Recombinant coagulation factor VIII ( Sino Cell Technologies)

Patients with hemophilia who have recurrent hemarthroses develop hemophilic arthropathy (HA). Regular prophylaxis with factor (F) VIII (FVIII) can reduce HA, but there is a need for objective outcome measures to evaluate treatment efficacy.

Evaluate and assess collagen turnover biomarkers in patients with hemophilia A to determine the efficacy of rurioctocog alfa pegol treatment and understand their potential as tools for guiding treatment decisions and monitoring outcomes.

Joint remodeling was assessed by analyzing serum levels of collagen remodeling products at baseline and months 3, 6, 9, and 12 in a 98 patient subset receiving pharmacokinetics-guided prophylaxis with rurioctocog alfa pegol, targeting FVIII trough levels of 1 to 3 International Units (IU)/dL or 8 to 12 IU/dL (PROPEL study, NCT0285960).

Basement membrane metabolism-related type 4 collagen remodeling products (C4M and PRO-C4) decreased after 3 months at all time points by up to 25% at 1 to 3 IU/dL (P = .049, P < .0001) and 8 to 12 IU/dL FVIII trough levels (P = .0002, P < .0001). Interstitial tissue metabolism-related type 3 (C3M) and 5 (PRO-C5) collagen remodeling products decreased after 3 months, by up to 19% at 1 to 3 IU/dL FVIII trough level (P = .0001, P = .009) and 23% at 8 to 12 IU/dL FVIII trough level (P = .0002, P = .001). An increase of up to 12% was seen for cartilage metabolism-related type 2 collagen product (PRO-C2, not C2M) after 6 months at both trough levels (P = .01, P = .005). When stratified by prior treatment, changes in C3M (P = .03) and C4M (P = .02) levels were observed between trough levels for prior on-demand treatment but not for prophylaxis prior to study entry.

Joint improvement measured by collagen remodeling biomarkers specific to the basement membrane, interstitial matrix, and cartilage was seen with pharmacokinetics-guided prophylaxis. These collagen remodeling biomarkers warrant further exploration as biomarkers to guide treatment toward improvement in HA.

To report the long-term prophylaxis management of a child with type 3 von Willebrand disease by switching to Wilate (Octapharma AG), a plasma-derived, double virus-inactivated concentrate of freeze-dried of a 1 to 1 ratio of active Von Willebrand Factor and Factor VIII (pdVWF:pdFVIII) recently marketed as Eqwilate in France.

This is a case report of 12.6-year-old boy with congenital Type 3 VWD who had a history of frequent bleeds. Prophylaxis started at the age of 38 months with FVIII-poor pdVWF concentrate (Wilfactin, LFB) and FVIII (Wilstart, LFB). Pharmacokinetics and thrombin generation assay were performed. Annualized bleeding rate was derived from the bleeding episodes documented in the medical record during a 24-month period before and after starting pdVWF:pdFVIII concentrate.

Both product injections promptly raised the endogenous thrombin potential (ETP). However, the maximal concentration of formed thrombin was higher following pdVWF:pdFVIII injection. Due to a high bleeds frequency and better results regarding FVIII levels and thrombin generation, the prophylaxis regimen was changed to the same dose and frequency of pdVWF:pdFVIII concentrate (42 IU/kg per day, three times a week). During the last 24 months, annualized total, trauma, and spontaneous bleeding rates were 7.5, 4.5, and 3, respectively. These rates decreased to 2, 1.5, and 0.5 respectively during the next two years. The mother reported a marked improvement in the quality of life of his son and hers.

Switch to pdVWF:pdFVIII concentrate for long-term prophylaxis in a young type 3 VWD patient was safe and effective in reducing bleeds.