Immunogenicity, efficacy and safety of Nuwiq® (human-cl rhFVIII) in previously untreated patients with severe haemophilia A-Interim results from the NuProtect Study.

INTRODUCTION: Nuwiq® (Human-cl rhFVIII) is a fourth generation recombinant FVIII, produced in a human cell line, without chemical modification or protein fusion. No inhibitors developed in studies with Nuwiq® in 201 previously treated patients with haemophilia A (HA). The immunogenicity, efficacy and safety of Nuwiq® in previously untreated patients (PUPs) with severe HA are being assessed in the ongoing NuProtect study. METHODS: The study, conducted across 38 centres worldwide, is evaluating 110 true PUPs of all ages and ethnicities enrolled for study up to 100 exposure days (EDs) or 5 years maximum. The primary objective is to assess the immunogenicity of Nuwiq® (inhibitor activity ≥0.6 BU) using the Nijmegen-modified Bethesda assay at a central laboratory. RESULTS: Data for 66 PUPs with ≥20 EDs from a preplanned interim analysis were analysed. High-titre (HT) inhibitors developed in 8 of 66 patients after a median of 11.5 EDs (range 6-24). Five patients developed low-titre inhibitors (4 transient). The cumulative incidence (95% confidence interval) was 12.8% (4.5%, 21.2%) for HT inhibitors and 20.8% (10.7%, 31.0%) for all inhibitors. During inhibitor-free periods, median annualized bleeding rates during prophylaxis were 0 for spontaneous bleeds and 2.40 for all bleeds. Efficacy was rated as "excellent" or "good" in treating 91.8% of bleeds. Efficacy of surgical prophylaxis was "excellent" or "good" for 8 (89%) procedures and "moderate" for 1 (11%). No tolerability concerns were evident. CONCLUSION: These interim data show a cumulative incidence of 12.8% for HT inhibitors and convincing efficacy and tolerability in PUPs treated with Nuwiq® .

Disability in Indian patients with haemophilia.

Chronic shortage of clotting factor concentrates, exorbitant treatment costs and the poor economic status of patients makes disability an inevitable consequence of haemophilia in India. The prevalence and risk factors for disability were studied in 148 patients with severe haemophilia A registered at five haemophilia clinics in the country. Disability was measured using a scoring method that used a compilation of functional ability, mobility and range-of-motion scores for each patient. Patients ranged in age from 5 to 55 years. Only nine of 148 patients were free of disability. The proportion of disability free patients in the 5-12, 13-24 and 25+ age groups were 14.3%, 4.4% and 0% respectively. The risk factors significantly associated with disability were patients age, socio-economic status, number of persons in the family, family history of haemophilia, frequency of physiotherapy exercises, home use of coagulation factor concentrate and type of blood product(s) used, that is clotting factor concentrate or cryoprecipitate. The study highlights the need to provide coagulation factor concentrates in sufficient amounts to prevent disability, the beneficial role of physiotherapy exercises and the advantage of older patients as peer educators for younger patients. The most important utility of the data is to demonstrate the widespread prevalence of disability amongst patients, its social costs in terms of incomplete education and unemployment, which justifies the need to include haemophilia as one of the conditions under the Disability Act of India.