Improving Care and Empowering Adults Living with SMA: A Call to Action in the New Treatment Era

Walter, Maggie C.; Chiriboga, Claudia A.; Duong, Tina; Goemans, Nathalie; Ouillade, Laëtitia; Oskoui, Maryam; Quinlivan, Ros; Vázquez-Costa, Juan Francisco; Vissing, John; Servais, Laurent

doi:10.3233/jnd-200611

Cited by 11 publications

(10 citation statements)

References 35 publications

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“…5,6,10,26 Until recently, adult SMA patients had been frequently disengaged and neglected from both health services and research studies. [27][28][29] The approval of disease-modifying treatments has resulted in a substantial rise of referrals, and an increasing interest of research in adult SMA patients. 29,30 At present, motor function scales most frequently used in adult SMA patients have been designed and validated in children.…”

Section: Discussionmentioning

confidence: 99%

“…[27][28][29] The approval of disease-modifying treatments has resulted in a substantial rise of referrals, and an increasing interest of research in adult SMA patients. 29,30 At present, motor function scales most frequently used in adult SMA patients have been designed and validated in children. However, both populations present considerable differences (e.g., in disease progression rate, contractures and scoliosis, comorbidities, etc.…) that could diversely affect the performance of motor scales.…”

Section: Discussionmentioning

confidence: 99%

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Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy

Vázquez-Costa

Povedano

et al. 2021

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Objective To assess in adult spinal muscular atrophy (SMA) patients the construct validity and responsiveness of several outcome measures. Methods Patients older than 15 years and followed-up at least for 6 months, between October 2015 and August 2020, with one motor function scale (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb module, RULM) in five referral centers were included. Bedside functional scales (Egen Klassification, EK2; Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS-R) were also collected when available. Correlations and regression models were performed to evaluate the construct validity. The monthly slopes of change were used to calculate their responsiveness. Results The study included 79 SMA patients, followed up for a mean of 16 months. All scales showed strong or very strong correlations with each other. A floor effect in motor function scales was found in weakest patients (HFMSE < 5 and RULM<10), and a ceiling effect in stronger patients (with HFMSE >55 and RULM > 35), when compared with other scales. ALSFRS-R (B=0.72) showed a strong discriminating ability between walkers, sitters, and non-sitters, and HFMSE (B=0.86) between walkers and sitters. The responsiveness was overall low, although in treated patients a moderate responsiveness was found for ALSFRS-R and HFMSE in walkers (0.69 and 0.61 respectively), and for EK2 in sitters (0.65) and non-sitters (0.60). Conclusions This study shows the validity in SMA adult patients of commonly used scales. Overall, bedside functional scales showed some advantages over motor function scales, although all scales showed low responsiveness in untreated patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy

Vázquez-Costa

Povedano

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Thus, whenever possible, functional stratification should be considered in studies addressing adult SMA patients. 25,33 Previous studies have reported a 30-60% of responders, according to the predefined MCID of motor scales. 8,11,12 However, the responder rate should also be interpreted with caution, since two important biases could lead to under-and overestimations.…”

Section: Discussionmentioning

confidence: 99%

“…overlooked the particularities of adult SMA patients, characterized by a huge clinical heterogeneity and poorly defined natural history. 25,26 Recently, the first reports of real-world evidence on the efficacy and safety of nusinersen in adult SMA patients have been published. [8][9][10][11][12][13][14] Most of them, but not all, 10 suggest nusinersen efficacy, at least in a subset of patients.…”

Section: Discussionmentioning

confidence: 99%

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Nusinersen in adult patients with 5q spinal muscular atrophy: a multicenter observational cohorts’ study

Povedano

et al. 2021

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Objective To assess safety and efficacy of nusinersen in adult 5q spinal muscular atrophy (SMA) patients. Methods Patients older than 15 years and followed at least for 6 months with one motor scale (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb module, RULM) in five referral centers were included. Clinical and patients global impression of change (CGI-C and PGI-C) were recorded in treated patients at the last visit. Functional scales (Egen Klassification, EK2; Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS-R) and the percent-predicted forced vital capacity were collected when available. Results Seventy-nine SMA patients (39 treated with nusinersen) were included. Compared with untreated patients, treated patients showed a significant improvement of 2 points (±0.46) in RULM (p<0.001) after six months. After a mean follow-up of 16 months, nusinersen treatment was associated with a significant improvement in HFMSE (OR=1.15, p=0.006), 6MWT (OR=1.07, p<0.001), and EK2 (OR=0.81, p=0.001). Compared with untreated patients, more treated patients experienced clinically meaningful improvements in all scales, but these differences were statistically significant only for RULM (p=0.033), ALSFRS-R (p=0.005), and EK2 (p<0.001). According to the CGI-C and PGI-C, 64.1% and 61.5% of treated patients improved with treatment. Being non-sitter was associated with less response to treatment, while longer time of treatment was associated with better response. Most treated patients (77%) presented at least one adverse event, mostly mild. Conclusions Nusinersen treatment associates to some improvements in adult SMA patients. Most severely affected patients with complex spines are probably those with the most unfavorable risk-benefit ratio.

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Validation of a Set of Instruments to Assess Patient- and Caregiver-Oriented Measurements in Spinal Muscular Atrophy: Results of the SMA-TOOL Study

et al. 2022

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Introduction Outcome measures traditionally used in spinal muscular atrophy (SMA) clinical trials are inadequate to assess the full range of disease severity. The aim of this study was to assess the psychometric properties of a set of existing questionnaires and new items, gathering information on the impact of SMA from the patient and caregiver perspectives. Methods This was a multicenter, prospective, noninterventional study including patients with a confirmed diagnosis of 5q-autosomal-recessive SMA aged 8 years and above, or their parents (if aged between 2 and 8 years). The set of outcome measurements included the SMA Independence Scale (SMAIS) patient and caregiver versions, the Neuro-QoL Fatigue Computer Adaptive Test (CAT), the Neuro-QoL Pain Short Form—Pediatric Pain, the PROMIS adult Pain Interference CAT, and new items developed by Fundación Atrofia Muscular España: perceived fatigability, breathing and voice, sleep and rest, and vulnerability. Reliability, construct validity, discriminant validity, and sensitivity to change (4 months from baseline) were measured. Results A total of 113 patients were included (59.3% 2–17 years old, 59.3% male, and 50.4% with SMA type II). Patients required moderate assistance [mean patient and caregiver SMAIS (SD) scores were 31.1 (12.8) and 7.6 (11.1), respectively]. Perceived fatigability was the most impacted domain, followed by vulnerability. Cronbach’s alpha coefficient for perceived fatigability, breathing and voice, and vulnerability total scores were 0.92, 0.88, and 0.85, respectively. The exploratory factor analysis identified the main factors considered in the design, except in the sleep and rest domain. All questionnaires were able to discriminate between the Clinical Global Impression—Severity scores and SMA types. Sensitivity to change was only found for the SMAIS caregiver version and vulnerability items. Conclusions This set of outcome measures showed adequate reliability, construct validity, and discriminant validity and may constitute a valuable option to measure symptom severity in patients with SMA. Supplementary Information The online version contains supplementary material available at 10.1007/s40120-022-00411-2.

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Improving Care and Empowering Adults Living with SMA: A Call to Action in the New Treatment Era

Cited by 11 publications

References 35 publications

Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy

Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy

Nusinersen in adult patients with 5q spinal muscular atrophy: a multicenter observational cohorts’ study

Validation of a Set of Instruments to Assess Patient- and Caregiver-Oriented Measurements in Spinal Muscular Atrophy: Results of the SMA-TOOL Study

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