Switching SMA treatments in UK based on practical needs: Study
No unexpected disease progression observed before patients made switch
Children living with spinal muscular atrophy (SMA) in the U.K. can switch treatments based on practical needs and preferences without experiencing unexpected disease progression, according to a study that drew on data from the SMA REACH UK database.
“The availability of treatments in the United Kingdom has fundamentally influenced treatment choices, but deterioration in a treatment was not identified as a factor in switching treatments,” researchers wrote. “Further work will be needed to investigate the long-term trajectory of these patients.”
Their study, “Characteristics of Patients With Spinal Muscular Atrophy Who Have Switched Treatments: A Multi-Center Experience in the United Kingdom,” was published in Muscle & Nerve.
SMA is chiefly caused by mutations in the SMN1 gene that result in a shortage of SMN, a protein needed for the survival of motor neurons, or the nerve cells that control voluntary movements. Without SMN, motor neurons die, causing progressive muscle weakness.
Study looked at why patients switch between Spinraza, Evrysdi, Zolgensma
In the U.K., as in other countries, multiple disease-modifying treatments have become available in the past few years, allowing patients to switch treatments with health authority approval. In the study, the researchers looked at the reasons for switching between Spinraza (nusinersen), Evrysdi (risdiplam), and Zolgensma (onasemnogene abeparvovec-xioi).
The study included data from 375 children diagnosed with SMA across 19 sites. Of the 289 children who started with Spinraza, 21% switched to Evrysdi and 16% switched to Zolgensma. Of the 86 children who started with Evrysdi, a smaller percentage (5%) switched to Zolgensma.
Among those who switched from Spinraza, children switching to Evrysdi mostly had SMA type 1 and type 2, whereas those who switched to Zolgensma almost always had SMA type 1. Also, the children who switched treatments, regardless of therapy, were significantly younger at the start of the study than those who stayed on Spinraza, as were the children who switched to Zolgensma vs. Evrysdi.
Patients who switched from Spinraza had more severe SMA at the beginning of the study than children who stayed on the therapy, with a higher incidence of scoliosis (sideways curvature of the spine), nutritional support, and respiratory support.
A main reason for switching included difficulty in administering Spinraza, which requires an intrathecal injection (directly into the spinal canal) every four months after an initial loading period of four doses. Another reason was that parents preferred Zolgensma, which is administered as a one-time injection.
Treatment changes likely driven by practical considerations
None of the children or their parents requested to return to their original treatment after switching. Additionally, no unexpected disease progression was observed before switching, suggesting that treatment changes were driven by practical considerations rather than worsening symptoms.
The ability to choose between treatments may benefit children and their families, allowing them to select the most suitable option based on medical and personal factors. However, this study highlights the need for further research to understand the long-term outcomes of patients who switch treatments.
“As switching therapies is possible under current treatment guidelines, this work provides a useful first insight into this growing [group] of patients. Results may be used to contextualize future work exploring the efficacy of treatments following the switch in treatment,” the researchers wrote.
Biogen, Roche, and Novartis, which market Spinraza, Evrysdi, and Zolgensma, respectively, support the collection of data for the SMA REACH UK database at a national level.
About the Author
