A new comprehensive review of spinal muscular atrophy (SMA) therapies indicates that while motor function improves across the board with treatments like nusinersen (Spinraza), risdiplam (Evrysdi), and onasemnogene abeparvovec-xioi (Zolgensma), significant gaps remain in respiratory and nutritional outcomes. The analysis, encompassing 21 studies and 1,374 patients, underscores the importance of early intervention while also pointing to unmet needs in managing the disease's broader impact.
The review, published in The European Journal of Paediatric Neurology, synthesizes data from multiple studies to provide a comparative look at the long-term effects of the three approved SMA treatments. Researchers, led by Doris Giess, M.B.B.S., M.P.H., of the Austrian Institute for Health Technology, found that motor function improvements varied based on the timing of treatment initiation and the patient's baseline function, with earlier intervention consistently yielding better results.
Motor Function Improvements
All three therapies demonstrated effectiveness in enhancing motor function over a 48-month follow-up period. The consistency in motor skill enhancement across different treatments marks a significant step forward in SMA management.
Respiratory and Nutritional Challenges
Despite the motor function improvements, the review revealed no significant improvements in respiratory and nutritional outcomes. In some severe SMA cases, the need for respiratory and nutritional support even increased over time. "Given that respiratory issues are the primary non-neurological complication and leading mortality cause in SMA, this finding is critical," Giess and her colleagues wrote, highlighting a crucial area of unmet need.
Quality of Life Considerations
Another key finding was the scarcity of studies incorporating quality of life endpoints. This lack of data makes it difficult to fully understand how these therapies impact patients beyond efficacy and safety measures. The authors emphasized the necessity for future research to include comprehensive quality of life assessments.
Cost and Ethical Implications
The high cost of SMA therapies, combined with uncertainty about the duration of motor improvements, presents ongoing challenges for patients, physicians, and payers. The study authors noted the ethical complexities, stating, "The fact that currently the treatments appear at most to change the disease trajectory (particularly in SMA 1) from certain death to severe chronic illness with unknown long–term prognosis, initiates a difficult ethical discussion."
