Long‐Term Effects of Nusinersen Dosing Frequency on Adult Patients With Spinal Muscular Atrophy: Efficacy of a 6‐Month Dosing Interval

TL;DR

This study shows that a 6-month dosing interval of nusinersen works well for ambulatory adult SMA patients but is less effective for nonambulatory patients compared to a 4-month interval.

Contribution

The study evaluates the long-term efficacy of a 6-month nusinersen dosing protocol in adult SMA patients, comparing it to a 4-month protocol.

Findings

Ambulatory patients showed sustained improvements in HFMSE scores over 39 months with a 6-month dosing interval.

Nonambulatory patients had less favorable outcomes compared to the European cohort using a 4-month interval.

The 6-month protocol did not lead to clinically meaningful deterioration in nonambulatory patients.

Abstract

Spinal muscular atrophy (SMA) is a genetic disease caused by the degeneration of spinal motor neurons due to a deficiency in survival motor neuron protein (SMN) protein, leading to progressive muscle atrophy and weakness. nusinersen, an antisense oligonucleotide that increases SMN protein expression, has shown effectiveness in both pediatric and adult patients with SMA. While it is administrated every 4 months during the maintenance period in most countries, the dosing interval is 6 months in Japan. The impact of this dosing difference on long‐term outcomes is not fully understood. This study evaluates the long‐term efficacy of the 6‐month dosing protocol of nusinersen in adult SMA patients.

We assessed 14 adult patients treated with nusinersen every 6 months over a period of up to 39 months using the Hammersmith Function Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM). The results were compared with those from a recent cohort study of adult SMA patients in Europe.

For ambulatory patients, the mean changes in HFMSE scores at 15, 27, and 39 months were 6.7, 8.3, and 8.0 points, respectively. These results were similar to those observed in the European cohort. In contrast, for nonambulatory patients, the mean changes in HFSME scores were –0.3, –1.4, and –1.3 points, and the mean changes in RULM scores were 2.0, 0.5, and 1.0 points at the same time points. These results were generally less favorable compared to the European cohort but did not reach clinically meaningful deterioration.

The findings of this study suggest that the 6‐month nusinersen dosing protocol provides sustained long‐term benefits for ambulatory adult SMA patients. For nonambulatory patients, the 6‐month protocol appears less effective than the 4‐month protocol. We believe that future nusinersen treatment strategies for adult SMA patients should be flexible, with adjustments based on disease severity. In particular, increasing the dosing frequency and/or dosage in nonambulatory patients may lead to greater improvements.

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