Better outcomes seen with early preventive hemophilia A treatment
Results compared between patients who started prophylaxis before age 3, those who started later
People with hemophilia A who start on preventive treatment in the first years of life generally report better health-related quality of life and joint health, a study reports.
“Our results indicate that delayed start of prophylaxis in an older cohort with severe [hemophilia A] can still achieve excellent bleeding control with intermediate-dose intensity, but at the expense of developing arthropathy [joint disease] and reduced [health-related quality of life] compared to a younger cohort on primary prophylaxis,” the researchers wrote in “Impact of timing of prophylaxis commencement, F8 genotype and age on factor consumption and health-related quality of life in patients with severe haemophilia A,” which was published in Haemophilia.
Hemophilia A is caused by mutations in the F8 gene, which provides instructions for making a clotting protein called factor VIII (FVIII). The disease is marked by bleeding that often causes joint problems.
Replacement therapy, a version of FVIII administered to make up for the missing clotting factor, is used for prophylactic, or preventive, care to reduce the risk of bleeds.
In this study, scientists investigated the impact of the type and timing of preventive treatment on bleed rates, joint health, and quality of life. They reported on data from 37 people with severe hemophilia A who were treated at a center in Norway and one in Sweden.
The patients were divided into two groups. The primary prophylaxis group included 15 patients who started regular preventive treatment with a FVIII replacement therapy before age 3 and before developing any substantial joint problems. The other 22 patients were on regular prophylaxis, but started it much later, usually in adulthood.
Age at starting preventive treatments compared
The median age for starting treatment in the primary prophylaxis group was just over a year. In the secondary group the median age was 31. Patients in the primary prophylaxis group were generally younger when they enrolled in the study.
“Due to changes in clinical practice over the last decades, there was a strong correlation between the current age of the patients, and the type of prophylaxis at start,” wrote the researchers, who also noted that most patients in the secondary prophylaxis group were treated at the Norway center. “Even though the goal of treatment at both [centers] was zero bleeds, this was pursued through different dosing intensity regimens,” they said.
Despite these differences, the median annualized bleeding rate was 0 at both centers, meaning most patients weren’t having a clinically relevant bleed in a given year. This suggests “the intensity of prophylaxis may be successfully individualized and lowered in adults without significantly jeopardizing [bleed control],” the researchers wrote.
Joint health was evaluated with the hemophilia joint health score (HJHS), wherein higher values reflect more severe joint disease. The median score was 4 in the primary prophylaxis group and 20 in the secondary prophylaxis group, suggesting those who started prophylaxis later in life generally had more severe joint damage.
“Clearly, our data underlines the importance of starting primary prophylaxis to avoid progressive joint damage,” wrote the researchers, who also noted HJHS values generally reflected markedly worse joint health in the patients in the secondary group who started on prophylactic treatment in late childhood (between ages 3-9), compared with those in the primary prophylaxis group.
“These findings suggest that high treatment intensity cannot compensate for a delayed prophylaxis start regarding the risk of developing arthropathy,” the researchers wrote, adding the small number of patients who started prophylaxis in late childhood made it hard to draw firm conclusions from the data.
Health-related quality of life was generally high among all the participants. Those in the primary prophylaxis group generally had better health-related quality of life scores, however. This finding “further underscores both the influence of age and the value of starting primary prophylaxis,” the researchers wrote.
Analyses of the specific F8 gene mutations these patients carried revealed the presence of 25 null mutations, that is, mutations that prevented FVIII from being produced. Another 13 mutations were identified that allowed some protein to be produced, but at lower levels or with less functionality. Analyses showed no significant differences in treatment patterns or joint health based on mutation type, though this analysis was limited by the small number of patients, the researchers emphasized.
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