Adult SMA Patients Benefit from Spinraza Treatment, Small Study Suggests
Treatment of adult spinal muscular atrophy (SMA) patients with Spinraza (nusinersen, by Biogen) seems to be beneficial, despite the challenges associated with its administration, a small study suggests.
Patients reported either stabilization of motor function or reduction in the severity of their symptoms. However, longer observational studies are needed to establish evidence-based conclusions for this patient population, the researchers noted.
The study, “Experiences from treating seven adult 5q spinal muscular atrophy patients with Nusinersen,” was published in Therapeutic Advances in Neurological Disorders.
While Spinraza is approved to treat both infants and adults, many of its pivotal clinical studies were conducted only with children. As such, data about  adults being treated with Spinraza is scarce.
Some studies have reported that intrathecal administration (given directly into the spinal canal) of Spinraza is safe and feasible in adults and adolescents with SMA, although challenging for those with SMA type 2 who have had spinal fusion surgery.
A German study also reported that Spinraza stabilized or improved motor and lung function of a group of patients with SMA type 3.
However, “no follow-up data describing the clinical course of adult patients receiving treatment with [Spinraza] has been published to date, and no reports on adult SMA type II patients exist so far,” the researchers wrote.
Now, researchers at Jena University Hospital, in Germany, report on the first 10 months of Spinraza treatment of seven adults with SMA types 2 or 3, who were treated at the hospital from August 2017 to May 2019.
Patients’ median age was 42, four had SMA type 2 and three had SMA type 3. Researchers evaluated all patients before treatment, and then at two, six, and 10 months after treatment.
Motor function was assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE), the Revised Upper Limb Module (RULM), and the 6-Minute Walk Test (6MWT).
Physical functioning in activities of daily living was evaluated using the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and quality of life was assessed using the EUROQoL EQ-5D. Patient-reported outcomes were scored using the Measure Yourself Medical Outcome Profile 2 (MYMOP-D, German translation of MYMOP2).
Regarding therapy delivery, researchers reported that, overall, intrathecal administration was feasible. The conventional lumbar punctures performed in three patients with SMA type 3, who were able to sit unassisted or with assistance of just one person, did not require more attempts than those performed on healthy individuals.
In the remaining four patients, clinicians performed CT-guided lumbar punctures, of which three required fluoroscopic guidance. Â However, “[f]luoroscopic guidance was arduous in presence of severe spinal deformities, postoperative alterations, and demineralization [loss of bone minerals],” the researchers wrote.
In the total treatment period of 10 months, six of the seven patients received all six doses of Spinraza. These patients reported subjective improvements in motor function, which positively affected their daily lives.
One patient was not able to receive the fifth and sixth doses due to the development of an ulcer in his lower back near the injection site. At six months of follow-up, this patient reported decreasing strength, but less difficulty swallowing (dysphagia), and decided to discontinue treatment.
In the total 40 applications of Spinraza, no severe adverse events (side effects) were reported. The ones noted — headache following lumbar puncture in two patients and excessive protein in urine (proteinuria) in one patient — were consistent with those reported in the literature.
No clinically meaningful changes were observed for any of the seven patients in regards to the ALSFRS-R, pulmonary assessments, EQ-5D index, and laboratory (blood and urine work-up) assessments.
However, clinically meaningful improvements in RULM, which assesses upper limb motor function, were observed in three patients (both had SMA type 3) as soon as two months after starting Spinraza, with their scores improving by an average of 15.7 points after 10 months of treatment. The average change for all six patients who received six doses of Spinraza was an increase of 7.7 points after 10 months of treatment.
The same three patients who demonstrated greater improvements in RULM, had an increase in HFMSE scores of 9.3 points after 10 months of treatment, reflecting improvement in overall physical ability. The mean change for all six patients was an increase of five points.
The researchers offered several explanations for the earlier results in RULM scores, namely its possibly more sensitive nature to subtle motor changes, when compared to HFMSE, or a possible earlier effect in motor neurons of the upper limbs.
Only one patient was able to perform the 6MWT, walking 275 meters (300 yards) at baseline, 327 meters (357 yards) at six months, and 343 meters (375 yards) at 14 months (an improvement of 25% from the beginning of the study). Three patients performed the MYMOP-D weekly during 10 months, one of whom had increasing scores by more than one point that indicated improvement in handwriting and general well-being after six months of treatment.
All four patients with SMA type 2, but none with type 3, had elbow contractures. Moreover, three of four patients with SMA type 2 who reported swallowing difficulties at baseline said they experienced a decrease in this symptom within the first 10 months of Spinraza administration.
“A decrease or stability in dysphagia and thereby a decrease or stability in the risk for aspirational pneumonias and the need for nutritional support (percutaneous endoscopic gastrostomy) is a major therapeutic aim for most of the weaker SMA type II patients,” the researchers wrote.
One of the patients with SMA type 3 who showed stable results in the assessments during the first 10 months of treatment went on to receive Spinraza for a total of 22 months (nine doses). At his 14 month-assessment, the RULM score increased by 11 points and stayed at this level until the date the study was published. In his 22-month assessment, the HFMSE score increased by nine points.
Researchers noted that due to the small and varied group of patients and the short study period, no definite conclusions can be drawn about the clinical benefits of Spinraza in this patient population.
However, it is important to note that the patients had an average progression of disease of 36 years since the onset of symptoms, and that in the three years before Spinraza their symptoms and condition had worsened.
“Time, and increasing numbers of treated adults after the, only recent, approval of this treatment, will show whether the currently established motor assessments are able to sufficiently depict clinical status in this group of patients, and if Nusinersen can stabilize, or even improve, the situation for adult patients to a similar degree as is the case for children,” the researchers concluded.
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