Early initiation of prophylaxis regimens and joint status monitoring over time are the most relevant aspects of evaluating treatment efficacy in this patient population, study authors concluded.
For patients with severe hemophilia A, starting prophylaxis with coagulating factor VIII (FVIII) early on was associated with long-term joint status preservation in a study published in Research and Practice in Thrombosis and Haemostasis.
Prophylactic FVIII concentrate has long been the standard treatment for severe hemophilia A, but the long-term effects of primary prophylaxis on joint involvement are not clear, according to the study authors. To characterize the level of joint protection in patients with severe hemophilia A receiving prophylactic FVIII over time, the retrospective study analyzed data from patients at La Paz University Hospital in Madrid, Spain, after 20 years of follow-up.
“Given the proposed definition of prophylaxis recently published in the World Federation of Hemophilia guidelines, which prioritizes outcomes over product regimens, there is a need for reliable, homogeneous data on the achievements of classical primary prophylaxis regimens with FVIII and their long-term outcomes to establish the goals for treating these patients,” the authors wrote.
A total of 60 patients who did not develop FVIII-neutralizing inhibitors were included in the analysis. Four additional patients were excluded because they developed inhibitors early in treatment and required changes to their prophylactic treatment during follow-up. The median follow-up length was 10 years among the 60 patients included in the cohort, and the mean (SD) age at the end of follow-up was 10.7 (5.5) years. The mean (SD) length of follow-up for prophylaxis was 113 (6) months.
At the end of the follow-up period, 23.3% of patients (n = 14) had joint involvement. Among those patients, the median age at prophylaxis initiation was 3 years, and the median age at the onset of joint involvement was 12 years. In patients who did not show joint involvement, the median age at prophylaxis initiation was 1 year.
Adherence to treatment was similar between the groups, but patients who did not develop joint involvement had a median (IQR) annual joint bleeding rate of 0 (0-0.2) compared with 0.2 (0.1-0.5) in patients who developed joint involvement. Trough FVIII levels were also lower in those without joint involvement. Additionally, a higher percentage of patients without joint involvement were physically active compared with patients who had joint involvement (70% vs 50%, respectively).
Starting prophylaxis at 2 years or younger was correlated with joint protection in the overall study cohort. Among patients who did not have joint involvement, a delay in treatment initiation was associated with higher rates of total bleeds, joint bleeds, and higher trough FVIII levels.
Overall, the study found that the main factor associated with joint preservation over time in patients with severe hemophilia A was starting primary prophylaxis at a younger age. While early initiation has been found more effective by other studies, the authors noted that there has been variation regarding the age of initiation and follow-up lengths.
They also emphasize the importance of individualizing treatment according to each patient’s bleeding phenotype.
“In our series, lower FVIII trough levels in patients without joint involvement did not result in an increase in total bleeding events. In patients who developed joint involvement, median FVIII trough levels greater than 1% were not associated with decreased annual joint bleeding rates,” the authors wrote. “These data highlight the importance of individualization according to the patient’s bleeding phenotype vs the conventional need to maintain certain target FVIII trough levels during follow-up.”
Study limitations included its retrospective nature and the potential inaccuracy of patient-reported bleed and joint bleed data, the authors noted.
The authors concluded that early initiation of prophylaxis regimens—preferably when children are younger than 2 years—and joint status monitoring over time are the most relevant aspects of evaluating treatment efficacy in this patient population. The authors note that while the treatment algorithm may change given the increased use of novel, non–factor-replacement therapies, these long-term data on factor replacement are still important.
“While we await the results of long-term prophylaxis using the new non-replacement therapies, our data illustrate the importance of starting treatment early and serve as a basis for establishing a solid long-term comparison of the specific variables that influence the treatment of these patients,” the authors concluded.
Meijón Ortigueira MDM, Álvarez-Roman MT, De la Corte-Rodriguez H, Butta Coll N, Jiménez-Yuste V. Long-term impact of primary prophylaxis on joint status in patients with severe hemophilia A. Res Pract Thromb Haemost. 2023;7(1):1-9. doi:10.1016/j.rpth.2022.100005