A Reality Check of Hemophilia Care: What a Real-World Study Says About the Unmet Needs of People With Hemophilia A or B

Despite advancements and novel therapies, unmet needs persist in hemophilia management, according to an article in the journal Haemophilia. The needs are particularly notable in achieving effective disease control, especially for patients with hemophilia B with antibodies against clotting factor IX that limits effective prophylaxis options.

Allison Wheeler, M.D.

Allison Wheeler, M.D., an attending physician at Seattle’s Children’s Hospital and the Washington Center for Bleeding Disorders, and her co-authors noted patients with hemophilia face a significant burden of disease, which includes compromised joint health, chronic joint pain, reduced physical activity levels and diminished health-related quality of life (HRQoL). Much of the burden can be attributed to musculoskeletal damage from frequent bleeding episodes.

The goal of hemophilia treatments is to prevent bleeding episodes and associated long-term joint damage. Prophylaxis with coagulation factors is recommended by current guidelines, particularly for patients with severe hemophilia, because of demonstrated superiority over episodic (on-demand) treatment in reducing bleeding tendencies and long-term complications. However, costs and socioeconomic circumstances result in many patients resorting to on-demand treatment.

Wheeler and her co-authors highlighted the added complexity to hemophilia management when it comes to therapies. Weekly intravenous injections of coagulation factor replacement have its challenges. It’s a time-intensive practice associated with injection pain. Additionally, the development of antibodies — sometimes called inhibitors — that can neutralize infused factor VIII, the prophylactic treatment for hemophilia A, and factor IX, the prophylactic treatment for hemophilia B. Patients who develop antibodies often have limited treatment options, leading to a higher disease burden and reduced HRQoL

A real-world look

Given the disease burden, the challenges with inhibitors, and the need for better treatment options, there is a need to evaluate real-world data from patients with hemophilia to better understand existing unmet needs and potentially improve healthcare outcomes. Wheeler and her team conducted the explorer6 study, a prospective, noninterventional study across 33 countries that aimed to assess the real-world unmet needs of patients with hemophilia A and hemophilia B, both with and without inhibitors.

For the study, male patients age 12 and older were included if they had severe hemophilia A or hemophilia B, with or without inhibitors. The primary end point was the number of bleeding episodes from enrollment up to a maximum of 115 weeks during routine clinical treatment practice. The bevy of secondary end points examined physical activity levels measured by a wrist-worn physical activity tracker, the number of treated spontaneous bleeding episodes, treated traumatic bleeding episodes, treated joint bleeding episodes and target joint assessment using the Hemophilia Joint Health Score (HJHS) measurements. A target joint was defined as a single joint with at least 3 spontaneous bleeding episodes.

The number of bleeding episodes over the course of the study or annualized bleeding rates were found to be, on average, less frequent for patients with hemophilia A, hemophilia B or hemophilia A with inhibitors receiving prophylaxis treatment compared to on-demand treatment. When comparing annualized bleeding rates by hemophilia type, numerically lower rates were observed among patients with hemophilia A or hemophilia B receiving prophylaxis versus either type of hemophilia with inhibitors. Lastly, annualized bleeding rates were also reported for treated spontaneous, traumatic, joint, and target joint bleeding episodes. Those results show lower rates with prophylaxis compared with on-demand for both types of hemophilia and hemophilia A with inhibitors.

Physical activity levels (light, moderate, and vigorous) were collected using a wrist-worn physical activity tracker for most patients (95.7%), where data was recorded as a mean percentage of awake time. The majority of awake time was measured as light physical activity, and a smaller percentage was measured as moderate to vigorous physical activity. The tracker measured comparable levels of physical activity for prophylaxis and on-demand patients within each group. Among all patients, those with hemophilia B and inhibitors exhibited the lowest levels of measured physical activity. This aligns with the expectation that patients with hemophilia often experience joint pain and reduced physical activity.

Mean and median HJHS total scores were available for 130 (56.3%) patients where 52.4% of patients reported target joints, most commonly in the knee (54.5%), elbow (50.4%) and ankle (37.2%). The mean number of target joints per patient ranged from 1.3 to 2.3 across all groups. Lower HJHS total scores indicate better joint health and the mean and median HJHS total scores were generally lower for patients receiving prophylaxis compared to on-demand treatment for both types of hemophilia and hemophilia A with inhibitors.

The study highlighted that significant unmet needs persist, particularly for patients receiving on-demand treatment and those with inhibitors, especially hemophilia B with inhibitors. Patients receiving on-demand treatment experienced higher bleeding rates and poorer joint health compared to many on prophylaxis.

Wheeler and her co-investigators concluded that “it is evident that unmet needs, in particular the management of bleeding episodes, joint health and physical activity, remain for patients receiving on-demand treatment and patients with inhibitors, and these are even more substantial for those with HBwI [hemophilia B with inhibitors] for whom no efficacious prophylaxis treatment regimen is available."