Disease Burden Persists for Hem A Patients in Japan Despite Treatments

Hospitalization rates remain unchanged while patients pay more for medical care

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Despite the increasing use of preventive factor VIII (FVIII) replacement therapy, people living with hemophilia A in Japan still experience a significant disease burden, according to a recent study.

Using information from health records databases, researchers found that while patients have used increasing doses and spent more on medical care with each passing year, hospitalization rates have not changed.

Other serious complications, like bleeding in the skull and blocked blood flow to the heart, were rarely observed.

The findings were detailed in a study, “Burden of congenital hemophilia A requiring treatment in Japan: The HIKOBOSHI study,” published in the journal Research and Practice in Thrombosis and Haemostasis

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Widespread use of prophylactic replacement therapy in recent years

Hemophilia A is caused by a missing or defective FVIII, a clotting protein in the blood.

A mainstay treatment for the bleeding disorder is FVIII replacement therapy, which provides the missing clotting protein either to treat active bleeds, or on a prophylactic basis to prevent them. Examples include Advate and Afstyla, among others.

The widespread adoption of prophylactic replacement therapy along with better general care in recent years has led to fewer bleeds, less joint damage, and a longer lifespan for these patients.

However, hemophilia A patients can still experience marked disease burden, including hospitalizations, medical expenses, and the risk of developing other health complications.

In this study, researchers wanted to learn more about the real-world treatment patterns and disease burden for hemophilia A patients in Japan. The study was funded by Chugai Pharmaceutical, which originally developed Hemlibra (emicizumab), a treatment approved in Japan for hemophilia A.

The researchers examined clinical data of hemophilia A patients included in either of two different Japanese medical records databases through early 2020.

[Hemophilia A patients] still endure a considerable disease burden, encompassing the need for multiple drug prescriptions, outpatient visits, and hospitalizations

The JMDC medical claims database includes information from 7.4 million people gathered since 2005. The Real-World Data (RWD) electronic medical records database includes records from about 20 million people and dates back to 1985.

The analysis included 459 people from JMDC and 229 from RWD who were receiving treatment for hemophilia A. Patients in JMDC had a mean age of 25 years at the time of their first record, and those in RWD had a mean age of 19.2 years.

FVIII activity levels were available for 197 people in the RWD database. About half of the patients (50.3%) had FVIII activity levels (less than 1%) corresponding to severe disease.

Common co-existing conditions across both databases were hepatitis C virus infection, neurological disease, and high blood pressure.

People with hemophilia A, specifically younger patients, are at risk for intracranial hemorrhage, or bleeding inside the skull. This complication associated with hospitalization was reported in 2.6% of patients in JMDC and 4.4% in RWD, and mostly occurred in children.

These rates were lower than historical rates, likely due to increased awareness and preventive treatment in recent years, the researchers noted.

Ischemic heart disease, marked by reduced blood flow to the heart often due to a blood clot, is a particular concern for older hemophilia A patients. Across the two registries, this complication was identified in one patient.

Steady increase in the mean monthly dose of FVIII products

Hemophilia treatments were reported only in the JMDC database. Most hemophilia-related prescriptions (96.1%) were for FVIII replacement therapy.

A steady increase in the mean monthly dose of FVIII products was observed over time, rising from 2,201 international units (IU) in 2005 to 11,377 IUs in 2019.

That finding “can be attributed to the increasingly widespread use of regular FVIII prophylaxis,” the researchers wrote, noting that higher doses and products with an extended half-life have become more favorable in recent years.

Other treatments included activated prothrombin complex concentrate, bypassing agents, and Hemlibra. The use of Hemlibra increased each year since its approval in 2018, with the highest proportion of prescriptions among children up to 9 years of age.

Consistent with the increased use of hemophilia A treatments, patients spent more on medications with each year that passed. The median expense for medications per person increased from $3,806 in 2005 to $106,361 in 2019.

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No change in hospitalization rates

The researchers anticipated that the widespread use of FVIII replacement therapy would reduce the need for doctor’s office visits and hospitalizations associated with bleeding events.

Instead, no overall change in hospitalization rates were observed over time. That could be due to a growing number of elderly people living with hemophilia A who might be admitted to the hospital for other medical reasons, the team noted.

Moreover, while outpatient visits showed an increasing trend until 2012, they have since decreased slightly to 2019. Whether or not clinic visits were related to medication administration wasn’t specified.

Overall, the findings show that despite widespread use of preventive treatments, hemophilia A patients “still endure a considerable disease burden, encompassing the need for multiple drug prescriptions, outpatient visits, and hospitalizations.”

Due to a limited amount of data included in the JMDC and RWD databases, “an appropriate method such as prospective epidemiological studies, including a national registry, is required,” the researchers wrote.