Treatment of spinal muscular atrophy (SMA) with Spinraza (nusinersen) through the spinal canal is feasible and leads to high patient compliance as long as it’s done under the supervision of an experienced multidisciplinary team, according to a single-center study in Italy.
The study, “Intrathecal nusinersen treatment for SMA in a dedicated neuromuscular clinic: an example of multidisciplinary and integrated care,” appeared in the journal Neurological Sciences.
Available evidence has shown that treatment with Biogen’s Spinraza via the spinal canal — intrathecal (IT) delivery — is relatively safe and well-tolerated, despite some initial concerns over repeated injections. A single-center study from Germany reported the benefits of a structured protocol in administering the treatment.
In this study, Italian researchers also emphasize the importance of an adequately experienced team for the success of Spinraza programs across different centers. They described their experience using Spinraza as a treatment for 50 patients with SMA types 1-3 at the NEuroMuscular Omniservice (NEMO) Clinical Center, a neuromuscular patient-centered clinic in Milan.
All patients received four IT Spinraza injections within two months (loading phase), followed by injections every four months in the maintenance phase. Routine laboratory tests, including blood clotting screening, were conducted prior to treatment.
The multidisciplinary team at NEMO includes neurologists, pulmonologists, a physiatrist, therapists, a nutritionist, nurses, and clinical psychologists. An anesthetist and a pediatrician were included during IT infusions in infants and older children.
The Italian SMA Family Associations took care of transportation and lodging, and provided consistent feedback on patients waiting for treatment who were on a priority list according to age and disease severity. Since Spinraza’s approval, the organization has supported physicians and families to promote access at local sites.
Of the 50 patients enrolled, 29 had SMA type 1 (mean age of 5 years, ranging from 3 months-15 years) and received treatment within six months after Spinraza’s approval. Six of these SMA type 1 patients were newly diagnosed. The remaining 21 patients included 11 with SMA type 2 (mean age of 5.9 years, ranging from 1-17 years) and 10 with SMA type 3 (mean age of 22.5 years, ranging from 4.3-58 years).
Starting in November 2017, national health regulatory authorities in Italy recommended that Spinraza be administered locally at certified sites to favor accessibility and reduce waiting lists. As a result, 12 of the patients with SMA type 1 were redirected to their regional sites.
Prior to the first injection, a team consisting of a neurologist, a child neurologist, a psychologist, and a child therapist met with the families and discussed the program as well as preliminary results from previous trials including the risk-benefit ratio of multiple IT injections. Spinraza’s safety profile and possible adverse effects from the spinal tap were also addressed. Additional meetings were planned as needed. A dedicated psychologist was also available throughout the course of treatment.
The team and the families also discussed the need to maintain mandatory visits to assess motor, respiratory, and nutritional function, as well as monitoring for scoliosis — curvature of the spine — and growth parameters.
“It was important for the team that the concept of cure was conceived by the families and the patients beyond the pharmacological treatment and that patients understood how important it is to comply to the assessments and treatments,” the researchers wrote.
Patients with SMA type 1 warranting ventilator-assisted breathing but whose parents refused this approach were only included in the program if the parents allowed noninvasive ventilation during the procedure.
Patients’ motor function — via the CHOP-INTEND and the Hammersmith Infant Neurological Examination scales — as well as specific body measures — ulnar (in the forearm) length, weight, cranial, and thoracic circumferences — were assessed at the start of treatment and at 15, 30 and 60 days and then every four months during treatment.
Patients were also video-recorded and all underwent a spinal X-ray. Additionally, their nocturnal oximetry — to measure oxygen saturation in the blood — and transcutaneous (across the skin) CO2 were determined at the study’s start and after six months of treatment.
In children, the first injection was performed in a surgical setting by a pediatrician or a child neurologist in the presence of an anesthetician, if needed. A respiratory physiotherapist, as well as the child neurologist and/or neurologists, helped with ventilation. Injections in adults were performed by a neurologist in an outpatient setting in the presence of an anesthetician if sedation was needed.
Patients were then monitored by a child neurologist, neurologists, therapists, and nurses. Patients, parents, and caregivers were instructed to take note and inform the referral center of any clinical event occurring between injections. Adherence to recommendations was confirmed by regular phone interviews. Subsequent injections were usually confirmed one week prior to admission.
Although three patients dropped out due to technical difficulties with the procedure, adherence and compliance to the treatment were high. No patients missed their scheduled injections.
No patients showed severe adverse events considered related to Spinraza. Only three experienced temporary elevations in body temperature, headache, and nausea. Two had slight postural reddening and skin edema, or swelling. Four patients experienced clinically nonsignificant changes in heart rhythm after the loading phase. In addition, three adults experienced headache, nausea, and vomiting for 48 hours after the first injection, which responded to paracetamol.
Ten patients had mild, four moderate, and six severe scoliosis. The injections were considered too burdensome in only three of these patients.
“The experience with nusinersen at the NEMO Center [irrespective of age and severity] is that the treatment is feasible, accessible, and replicable provided that there is a multidisciplinary team having experience and training in SMA,” the scientists concluded.