Poor Spinraza Adherence Leads to More Illness, Healthcare Costs
Not having Spinraza (nusinersen) therapy as prescribed — called treatment non-adherence by clinicians — increased the frequency of co-existing diseases, required greater use of healthcare resources, and raised overall costs for patients with spinal muscular atrophy (SMA) in the U.S. and their families, retrospective research into claims data for the medication showed.
“Adherence is integral to treatment success,” the researchers noted in reporting their findings of poor consistency of Spinraza therapy among people with all SMA types studied.
“In our study of claims data in the United States, we found frequent deviations from the recommended [Spinraza] dosing schedule across SMA types 1, 2, and 3,” the team wrote, while acknowledging the large logistical challenges faced by patients and caregivers — particularly parents of young children with SMA — in ensuring longterm treatment.
“These barriers, while understandable, often result in treatment delays that, in this patient population, may result in loss of motor neuron function and disease progression. In addition, non-adherence to treatment may increase health care costs … [and] leads to poorer outcomes (e.g., respiratory illness requiring hospitalization),” they wrote.
Spinraza is a disease-modifying treatment by Biogen for all types of SMA. It is approved in the U.S. and Europe, and in more than 50 countries worldwide, including Canada, China, and Japan.
It increases the ability of cells to produce a functional SMN protein — the protein is missing in people with SMA — and is delivered intrathecally, or via the spinal canal. Patients receive an initial loading period of four doses (the first three every 14 days, and the fourth 30 days later), and then move to maintenance treatment. From there, they receive the therapy once every four months, or three times each year.
The researchers noted that Spinraza adherence requires lifelong injections into the spinal canal, which logistically presents many challenges for patients and caregivers, among them, for example, “traveling to sites for treatment, scheduling time off of work, or finding child care for unaffected siblings.” Additional concerns are the risks related to anesthesia for the medication’s administration and the potential costs to patients and their families for this surgical procedure.
Keeping up with treatments and not stopping altogether are problems for any patients needing long-term treatment, the investigators noted.
“Adherence to [Spinraza] may pose particular challenges as most patients with SMA are young children who require complex multidisciplinary care (including ongoing intrathecal treatment administration and potential specialized anesthetic and surgical procedures) at specialized centers,” they wrote.
To get real-world data on such adherence, researchers now analyzed records from Symphony Health’s Integrated Dataverse, a longitudinal patient data source that has prescription claims and medical resource use and costs from across the U.S. The data reviewed covered all payment types, from Dec. 23, 2016, to Nov. 20, 2019.
A total of 62 patients with SMA type 1, 94 patients with SMA type 2, and 462 patients with SMA type 3 were included in the analysis. The patients’ mean ages ranged from 0.67, or younger than 1 year, for some type 1 patients, to 17.53 years, for certain type 3 patients.
During the nearly three-year time span of the records, 37.1% of patients with SMA type 1 completed all four loading doses of Spinraza. A total of 43.6% of individuals with SMA type 2, and 56.3% of those with SMA type 3 also finished the four-dose loading phase.
The mean adherence rates were similar across SMA types: 71.8% for type 1, 74.4% for type 2, and 75.6% for type 3.
Looking at off-schedule doses — and allowing for a grace period of approximately seven days for the loading phase and 14 days for maintenance doses — at least one dose was received off-schedule by 56.5% of patients with SMA type 1, 73.2% of patients with SMA type 2, and 60.8% of patients with SMA type 3.
The researchers also looked at Spinraza discontinuation, which they defined as two or more consecutive missed doses based on the expected dosing schedule.
The median time for discontinuation was 18.5 months for patients with SMA type 1, with 55.2% still continuing the treatment as prescribed one year after they started.
For types 2 and 3, the median time to discontinuation was 6.2 and 14.4 months, respectively. The analysis showed that 42.4% of type 2 and 54.6% of type 3 patients were still continuing the treatment as prescribed one year after starting it.
Regardless of SMA type, less than 50% remained on treatment at the 24-month mark, or two years after starting Spinraza.
Not adhering to the treatment resulted in greater SMA-related problems, or comorbidities, across all SMA types, the researchers reported. Such additional co-existing conditions included feeding difficulties, trouble breathing, failure to thrive, and muscle weakness.
Additionally, patients who stopped treatment showed more neurodevelopmental disorders, sleeping disorders, and chronic pulmonary disease than those who stuck with the regular Spinraza doses.
The most common co-existing conditions varied according to SMA type, with feeding difficulties prevalent among those with SMA type 1, and generalized muscle weakness most common for SMA type 2 patients. For those with type 3, scoliosis was most common.
Across all SMA types, patients who were missed or discontinued treatment required much greater use of health care resources — measured in days per patient per year, or PPPY — than those who were adherent to their dosing schedules.
Discontinuation also was associated with greater health care costs, especially for type 2 and 3 patients
Non-adherent patients with SMA type 2 had a mean cost of $146,830 PPPY, compared with $51,937 for those who adhered to therapy. For patients with SMA type 3, these costs were $105,657 PPPY for the non-adherent group and $74,647 PPPY for the adherent group.
Over the analysis period, patients with all types of SMA who discontinued Spinraza had on average greater total health care costs (excluding Spinraza costs) than those who stayed on the treatment.
These results highlight the need for better treatment adherence for SMA patients, the researchers said.
While noting the many barriers that can affect adherence, the investigators said that identifying these challenges and educating patients and caregivers as to the importance of closely following medication protocols is critical to limiting comorbidities and preventing additional costs to patients and their families.
“Treatment delays for patients with SMA may result in loss of motor neuron function, disease progression, and increased HCRU [healthcare resource utilization] and costs,” the researchers concluded.