Spinraza Eases Fatigue in Adults With SMA But Benefit Wanes, Study Finds

Spinraza significantly eased fatigue in adults with spinal muscular atrophy (SMA) after six months of treatment, as measured by the patient-reported Fatigue Severity Scale (FSS), a small study found. 

But this relief was no longer statistically significant after 10 months, its researchers wrote, possibly due to the waning effect of therapy that adults report feeling in the month prior to a next dose.

The study, “Fatigue in adults with spinal muscular atrophy under treatment with nusinersen,” was published in the journal Nature Scientific Reports. 

Fatigue is a natural response to stress or physical exertion regardless of health. But in people with SMA — marked by muscle atrophy due to the progressive loss of motor neurons — fatigue has been described as an overwhelming feeling of exhaustion after physical activity. 

This disease is caused by mutations in the SMN1 gene that carries the instructions for making the SMN protein, which is essential for motor neurons survival and muscle health, and is deficient in SMA patients. 

Spinraza (nusinersen), a disease-modifying therapy developed by Biogen, works to improve motor function by enhancing SMN production in a backup gene, called SMN2, leading to higher levels of this key protein. It is given to all patients as a 12 mg intrathecal (spinal canal) injection once every four months, after an initial loading dose.

While Spinraza has been found to ease motor function-related fatigue in children with SMA, its effects on fatigue in adult patients has not been fully investigated. 

“Fatigability in patients with [SMA] is an often overlooked symptom in addition to muscle weakness,” the researchers wrote. 

Scientists at the University Hospital Essen in Germany recruited 28 SMA patients, ages 19 to 61. Ten were classified as type 2, and 18 as type 3.

Ten patients were able to walk, and 18 were non-ambulatory. Seven had a history of spinal fusion surgery to relieve the pain caused by unstable vertebrae (spondylodesis). 

Fatigue was assessed using the Fatigue Severity Scale (FSS), a patient-reported questionnaire that measures the degree of subjective fatigue. FSS consists of nine items, in which higher scores indicated more severe fatigue. Scores were obtained before treatment (at baseline), then after six and 10 months of treatment. 

Motor function scores were determined using the 6-minute walk test (6MWT) and the Hammersmith Functional Motor Scale Expanded (HFMSE). The 6MWT measured the distance a patient walks within six minutes, and HFMSE assesses activities of daily living. 

At baseline, the average FSS score for all patients was 4.61, ranging from a minimum of 2 and a maximum of 7 (abnormal fatigue is considered a score of 4 or more; severe fatigue a score of 5 or more). After six months of treatment, the average FSS score fell to 3.92, representing a statistically significant reduction. 

After 10 months of treatment, the average FSS score was found to be 3.84. While lower, the difference was not statistically significant compared to baseline FSS. 

In ambulatory patients, which were those with SMA type 3, six months of Spinraza use significantly reduced — from 4.66 to 3.74 — the average baseline FSS score. Again, however, the reduction in FSS was not significant after 10 months of treatment.

In the 18 patients who could not walk, nine with type 2 and nine with type 3, a significant reduction in FSS — from 4.58 to 4.02 — was also seen after six months of Spinraza therapy, but not after 10 months. 

In this study, FSS was calculated before the next scheduled dosing. As such, “adult patients … frequently report a subjective loss of efficacy during the final four weeks before the next administration of nusinersen (personal communication), which may interfere with the FSS assessment,” the researchers wrote. 

As this study had no control group, “placebo effects cannot be ruled out in explaining the transient reduction in the FSS after 10 months of treatment in comparison to baseline conditions,” they added. 

Scores in the 6MWT rose after six and 10 months of treatment in ambulatory patients, and there was a moderate correlation between lower FSS scores and longer distances walked in the 6MWT. Higher HFMSE scores at six and 10 months weakly correlated with the lower FSS scores. 

“Our data demonstrates clinically meaningful fatigue in patients with adult [SMA] types 2 and 3, which is reduced transiently under treatment with [Spinraza],” the researchers concluded.