Motor Function, Breathing Important in Choosing Treatment

Improvement in motor function, breathing, and ease of administration are among the factors that people with spinal muscular atrophy (SMA) and their caregivers value most when deciding on available treatments, a new study reports.

The study, “Treatment preference among patients with spinal muscular atrophy (SMA): a discrete choice experiment,” was published in the Orphanet Journal of Rare Diseases. It was funded by Genentech (a member of the Roche Group).

Over the past five years, three disease-modifying therapies for SMA — Biogen’s Spinraza (nusinersen), Roche’s Evrysdi (risdiplam), and Novartis’s Zolgensma (onasemnogene abeparvovec-xioi) — have been approved in the U.S. As more treatments for the condition are approved, patients, as well as their caregivers and healthcare providers, must make choices about which treatment options to pursue.

“Little focus has been given to understand how patients and caregivers weigh the possible risks associated with therapies against potential benefits associated with those therapies,” wrote the researchers.

In order to better understand how these choices are made, the researchers conducted a discrete choice experiment survey. In this type of survey respondents are asked to choose between sets of two hypothetical medications; for example, respondents might be asked to pick between a therapy that has a good safety profile and poor efficacy, or a highly effective therapy with a high risk of side effects. By analyzing the different choices made, researchers can ascertain which aspects of therapies are most important to the respondents.

The survey was completed by 101 people — 65 self-reporting people with SMA, and 36 caregivers of SMA patients. The patients ranged in age from less than 1 year old to 67; 64% were female, and 81% were white. There were 21 patients with type 1 SMA, 48 patients with type 2, 29 patients with type 3, and one patient with type 4. The SMA type for two patients was classified as “unknown.”

Among the patients, 59 were being treated with Spinraza, and 10 had received Zolgensma.

Overall, the survey respondents placed great value on whether a potential therapy would improve or stabilize their motor and breathing functions. This was “not surprising,” according to the researchers.

Ease of administration also was valued. Oral therapies, and therapies given via a one-time infusion, were preferred mostly over therapies given by repeated intrathecal injections (injections directly into the spinal canal). Generally, oral treatments were preferred.

Most of those surveyed responded negatively toward hypothetical therapies that are approved to treat only very young patients (younger than 2), and toward therapies that carried serious or life-threatening safety risks.

Compared to findings from a previous study — done when there were no approved SMA treatments — respondents in this survey were generally less willing to pick therapies with a high safety risk, even if the hypothetical benefit was greater.

Findings were mostly consistent across different subgroups among the respondents. However, improved breathing function was considered more important than improved motor function by those with type 1 or type 2 SMA, whereas for those with type 3, motor function was valued more highly than breathing function.

“Findings from this study identified the overall preferred treatment attributes including improvement in motor function, breathing function, oral administration, broad indication without age limits, and minimal risk. Overall, the preference on treatment characteristics were quite robust across demographic groups and clinical subgroups,” the researchers wrote.

“These findings can inform the perceptions and preferences of SMA patients and their caregivers to stakeholders including regulators, patients, patient advocacy group such as CureSMA, and providers,” they added.

The researchers highlighted several limitations to this study, including the fact that the respondents — who were recruited through CureSMA — represent “a highly informed and engaged patient population,” so the results might not be reflective of all people with SMA in the U.S. They also noted that all of the data was self-reported, raising the possibility of errors.

Also, cost and affordability of treatments were not included in the survey. The researchers also emphasized that treatment decisions are always more complicated than the comparatively simple and hypothetical scenarios posed in the survey. They stressed that individual decisions about treatment need to be made in the context of each individual patient, and that such decisions require collaborative decision-making among patients, caregivers, and their healthcare team.

“Nonetheless, these hypothetical scenarios provide insight into patient and caregiver preferences that can inform future drug development and drive the implications for future research of this highly rare, complicated, and expensive disease,” the researchers wrote.