Preventive treatment with Hemlibra (emicizumab) improves health-related quality of life (HQRoL) in children with hemophilia A who develop inhibitors, or neutralizing antibodies, against engineered factor VIII (FVIII), an essential blood-clotting protein, a new analysis of a Phase 3 trial shows.
Such Hemlibra therapy also reduces the burden on the children’s caregivers, the analysis found.
The new findings were reported in the study, “Health-related quality of life and caregiver burden of emicizumab in children with haemophilia A and factor VIII inhibitors—Results from the HAVEN 2 study,” published in the journal Haemophilia.
Hemophilia A is caused by absent or faulty FVIII, a group of related proteins essential for the formation of blood clots. FVIII replacement has been a standard prophylactic (preventive) therapy, yet around 30% of patients develop inhibitors against FVIII, which hampers its efficacy.
Clotting agents that can get around these inhibitors, called bypassing agents, are usually used in these patients. However, their efficacy is variable — and they require frequent and prolonged intravenous (into-the-vein) administration. As a result, patients who develop FVIII inhibitors often have worse quality of life compared with those without the inhibitors.
Hemlibra, co-developed by Chugai Pharmaceutical and Genentech, both part of the Roche group, is intended to mimic the activity of FVIII by binding to both factor IX and factor X, other blood-clotting proteins. It is currently approved in the U.S. for adults and children with hemophilia A, with or without FVIII inhibitors.
Previous data from the Japanese Phase 3 study HOHOEMI (JapicCTI‐173710) showed that Hemlibra — when given under the skin every two weeks or once a month — reduced the number of bleeding events in children younger than 12 and without inhibitors.
Another Phase 3 study, HAVEN2 (NCT02795767), evaluated the safety and effectiveness of Hemlibra as a preventive therapy in children of the same age with hemophilia A and FVIII inhibitors.
Those results showed that Hemlibra was effective, regardless of inhibitor status. Weekly dosing led to a low annualized bleeding rate (ABR) of 0.3, with 77% of participants having no treated bleeding events. Results in children treated twice or once a month were similar.
Now, an international team including scientists at Genentech and Roche assessed the impact of preventive therapy with Hemlibra on the HQRoL of children with hemophilia A and their caregivers who participated in HAVEN 2. Notably, this trial was sponsored by Roche, in collaboration with Chugai.
In total, 85 boys younger than 12 were included in this analysis. The vast majority (96.6%) had severe hemophilia A and 72% had undergone immune tolerance induction or ITI. In this procedure, FVIII is given regularly over a period of time so that the body does not react against it.
The children were asked to respond to the Haemophilia-Specific Quality of Life Assessment Instrument for Children and Adolescents Short Form (Haemo-QoL SF II) questionnaire, composed of 35 items assessing nine domains. These included physical health, sports and school, dealing with hemophilia, treatment, and view of self, family, friends, and other people.
In total, 34 patients, ages 8 to 11, completed the questionnaire.
Caregivers were asked to assess their children’s quality of life using the questionnaire Adapted Inhibitor-Specific Quality of Life Assessment with Aspect of Caregiver Burden (Adapted Inhib-QoL).
Both questionnaires were completed before treatment, and at weeks 13, 25, 37, 49 and 57 (just over one year). Additional questionnaires were done every 24 weeks (nearly six months) thereafter. However, technical difficulties at week 57 prevented questionnaire completion and reduced the compliance rates. As such, data from this timepoint were not presented in the analysis.
Scores ranged from zero to 100, where lower scores indicate better HQRoL and less caregiver burden. The number of missed days from school/daycare and hospitalizations also were analyzed.
Results of Haemo-QoL SF II showed that quality of life steadily improved with time. Specifically, at the study’s start (baseline), the mean total score was 30.2 — indicative of moderate impairment. That score was reduced to 23 by week 49.
In turn, physical health scores improved from 27.7 to 12.3 at week 13, and to 10.9 at week 49.
“These improvements in both domain [total and physical health] scores were maintained for up to 1 year of emicizumab [Hemlibra] treatment,” the researchers wrote.
The proportion of children reporting never or rarely feeling pain in their joints increased by 35%, while those reporting “never” or “rare” pain when moving increased by 21.7%. The largest increase was seen among the proportion of children reporting never or rarely feeling pain in their swellings, which jumped by 43.3%.
In addition, the proportion of patients who consider their disease not to be, or rarely to be a burden, increased from 56.7% at baseline to 75% by week 49.
As for caregivers, “dealing with inhibitors” (baseline score of 57.8), “perceived treatment” (43.9) and “family life” (41.9) were the most affected domains.
These three domains, indicative of caregiver burden, were markedly improved by week 49. Indeed, the mean score for “dealing with inhibitors” decreased to 31.1, while “perceived treatment” dropped to 29.1 and “family life” decreased to 13.9.
Similar to the self-reported improvements by patients, physical health also improved, as assessed by caregivers — the score lowered from 34.6 to 24.7 by week 13. Likewise, the total score decreased from 41.3 at baseline to 22.5 by week 13 and 20 —less than half — at week 49.
Yet, “caregivers of children with HA [hemophilia A] can report higher impairments in HRQoL than their child, linked to the emotional stress associated with the disease (such as financial burden, problems with treatment administration or difficulty dealing with the child’s pain),” the scientists wrote.
Next, the team assessed the impact of Hemlibra on school or daycare attendance, and on hospitalization.
At the study’s start, 75.6% (59 children) were enrolled in school or daycare. Within the four weeks prior to the study, children missed a mean of 41% of school/daycare days (range 29-to-53). This percentage was lower at week 49, as 50 of the 60 participants who completed the questionnaire missed 15% of the days (range 6-to-24) they were supposed to attend school or daycare.
Also by week 49, the proportion of children reporting no missed days increased to 78% compared to 39% at baseline.
In the 24 weeks prior to the study, 25 children (28.4%) had been hospitalized. This number decreased to 19 (21.6%) at the final data cut-off.
Overall, the results support the benefits of preventive treatment with Hemlibra in improving HQRoL both among children with hemophilia A and FVIII inhibitors and their caregivers.
“Emicizumab prophylaxis not only offers a highly therapeutic and well-tolerated treatment option, but also one that alleviates the burden of treatment, and may allow children with HA to lead less-restricted social lives, similar to their peers without HA,” the team concluded.
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