An observational cohort study on impact, dimensions and outcome of perceived fatigue in adult 5q-spinal muscular atrophy patients receiving nusinersen treatment

Abstract

Background Efficacy of nusinersen in adult 5q-spinal muscular atrophy (SMA) patients regarding motor function has recently been demonstrated. However, additional outcome measures are needed to capture non-motor improvements. Fatigue is a common and disabling symptom in neurologic diseases, but little is known about its frequency, characteristics and associated factors in SMA. Objective To characterize fatigue in SMA patients receiving nusinersen, identify associated factors and evaluate fatigue as potential patient-reported outcome measure (PRO). Methods We assessed fatigue in adults with genetically confirmed 5q-SMA in a prospective longitudinal monocentric study using the Fatigue Severity Scale (FSS) and the Multidimensional Fatigue Inventory (MFI). Factors associated with fatigue including health-related quality of life (HRQOL) were evaluated. Results 75% of participants were abnormally fatigued with highest scores in the dimensions physical, followed by general fatigue and reduced activity. 53% agreed that fatigue was among their three most disabling symptoms. Reduced activity was reported more extensively by participants with ≥ 4 copies of the survival of motor neuron 2 gene and better motor function. General and mental fatigue correlated positively with age and disease duration. HRQOL was inversely correlated with physical fatigue, which was not associated with disease or participant characteristics. During 14 months of nusinersen treatment, fatigue measures remained mostly stable with a trend towards improvement in reduced activity, general and physical fatigue. Conclusion Fatigue is a frequent and relevant complaint in adult SMA patients. Fatigue should be taken into consideration as additional outcome measure, but needs further evaluation in a larger patient cohort over a longer observation period.

Fatigue, physical activity and associated factors in 779 patients with myasthenia gravis

“…The fatigue scores in the present cohort were slightly lower than found in patients with Parkinson disease [52], chronic fatigue syndrome [53], multiple sclerosis [24] and almost similar to fatigue scores in post-stroke patients [20] and patients with other autoimmune diseases [54]. One previous study has published results of MFI measurements in patients with neuromuscular diseases, finding a fatigue level in adult patients with spinal muscular atrophy lower (except for physical fatigue) than found in patients with MG [25]. Due to a large variation in measurement tools of fatigue across studies, comparison of results in previous MG studies are difficult.…”

“…The MFI-20 has been validated and/or used in several clinical and healthy populations since 1995, including patients with neurological diseases, e.g. multiple sclerosis, stroke, polio and spinal muscular atrophy [19][20][21][22][23][24][25]. The MFI-20 was in 2000, in a study of fatigue in the Danish background population, validated and translated into Danish [26,27].…”

Nusinersen Wearing-Off in Adult 5q-Spinal Muscular Atrophy Patients

“…They are assumed to benefit from nusinersen treatment; however, treatment effects are not sufficiently pictured by commonly used motor function outcome measures due to known floor effects and the lack of specific assessments addressing the needs of this patient group [ 8 ]. Therefore, patient-reported outcomes have been widely discussed to close this gap, and recent results confirm patients’ perceived efficacy even if non-ambulatory and severely affected [ 12 , 13 , 14 ]. Only recently, a study by Yeo CJJ et al described two patients under regular nusinersen dosing reporting wearing-off phenomena.…”

A Canadian Adult Spinal Muscular Atrophy Outcome Measures Toolkit: Results of a National Consensus using a Modified Delphi Method

“…Capturing additional domains is important to further increase sensitivity to detect changes and to better assess other aspects of life [12]. For example, Sansone et al described the importance of finger and hand strength, while Kizina et al and Binz et al examined the presence of fatigue [13,31,32]. Bulbar function was previously identified by Rouault et al as a priority for stabiliza-…”