The authors emphasize the value of subgroup analyses for tracking patterns in spinal muscular atrophy (SMA), as opposed to drawing mean conclusions across entire cohorts.
Real-word and subgroup analyses in spinal muscular atrophy (SMA) provide great reference data for long-term comparison. This approach can lead to valuable findings that better assess patterns throughout the various SMA types, rather than tracking average changes throughout entire cohorts.
A recent analysis published in European Journal of Neurology took a closer look at 4-year outcomes in patients with SMA type 2 (SMA2) and type 3 (SMA3); however, rather than adding to the body of literature that reports on disease-modifying treatments, the researchers sought to study changes in patients’ Hammersmith Functional Motor Scale Expanded (HFMSE) and with additional factors in mind such as functional status, age, and number of spinal motor neuron 2 (SMN2) copies.1
Pediatric SMA professionals designed the HFMSE in 2003, primarily to evaluate the motor abilities and disease progression of children with SMA2 and SMA3. The scale is a viable measure for both children and adults. A composite score, accounting for 20 physical activities, helps clinicians and health care providers create a personal history for patients’ physical abilities. Over time, changes in patients’ ability to stand, crawl, roll, sit, and more allow them to reliably interpret improvements and decline in motor functioning. These records are invaluable for informing treatment approaches, confirming the efficacy of current therapeutics, and the makeup of the HFMSE ensures that it is replicable, reliable, and easy to use.2
In the present study, the HFMSE evaluated 33 items with scores ranging from 0-2 (0 = unable to do a given physical activity; 1 = physical activity achievable with certain modifications; 2 = can perform activity without modification).1
Researchers utilized a combination of retrospective analysis and prospective data collection, drawing from multiple international data sets such as the Pediatric Neuromuscular Clinical Research Network for SMA in the US, Italy, and UK-SMA REACH. Additionally, data were collected from a Spain-based and Belgium-based prospective network. Overall, gathered data spanned between 2003 and 2022.
In total, 388 patients with SMA were included in the final data set (SMA2 = 226; SMA3 = 162). The authors noted that nearly 60% of individuals with SMA3 experienced clinical onset before the age of 3 (SMA3a) and just under 25% experienced clinical onset after 3 years of age (SMA3b).
Four years following their first clinical visit, patients with SMA2 exhibited a –2.2 change in HFMSE, with approximately a –0.58 change occurring each year. A sensitivity analysis for the SMA2 cohort revealed a 4-year change of –3.94 (95% CI, –4.29 to –2.39), estimating a –0.69 change annually (95% CI, –0.87 to –0.50). The researchers witnessed the largest average change for sitters between the ages of 5 and 14 years, and the most minimal change in individuals who lost the ability to sit without support.
The SMA3 cohort experienced a 4-year change of –2.75, or, after the sensitivity analysis, –2.82 (95% CI, –4.29 to –1.34). Annual changes were approximately –0.82, or –0.81 (95% CI, –1.11 to –0.52) after the sensitivity analysis. In this group, the biggest mean motor changes occurred for individuals aged 7 to 15 years—and in those over 15 years in the SMA3a subgroup.
Notably, baseline scores and patient age were the most predictive of change over the 4-year period.
“Whilst this information helps understand when deterioration is perceived as clinically meaningful by individuals or caregivers, the observed variability also reinforces the idea that mean changes across different SMA cohorts are not reliable bench-marks, as they encompass a wide spectrum of individual variations in disease progression and treatment response,” the authors concluded.
References
1. Coratti G, Bovis F, Pera MC, et al. Long-term natural history in type II and III spinal muscular atrophy: a 4-year international study on the Hammersmith Functional Motor Scale Expanded. Eur J Neurol. 2024;31(12):e16517. doi:10.1111/ene.16517
2. McKibben JC. What Is the Hammersmith Functional Motor Scale for SMA? mySMAteam. October 25, 2021. Accessed November 27, 2024. https://www.mysmateam.com/resources/what-is-the-hammersmith-functional-motor-scale
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