Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence suggests that mexiletine is better than placebo at reducing the symptoms of myotonia, but there is no direct comparison with other sodium channel blockers, which raises uncertainty about its relative effectiveness. The MYOMEX trial, while indicating some efficacy, did not include active comparators, limiting the ability to claim superiority over existing treatments.
Cost effectiveness
The cost-effectiveness estimates for mexiletine compared with best supportive care fall within the range that NICE considers acceptable. The committee concluded that mexiletine is cost-effective for people with NDM, with an ICER around £19,039 per QALY gained, which is below the threshold of £20,000.
Quality of life
The evidence indicates that mexiletine improves quality of life as measured by the Individualised Neuromuscular Quality of Life (INQoL) questionnaire. Although the trial primarily used a condition-specific measure, the committee acknowledged that generic quality-of-life instruments can capture broader health impacts, suggesting a moderate but positive effect on HRQoL.
Supporting Domains
Safety and Adverse Effects
Mexiletine has an acceptable safety profile, with manageable side effects reported in clinical trials. The committee noted that while there are concerns about potential adverse effects, these are generally mild to moderate and do not significantly undermine the treatment’s overall value.
Comparator Selection
The committee noted that the company compared mexiletine with placebo rather than other sodium channel blockers, which are used in clinical practice. This raises concerns about the appropriateness of the comparator, as it does not reflect the current treatment landscape for NDM.
Patient Population and Subgroups
The MYOMEX trial included a representative sample of patients aged 18 to 65 with genetically confirmed NDM, which is broadly generalizable to the Healthcare population. However, there were some limitations in subgroup analyses, particularly regarding older patients.
Care Pathway Integration
Mexiletine can be integrated into existing care pathways with minor adjustments, as it is already established in clinical practice for treating NDM. The committee noted that no significant new infrastructure or training is required for its implementation.
Resource Use and Cost Implications
While the economic model suggests that mexiletine is cost-effective, there are concerns about the assumptions made regarding resource use and the potential overestimation of costs for patients not receiving treatment. This uncertainty may impact the overall budget impact.
Evidence Quality and Robustness
The evidence base is primarily derived from the MYOMEX trial, which has limitations such as small sample size and potential biases due to unblinding. While there is supporting evidence from other studies, the overall robustness of the evidence is moderate.
Uncertainty, Sensitivity, and Broader Impacts
There is significant uncertainty surrounding the clinical effectiveness and cost-effectiveness of mexiletine, particularly due to the lack of direct comparisons with other sodium channel blockers. This uncertainty could affect its broader acceptance and use in clinical practice.
