Rosanna Sutherby, Pharm.D.

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With the anticipated regulatory approval of novel hemophilia gene therapies, many in the hemophilia community have identified the need for and importance of people with hemophilia to fully participate in a shared decision-making process with healthcare professionals.

In a paper published last June in the journal 

, M.D., co-director of the Hemophilia and Thrombosis Center at the University of Colorado Anschutz Medical Campus, and colleagues describe the efforts made by several members of the hemophilia community to address this need.

The authors describe shared decision-making as a position where “patients, and family members where appropriate, should be actively involved in an individually tailored, two-way discussion with their care provider, with patient preferences and concerns at the forefront.” Facilitating this type of interaction is critical with people with hemophilia who are often lifelong patients.

According to the paper, for people with hemophilia, challenges to shared decision-making can include disparities in health literacy, exposure to inaccurate or contradictory information via various news sources, including social media, and the complexity of gene therapy itself. In addition, direct-to-patient marketing, permissible in some countries, including the United States, may add confusion for some patients. Healthcare professionals on the other side of the interactions can also lack complete understanding of gene therapy or may have a skewed perception of their patients’ actual understanding of gene therapy.

The Council of the Hemophilia Community (CHC) was assembled to fill these informational gaps. The CHC is an interdisciplinary group of experts consisting of independent advisors, healthcare professionals, industry leaders, and patient representatives. The group held three roundtable meetings between November 2020 and May 2021 to understand the components of the patient experience through hemophilia gene therapy and develop a series of questions and answers to be used as a tool for guiding patient-centered discussions between healthcare professionals and their patients.

The CHC categorized five stages of the patient decision-making journey and aligned each question accordingly. These included pre-gene therapy information seeking, pre-gene therapy decision-making, treatment initiations, short-term post-gene therapy follow-up (1 year or less), and long-term post-gene therapy follow-up (longer than 1 year). Questions fell under several categories, including adherence requirements, treatment regimens, treatment predictability, variability, and durability, and the risks versus benefits of the treatment.

The authors cite the strengths of this tool as having a format that is easy to follow and ready for use. A limitation is a higher-than-average reading level for educational materials (10th-11th grade versus 5th- 8th grade levels). However, they note that this resource is intended to be used by healthcare professionals to individualize their discussions with each patient.

In the future, the authors hope that this tool will be updated and revised based on emerging clinical developments and feedback from the community. Although developed with hemophilia issues in mind, Wang and his colleagues comment that this resource could also be used in other diseases with treatment choices.

Articles

The hemophilia organization developed a shared decision-making tool for patients and providers.

Treatment for Hemophilia: Many Decisions, Some Difficult, All Should Be Shared

Anticipated agency approvals of emerging innovative hemophilia treatments are bound to disrupt healthcare organizations and patient care management. The pipeline includes subcutaneously administered coagulation factor replacements, treatments with a longer duration of action and potentially curative gene therapy.

in September 2022, researchers evaluated the perceived impact of up-and-coming hemophilia treatments on healthcare organizations. The study took place in a hemophilia treatment center in Chambery, France. The investigators arranged a multidisciplinary expert group in hemophilia care management consisting of three physicians, three nurses, two pharmacists, one physiotherapist, and one psychologist. Using the multiple criteria decision analysis (MCDA) approach, a tool used to facilitate decision-making when various criteria need to be considered, the researchers used the following seven steps to complete the study: 1) defining the decision problem, 2) selecting and structuring criteria, 3) weighing criteria, 4) measuring performance alternatives, 5) generating a performance score, 6) calculating aggregate scores, and 7) deliberation.

Healthcare professionals in the study answered questions regarding hemophilia treatment innovations and their anticipated impact on their organization. An online software was used to weigh each answer, and aggregate scores were generated. The criteria with the strongest weight were “acceptability for patient/care-giver/association” (weight of 31.4%), “number of emergency or unscheduled consultations” (weight of 20.3%), and “complexity of the innovation choice” (weight of 16.6%).

Innovations were given aggregate scores of 0 to 100, with the highest scores representing low impact on the healthcare organization. The two treatments with the highest aggregate scores were very long-acting recombinant replacement factor (88.8) and subcutaneous recombinant replacement factor (87). Low scores were associated with gene therapy (27.3) and anti-antithrombin RNA (21.9). Acceptability was perceived to be low for these treatments, and the therapy was considered complex and difficult to explain to patients.

Lead author Karen Beny and her colleagues suggest that discoveries made in this study can be used to guide organizational changes in anticipation of emerging hemophilia treatments. They emphasize that this type of sresearch should be repeated in other hemophilia treatment centers. The authors comment, “A better understanding of the nature and strength of the organizational impact of a therapeutic innovation should allow for a better match between therapeutic choice and individual’s health determinants (biological characteristics, family environment, local health system, cultural context, etc.), to understand the most suitable patient support, and to ensure an optimal healthcare pathway, reducing the risk of dropouts.”

Long-acting recombinant replacement factor gets favorable rating from multidisciplinary group. Gene therapy was viewed with some wariness.

Judging Up-and-Coming Hemophilia Treatments

U.S. Department of Health and Human Services

, Hispanic people with asthma are twice as likely to have emergency room visits due to asthma-related events compared with non-Hispanic white individuals. Additionally, Hispanic children are 40% more likely to die from asthma compared with non-Hispanic white children. And children with asthma have a higher rate of asthma exacerbations than adults.

Interventions that include patient and family education can improve health outcomes in people with asthma. 

 have shown that interventions, such as family education, modifying environmental triggers, and home visits led by community health workers, positively affect asthma-related health outcomes. A study published in the 

 in May 2022 sought to determine whether implementing such interventions in a predominantly Hispanic and low-income population in Hidalgo County, Texas, is cost-effective.

The researchers conducted a cost-effectiveness analysis of the Asthma and Healthy Homes Program developed by the Texas A&M Health Science Center to provide families with asthma education, identify and address common household asthma triggers, and create a family action plan. The study compared the cost of the program with the hypothetical savings in healthcare use afforded by changes in asthma symptoms and calculated cost-effectiveness ratios.

Between 2016 and 2019, 349 children and their families from a primarily Hispanic and low-income community received asthma-related educational services through the Texas A&M program as part of this study. The program’s components include identifying asthma signs and symptoms and common triggers; and proper use of asthma medication and dealing with asthma exacerbations. It also focuses on improving the household environment by keeping the home dry, ventilated, and free of pests, contaminants, and hazardous exposures. Trained community health workers visited the participants’ homes to provide asthma-related education.

Cost-effectiveness ratios were calculated for the following outcomes: the number of asthma exacerbations, hospital and emergency room visits, physical and emotional health of the children and the families, and activities of the children and the families.

Program in Hidalgo, Texas, cost less than $250 per family. A study found that the intervention saved each household an average of $36 per day.

Asthma Education Program in a Hispanic Community Proves To Be Cost Effective

Children with nonsevere and severe asthma are more likely to have declining lung function throughout childhood and into adulthood. Yet predictors of which children will experience poor lung function in have not been thoroughly explored or identified

In a study published in August 2022 in the 

Journal of Allergy and Clinical Immunology

 3 pediatric cohort study to discover phenotypic factors that contribute to declining lung function. SARP 3 is an ongoing longitudinal study with the goal of better understanding asthma phenotypic expressions in children and adults with mild to severe asthma.

Children were enrolled between November 2012 and January 2015. The researchers for the current study included participants with an average age of 11.5 years. A total of 111 had severe asthma, and 77 had nonsevere asthma. The researchers measured lung function at baseline and annually. The primary outcome was the absolute 

 in 1 second (FEV1), a standard measure of lung function, at each assessment for up to 6 years. Secondary outcomes included postbronchodilator FEV1 and prebronchodilator FEV1 over forced vital capacity (FVC).

After analyzing the data, the investigators identified several factors as predictors of FEV1 changes over time, including baseline fractional exhaled nitric oxide (FeNO), response to a characterizing dose of intramuscular triamcinolone acetonide, and maximal bronchodilator responsiveness. Other factors were age, obesity, and frequency of exacerbations.

A significant study finding was the association of asthma exacerbation frequency with changes in FEV1 in boys compared with girls. The researchers found that boys who had one to two exacerbations in the previous year lost -20 mL FEV1 at each successive year. Those with three or more exacerbations during the previous year lost -34 mL FEV1 at each successive year. These associations were not present among girls in the study.

The researchers conclude that determinants of lung function in children with severe and non-severe asthma include the triamcinolone-induced difference from baseline FEV1, FeNO, maximum bronchodilator responsiveness, and obesity. They also discovered that a higher incidence of asthma exacerbations is associated with lower lung function in boys.

The authors commented that their findings offer a framework for identifying children with asthma with an increased risk of declining lung function over time.

A longitudinal study aims to identify which children with asthma are more likely to suffer a loss of lung function.

Predicting Loss of Lung Function in Children With Asthma

 in July 2022 found that diabetes and human immunodeficiency virus (HIV) infection increase the risk of hypertension in men with hemophilia. This is of concern in the hemophilia population because both diabetes and hypertension are associated with an increased risk of intracranial bleeding (brain bleeding). Those with hemophilia already have a higher risk of intracranial bleeding, which can be life-threatening even in people without hemophilia.

Researchers from the University of California, San Diego conducted a retrospective study examining the clinical records of 691 men with hemophilia, ages 18 to 79 years, who were seen at hemophilia treatment centers across North America between 2003 and 2014. They were compared with race- and age-matched men in the general population using data from U.S. National Health and Nutrition Examination Surveys (NHANES) and an outpatient clinic at the Veterans Affairs Medical Center in San Diego.

Each cohort was divided into two groups — a group without diabetes, HIV, or hepatitis C infection and another group with diabetes or a history of HIV or hepatitis C infection. 

Researchers found that hypertension was more common among people with hemophilia compared with the general and veteran populations (50% versus 25.5% and 41.2%). Diabetes was less prevalent in the hemophilia group than in the other two groups (7.8% versus 12.6% and 13.7%).

When comparing all the men without diabetes or HIV or hepatitis infection, the investigators found that the group with hemophilia had the highest rate of hypertension (37%), followed by the group of veterans (34%) and the general population (20%). In the groups with diabetes or a history of a viral infection, 57% of men with hemophilia had hypertension, while 77% of veterans and 53% of NHANES participants had high blood pressure.

Although men with hemophilia had the lowest rate of diabetes among the three groups, the researchers discovered that diabetes had the most significant impact on increasing the risk of hypertension. They found that people with hemophilia who had diabetes or a history of HIV had a higher risk of hypertension compared with hemophilia patients who either had no virus infection or were only infected with hepatitis C. The same association was not noted in the groups without hemophilia.

The authors commented that these findings should highlight the need for early hypertension and diabetes screening in people with hemophilia to adequately control these conditions and prevent associated complications and mortality. This is especially important given that new and developing hemophilia treatments the life expectancy of people with hemophilia.

Findings suggest that screening people with hemophilia for diabetes and hypertension might have benefits. 

Diabetes and HIV May Increase Risk of Hypertension in People with Hemophilia

Hemophilia is a hereditary, lifelong, and life-threatening disorder that, until recently, has had no prospective cure. Gene therapy might change that, but the cost has been predicted to be in the millions.

Individuals with hemophilia have a gene mutation that causes a deficiency in one of two factors integral in the blood coagulation pathway. In hemophilia A, factor XIII is missing; in hemophilia B, it’s factor IX. Hallmark symptoms of the disease include excessive bleeding after internal or external trauma. Areas particularly affected are joints, muscles, and soft tissues. In severe cases, bleeding can occur spontaneously.

Current therapy for hemophilia consists of on-demand or prophylactic intravenous infusions of replacement clotting factor to treat or prevent bleeding. Prophylaxis therapy requires several infusions per week, and the cost can range from $300,000 to $776,000 per year.

Recent research on gene therapy introduces the possibility to significantly reduce or eliminate the need for factor replacement therapy. Treatment is designed as a one-time intravenous injection consisting of an adeno-associated virus vector carrying instructions for liver cells to produce deficient coagulation factors.

At least three gene therapies for hemophilia B are currently in late-stage clinical trials, and all have demonstrated at least a 90% reduction in bleeding events and the need for factor replacement. If all goes well, gene therapy can be a potential cure for hemophilia, but the cost has been estimated at $2 to $3 million per patient.

St. Jude Children’s Research Hospital conducted a cost-effectiveness analysis of gene therapy for severe hemophilia B and found that the novel treatment may be more cost-effective than current therapy despite its sky-high price tag. In the analysis, 

 last November, St. Jude used its own hospital’s data to compare the cost and cost effectiveness of gene therapy with on-demand and prophylaxis factor replacement therapy.

Researchers calculated a total per-patient cost of $87,198 for the manufacturing, distribution, and five-year follow-up of gene therapy for severe hemophilia B. Taking into account the cost of lifelong factor replacement therapy, bleeding complications during on-demand treatments, orthopedic surgery, and hospitalizations, the analysis found that a single dose of gene therapy would be more cost-effective than on-demand or prophylaxis factor replacement in 92% of cases.

According to the authors, gene therapy is in a unique position when it comes to cost analysis. 

, from St. Jude Global Pediatric Medicine and lead author of the analysis, said, “Gene therapy is different because unlike other treatment approaches, it is a long-lasting, one-time treatment and may require a big upfront payment, a payment that can make the affordability seem questionable. Our analysis’ importance is that it sheds light on the many factors that could play a role in the decision-making process regarding reimbursement.”

An analysis found that a single dose of gene therapy would be more cost-effective than on-demand or prophylaxis factor replacement in 92% of cases.