Long-Term Safety and Efficacy Data of a Plasma-Derived Factor VIII Concentrate with von Willebrand Factor for Treatment of Patients with Hemophilia A Covering 18 Years

Abstract

We describe the results of the (to our knowledge) longest long-term noninterventional study so far performed to obtain real-life data on the treatment of hemophilia A patients with a single plasma-derived FVIII concentrate containing von Willebrand factor (pdFVIII; Haemoctin/Faktor VIII SDH Intersero). A total of 198 patients (146 in Germany and 52 in Hungary), of whom 160 had severe and 38 nonsevere hemophilia A, representing all age groups (0–88 years; mean ∼25 years at inclusion) were analyzed during prophylactic or on-demand treatment over 18 years (overall 1,418 patient-years; mean >7 years). pdFVIII was very effective and well tolerated. The mean annual bleeding rate, including spontaneous and traumatic bleeds, was considerably lower for patients treated prophylactically (mean 5.4; median 3.1) than for patients treated on demand (mean 26.1; median 21.9). Inhibitors were found in 13% (3/23) and high-titer inhibitors in 4% (1/23) of previously untreated patients with severe hemophilia A. Four previously treated patients with severe hemophilia A developed inhibitors, thereof three high-titer inhibitors (3.3 and 2.5 high-titer inhibitors in 1,000 patient-years). No unexpected adverse effect on the health of the patients, no pdFVIII-related thrombosis, thromboembolic event, or hypersensitivity reaction, and no suspected viral transmission related to pdFVIII were documented.

Long‐term analysis of the benefit of prophylaxis for adult patients with severe or moderate haemophilia A

“…Therefore, these data cannot be compared directly with treatment data from (randomized) clinical trials. 32 However, median ABR under continuous prophylaxis in the present study (1.3) was comparable with that observed in clinical trials with other FVIII products (median 0.0-2.0) with observation periods of about 6 months. 20,[27][28][29]40…”

“…9,[13][14][15][16][17][18][19][20][21][22][23][24][25][26]34 This prospective study is the longest NIS of a single FVIII concentrate reported so far in which treatment data were collected from the routine treatment of HA patients. 32 In a broad range of patients with severe as well as non-severe HA, covering all age groups up to 88 years, long-term prophylaxis with a pdFVIII concentrate reduced the ABR remarkably, in some cases down to zero.…”

“…5,30,37 Treatment peaks due to recurring joint bleeding and severe bleeding episodes were identified as risk factors for inhibitor development in both previously treated and untreated patients treated on demand with pdFVIII. 32 Therefore, more long-term data should be acquired under real-life conditions, to establish the best prophylactic regimen based on dose, frequency and the minimum effective dose. 7,31,38 These data, which the present report may contribute to, will help to improve HA therapy and the quality of life of patients with HA.…”

“…Final safety analyses have been published elsewhere. 32 The analyses presented in the following were performed with all 198 patients from one NIS (with an uniform data format).…”

“…The present prospective long‐term, non‐interventional study (NIS) has been conducted under real‐life conditions to investigate the influence of prophylactic FVIII treatment or the switch to this regimen on the ABR of HA patients of all age groups and HA severities, and the long‐term effects of this regimen on the patients’ ABRs. Final safety analyses have been published elsewhere 32 . The analyses presented in the following were performed with all 198 patients from one NIS (with an uniform data format).…”