PTC Study Shows Profound Effects of AADC on Caregivers

Caregivers of children with aromatic l-amino acid decarboxylase (AADC) deficiency spend the bulk of their days providing care, with most needing additional help and having to quit their jobs or greatly reduce working hours, according to responses to a questionnaire developed by PTC Therapeutics.

“As with so many rare diseases, there is a tremendous impact endured by a family caring for a child with AADC deficiency,” Kylie O’Keefe, senior vice president of PTC’s global commercial and corporate strategy, said in a press release.

“These insights demonstrate the high unmet need for therapies and the associated benefits a treatment could provide to caregivers and their families,” O’Keefe added.

The results were presented in a poster titled “Caring for an Individual with Aromatic L-amino Acid Decarboxylase (AADC) Deficiency: Analysis of Reported Time for Practical and Emotional Care and Paid/Unpaid Help,” at the virtual International Society for Pharmacoeconomics and Outcomes Research (ISPOR) North America 2021 Conference, running through Thursday.

A rare genetic disorder, AADC deficiency is caused by insufficient activity of the AADC enzyme due to mutations in the DDC gene. This enzymatic deficiency impairs the production of dopamine and serotonin, two key neurotransmitters, or chemical messengers, used by nerve cells to communicate with each other.

Lower levels of dopamine and serotonin trigger a number of symptoms, with varying degrees of severity, that typically appear early in life. These include developmental delay, intellectual disability, movement disorders, muscle weakness, and problems in the autonomic nervous system, which controls functions such as blood pressure, heart and respiratory rates, body temperature, and digestion.

As such, AADC deficiency patients “require substantial lifelong care,” the researchers wrote.

To better understand the burden of caring for a child with ADDC deficiency, PTC developed a questionnaire assessing time spent caring, the need for paid or unpaid help, interactions with healthcare professionals, and the impact of such care on employment.

Questionnaires were completed by 12 primary caregivers (10 parents, one brother, and one aunt), with a mean age of 44 years, who had consented to undergo a qualitative interview.

Results showed that medical care was sought at a mean of 2.5 months after the child presented the first symptoms, and that it took a mean of eight clinicians/experts (range, one to 24) and a mean of 16.5 months to achieve a final diagnosis of AADC deficiency.

In addition, caregivers of children with ADDC deficiency reported spending a mean of 90 hours (range, 56–140 hours) per week providing practical and emotional care for the child, plus a mean of 15 hours (range, 7–33 hours) per week carrying out administrative tasks like planning and attending appointments. This meant that caregivers spent a mean of 15 hours a day and 105 hours per week caring for the child with AADC deficiency.

Most (75%) caregivers reported to have left their jobs or greatly cut their working hours, and 55% needed additional help (paid or unpaid) to care for the AADC deficiency patient.

Unpaid support usually came from the caregiver’s partner, who provided a mean of 37 hours of help a week (range, 8–93 hours), while paid support was provided by a registered nurse or training nursing assistant for a mean 27 hours per week (range, 10–35 hours). The latter was paid out of pocket or provided by the national service.

These results highlight that caregivers “spent almost every waking moment” caring for the child with AADC deficiency, with most having to “stop working or reduce their working hours,” the team wrote.

As such, they emphasize “the importance of considering the caregiver impact when evaluating the burden of disease,” the researchers added.

At the conference, PTC also presented data on the validation of health utilities previously developed by the company for AADC deficiency through a poster titled, “A Discrete Choice Experiment to Derive Health State Utilities for Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency in France.”

Health utilities — cardinal values of health states that may be experienced by patients — can be used to estimate patients’ health-related quality of life and thereby impact of treatments.

These also are used to determine quality-adjusted life-years, a measure of disease burden that is key in assessing a therapy’s cost-effectiveness. It’s also one of the main outcome measures used in funding decision-making by regulators, particularly in countries with publicly funded health care systems, such as France.

An online survey of 1,000 respondents from the general public in France showed that the health utility values increased as the health of a child with AADC deficiency improved, emphasizing the value of treating the condition and the pain and distress associated with its symptoms.

Of note, PTC’s investigational gene therapy for AADC deficiency, PTC-AADC, which resulted in positive findings in three clinical trials, is currently under regulatory review in the European Union and is anticipated to be submitted to regulatory authorities in the U.S this year.