Spinraza (nusinersen) improves muscle strength, endurance, and independence in adults with spinal muscular atrophy (SMA), meeting most of their positive expectations, a small, real-world study in Germany has shown.
The data also showed that patients reported greater improvements than those observed with objective motor function measures, suggesting that patient-reported outcome measures may be more sensitive to motor improvements in this adult patient population.
The study, “Treatment expectations and patient-reported outcomes of nusinersen therapy in adult spinal muscular atrophy,” was published in the Journal of Neurology.
Since its approval was based on clinical trials of infants and young children with SMA, data on Spinraza’s effectiveness in older children and adults rely on real-world studies.
“Patient-reported outcomes (PROs) have been discussed as an important additional outcome to assess treatment efficacy, especially in severely affected adult patients, in which common motor function tests are not applicable,” the researchers wrote.
In addition, while patients’ individual expectations for a specific therapy may influence treatment response (known as the placebo effect), this association has not been explored yet in SMA patients.
Now, researchers at Hannover Medical School, in Germany, set out to evaluate adult SMA patients’ expectations before and during Spinraza treatment, and the therapy’s benefits as assessed by patient-reported or objective measures.
The study enrolled 24 adults (15 men and nine women) with SMA either at the start of (16 patients) or during Spinraza treatment (eight patients) given at the hospital between 2017 and 2019. Participants were followed for up to 10 months.
A total of 14 adults had SMA type 3, nine had SMA type 2, and one had type 4 disease (those with SMA type 3 and 4 were evaluated together). Patients’ mean age was 38.9 (age range 19.8–65.4 years) and they had lived with the disease for a mean of 31.1 years.
Ten adults were able to walk, 10 others had scoliosis, six needed temporary non-invasive ventilation, and two required a feeding tube.
Participants were asked to report their individual treatment expectations and to complete the Stanford Expectations of Treatment Scale (SETS), a validated questionnaire to assess patients’ expectations toward a new therapy, before (14 patients) and during Spinraza treatment.
Patient-reported outcomes were evaluated through a questionnaire (developed based on their individual expectations) in which participants had to indicate improvement or worsening in 18 conditions during Spinraza treatment.
Results showed that most participants reported high effectiveness expectations (83%) and complete confidence in Spinraza (83%), but no expectations that the therapy would cure their condition (91%). Negative expectations — worries, fears, and nervousness about negative effects — were reported less frequently (22%–30%).
Adults with milder disease reported greater expectations that Spinraza would cure their disease, and those with longer disease duration indicated more negative expectations before treatment.
Pre-treatment effectiveness expectations remained stable over 10 months of treatment, while negative expectations, such as nervousness about Spinraza’s negative effects, were reduced considerably over time.
The most frequently reported expectations were an increase in muscle strength (79%) and disease stabilization (54%). A total of 18 adults (75%) reported clinical improvements, with increases in muscle strength (67%), endurance (63%), and independence (42%) as the most common.
Three patients (13%) indicated disease stabilization (no improvement or worsening), while three others (13%) reported only symptom worsening, with two of them discontinuing treatment.
These findings highlighted “that positive expectations were met in the vast majority of [adult SMA patients],” the researchers wrote.
Patients’ mean scores for HFMSE and RULM showed a tendency to increase during treatment (indicative of improved motor function), particularly in patients reporting improvements. The team noted, however, that the degree of these increases typically would be considered non-clinically meaningful.
“Minor improvements, such as an increase in thumb movement, which may have a meaningful impact on a patient’s independence and communication/ability to work, are … not captured by the HFMSE and also would be missed by the RULM score,” the researchers wrote.
Therefore, patient-reported outcomes may be more sensitive measures to assess treatment effectiveness in adult SMA patients and those with more advanced disease, the team noted.
In addition, there was no significant association between pre-treatment expectations for Spinraza and patient-reported or objective motor function outcomes, suggesting that treatment expectations did not influence treatment response.
Notably, a higher body mass index (a measure of body fat) was significantly associated with more frequently reported clinical worsening during Spinraza treatment. “Further studies addressing potential weight-dependent treatment response need to be performed,” the researchers wrote.
The team emphasized that standardized patient-reported outcome measures for adult SMA patients are urgently needed, as well as future multi-center studies with longer follow-up period to confirm these findings.
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