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

Abstract

Background: Spinal Muscular Atrophy (SMA) is a rare disease that affects 1 in 11 000 live births. Recent developments in SMA treatments have included new disease-modifying therapies that require high quality data to inform decisions around initiation and continuation of therapy. In Canada, there are no nationally agreed upon outcome measures (OM) used in adult SMA. Standardization of OM is essential to obtain high quality data that is comparable among neuromuscular clinics. Objective: To develop a recommended toolkit and timing of OM for assessment of adults with SMA. Methods: A modified delphi method consisting of 2 virtual voting rounds followed by a virtual conference was utilized with a panel of expert clinicians treating adult SMA across Canada. Results: A consensus-derived toolkit of 8 OM was developed across three domains of function, with an additional 3 optional measures. Optimal assessment frequency is 12 months for most patients regardless of therapeutic access, while patients in their first year of receiving disease-modifying therapy should be assessed more frequently. Conclusions: The implementation of the consensus-derived OM toolkit will improve monitoring and assessment of adult SMA patients, and enrich the quality of real-world evidence. Regular updates to the toolkit must be considered as new evidence becomes available.

Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy

“…Several domains must be evaluated, considering that the treatment is effective if the improvement is demonstrated in one or more of these domains: motor function, motor milestones, respiratory function, bulbar function (speech and swallowing), and nutritional data. 126 The SMArtCARE project is a platform to collect real-life outcomes data of patients with SMA in Germany, Austria, and Switzerland. It proposes standardized instruments to be used according to age and functional motor capacity (►Table 2).…”

“…132,133 Consistent with the literature, there is poor availability of outcome measures for bulbar function. 126 Therefore, we suggest that the evaluation of therapeutic efficacy in this domain be done through the need for a nasogastric tube or gastrostomy, video fluoroscopy swallow study, or clinical assessment of the risk of aspiration. 131 Fatigue is a complex issue but a frequent complaint of SMA patients, especially in types 2 and 3.…”

“…The poor availability of outcome measures that assess important domains of quality of life, fine motor skills, and endurance (particularly in non-sitter and sitter populations) led to the routine assessment of these domains not being included in this consensus. 126,135 The patient's perception of satisfaction, response to treatment, and adverse effects are important, but there are no outcome measures for these domains. 136 The frequency with which patients should be reassessed needs to be better defined in the literature and varies greatly according to the practice of different care centers in the world.…”

“…►Chart 6 provides a summary of genetic counseling recommendations for SMA-5q. SMA-5q is an autosomal recessive disorder mostly associated with a homozygous deletion in Table 3 Global assessment of SMA-5q patients 32,126,128 A more complicated situation happens when one of the parents has two intact SMN1 genes, a condition seen in about 6% of the parents. 142 There are three possible explanations: 1) de novo deletion occurs in about 2% of the cases, most are of paternal origin, and the risk of recurrence is rare; 2) germline mosaicism is another possible explanation, but its diagnosis is complicated and 3) approximately 4-8% of the carriers have a heterozygous condition with two SMN1 genes in cis in one chromosome and a deleted SMN1 gene in the other allele.…”

Nusinersen (Spinraza)

“…The censuses were reached using 2 rounds of modified Delphi method. 61 Elsheikh et al conducted the 6MWT in 30 ambulatory adults with SMA and found that 97% of patients were able to complete the test, suggesting feasibility for assessment in the targeted population. 62 Construct validity was assessed using convergent validity in 3 studies in 65 ambulatory patients with type II and III SMA and ages ranging from 4 to 55.3 years.…”