Safety and efficacy of a plasma‐derived monoclonal purified factor VIII concentrate during 10 years of follow‐up

Abstract

In 1995, AAFACT, a new monoclonal purified factor VIII concentrate (FVIII), derived from human plasma, was introduced in the Netherlands. The monoclonal purification based production process includes a viral inactivation step by solvent/detergent treatment. Products manufactured according to this procedure, for example Hemofil M are used worldwide. The aim of the present study was to assess inhibitor development in a large cohort of previously treated patients (PTPs) who were followed up for 10 years. In addition, efficacy, HIV and hepatitis C virus (HCV) transmission, and allergic reactions were monitored. All 165 patients with severe haemophilia A (FVIII<1%) known at the van Creveldkliniek who ever used AAFACT during the period from October 1995 to September 2005 were included. Two of them were previously untreated patients (PUPs) and two others had <50 exposure days. Data on FVIII consumption, number of exposures, bleedings and hospitalization days were collected from start of AAFACT until last clinical and laboratory evaluation while on this product. At the end of follow-up, 91 patients were still using this plasma-derived FVIII. Median age at start of follow-up was 26 years (range 1-52). None of the patients reported lack of efficacy. Median FVIII consumption per patient during follow-up was 2058 IU kg(-1) bodyweight per year, and median number of exposures was 148 per year. During 1029 patient-years of follow-up, one inhibitor was diagnosed in a previously treated patient PTP. This patient developed high titre inhibitor following surgery for which he, during 1 week, had been treated with continuous infusion with recombinant FVIII. No inhibitor occurred during 68 cases of surgery using continuous infusion with AAFACT. No viral transmissions or other adverse events occurred during 10 years of follow-up; AAFACT appeared to be an effective and safe FVIII product.

Long‐term outcomes from prophylactic or episodic treatment of haemophilia A: A systematic review

“…Ewing and colleagues reported meaningful but non‐statistically significant reductions in nonsurgical hospitalizations among children with inhibitors after switching from episodic treatment to prophylaxis . After a median of 7 years of follow‐up, with 165 patients receiving plasma‐derived FVIII concentrate, Mauser‐Bunschoten and colleagues reported 68 total surgical procedures and a median of 1 hospitalization per patient . For context, a recent health resource utilization analysis of patients with 103 haemophilia reported an average of 6 days of hospital admissions per patient per year and 21 surgical admissions over 2 years (results were not reported by treatment) .…”

Guidelines for the management of hemophilia

“…[] Many studies conducted all over the world indicate that HIV, HBV, and HCV transmission through factor concentrate has been almost completely eliminated. [] This is a result of the implementation of several risk-mitigating steps, which include careful selection of donors and screening of plasma, effective virucidal steps in the manufacturing process, and advances in sensitive diagnostic technologies for detection of various pathogens. [] Recombinant factor concentrates have been adopted over the past two decades, particularly in developed countries.…”

“…These include the non-lipid enveloped viruses and prions, for which diagnosis and elimination methods are still a challenge. [] As new treatments are continually emerging in this rapidly changing field, transfusion-transmitted infections in people with hemophilia are best managed by a specialist.…”

Recombinant factor&nbsp;VIII in the management of hemophilia A: current use and future promise

“…The success of these efforts is demonstrated by the fact that no transmission of HIV, hepatitis C, or other virus has been documented to be associated with any of these modern plasma-derived factor VIII preparations since 1990. This safety record for these products ranks among the best for any pharmaceutical product 15–18…”