2,6 This tailoring should take into account patients' bleeding phenotype, joint status, lifestyle, degree of physical activity and pharmacokinetic response to clotting factor concentrates. 3,6 Patient adherence to prophylaxis is also relevant to achieving good outcomes. 6 Despite acceptance of prophylaxis, adherence rates can be low due to the need for frequent dosing. 7 BAY 94-9027 (damoctocog alfa pegol; Jivi ® ; Bayer AG, Germany) is an extended half-life B-domain-deleted, site-specifically PEGylated recombinant FVIII. Due to its prolonged halflife, BAY 94-9027 has the potential to maintain FVIII at a higher haemostatic level for longer periods versus standard-acting agents. 8 This longer half-life also allows less frequent dosing, which in turn could help to improve adherence when used for prophylaxis. 7 This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Turoctocog alfa pegol (N8‐GP) in severe hemophilia A: Long‐term safety and efficacy in previously treated patients of all ages in the pathfinder8 study

“…The mean change in HJHS for all patients was –0.17, indicating that N8‐GP maintained and marginally improved joint health. Maintenance of joint health over time with long‐term prophylaxis is consistent with findings observed with other EHL molecules 17,18,26 …”

“…Maintenance of joint health over time with long-term prophylaxis is consistent with findings observed with other EHL molecules. 17,18,26 Poisson estimate of mean ABR for overall bleeds with N8-GP was 1.10, which was comparable to pathfinder5 (ABR, 1.08), 8 but slightly lower than pathfinder2 (ABR for Q4D prophylaxis, 2.14; ABR for Q7D prophylaxis, 1.31). 6 The trend for reduction in ABR over time between pathfinder2 and pathfinder8 may in part be attributed to the more frequent prophylaxis regimen administered to most patients during pathfinder8, effectively converting patients to a milder bleeding phenotype.…”

Post‐hoc analysis on the long‐term response to fixed‐dose prophylaxis with N8‐GP in patients with haemophilia A

“…This would be consistent with other EHL molecules, whereby joint bleeds and target joints reduced with long-term prophylaxis. 15,16,20 The rate of spontaneous bleeds in pathfinder 5 was lower than traumatic bleeds throughout the course of the trial, which may in part be due to paediatric patients having less joint damage and being more prone to bleeds from injury/trauma than adult patients.…”

Decreased Bleeding Rates in Patients with Hemophilia A Switching from Standard-Half-Life FVIII to BAY 94-9027 Prophylaxis

“…Target joint resolution of patients who were previously treated with FVIII prophylaxis prior to entry to PROTECT VIII has been published elsewhere. 25 Target joints were present in 59 (72%) out of 82 patients, with a mean (SD) number of historic target joints per patient of 1.4 (1.3) for the whole cohort. Out of a total of 122 historic or new target joints, 111 (91%) had resolved by the cut-off date.…”