Researchers also pointed out that objective measures of meaningful improvements in daily life activities are required to better determine treatment effectiveness in this patient population.
The study, “Nusinersen for older patients with SMA: a real‐world clinical setting experience,” was published in the journal Muscle & Nerve.
Spinraza — developed by Biogen to increase the expression of SMN, the protein lacking in SMA — became the first approved treatment indicated for SMA type 1, 2, and 3 in children and adults in the U.S. This was followed by approval in other countries, including Australia, Brazil, Japan, Switzerland, South Korea, Canada, Chile, and several other countries in Europe.
Spinraza is given intrathecally — injected directly into the spinal canal — at a recommended regimen of four doses (12 mg each) in the first two months followed by maintenance treatment every four months.
While Spinraza’s therapeutic effects have been widely demonstrated in earlier stages of the disease and in young patients up to 12 and 15 years old, data is limited about its effectiveness in older children and adults with SMA.
This data on older patients is relevant, considering that one-third of SMA patients currently receiving Spinraza are adults, according to national data from Biogen.
In the study, researchers at the University of Rochester Medical Center described the safety and effectiveness of Spinraza in 12 SMA patients (six males and six females) older than 12 years, who were followed at their clinic.
They retrospectively analyzed the patients’ electronic health data before and after treatment in terms of side effects and functional measures, including the Revised Upper Limb Module (RULM) score, time to complete a 30-foot walk, patient-reported improvements, and the 6-minute walk test (6MWT), which measures the distance a person is able to walk in six minutes.
The team noted that RULM, which assesses upper limb function through 19 tasks, was used because it was difficult for patients with severe contractures to perform or complete the Hammersmith Functional Motor Scale Expanded, which measures motor function.
Of the 12 patients, one had SMA type 1, four had type 2, and seven had type 3. Three of them were able to walk. All patients had muscle atrophy, contractures, and scoliosis (for which 10 patients underwent spinal surgery).
Patients’ mean age at treatment initiation was 22 years (age range 12 to 52), with most of them (eight patients) being 16 or older. They were followed for a mean of 17.4 months (range was four to 26 months). Ten patients had follow-up data until at least the first two Spinraza maintenance doses.
Results showed that all treatment procedures were technically successful. A total of 30 infusions were administered in the cervical (neck) region of four patients and 57 in the lumbar (lower-back) region of the spine in eight patients.
Side effects were only reported in patients receiving Spinraza in the lumbar region and included post-treatment headache in five patients and site pain in four patients. No patient had discontinued treatment at the last follow-up date.
Out of the nine patients who completed objective motor function assessments, six remained stable, and three showed motor improvements.
Patients who completed the second maintenance dose demonstrated at least a 2-point change in the RULM score, meaning that they gained the ability to perform at least one more task than before treatment.
One of the patients who was able to walk showed an improvement in 6MWT distance from 18 meters (before treatment) to 75 meters (with two standing breaks during the task), at the last follow-up (25 months).
Eight patients reported improvements in endurance and hand strength, which were critical for daily living activities, while five patients reported louder and clearer speech. Improvements were also reported in patients’ muscle strength and range of motion, ability to walk or stand, heart rate, constipation, cough strength, and reduced lung infections and subsequent hospitalizations.
These findings suggest that Spinraza administration is safe and well-tolerated, and that treatment leads to motor function stabilization or improvement in SMA patients 12 or older.
“While currently available functional outcome measures are not adequate to capture meaningful clinical changes [in daily life activities], routine administration of quality of life scales in clinical practice should be considered,” the researchers wrote.
The team noted that longer studies, as well as new objective measures, are required to determine the effectiveness of Spinraza in this patient population.