Improving the understanding of how patients with non-dystrophic myotonia are selected for myotonia treatment with mexiletine (NaMuscla): outcomes of treatment impact using a European Delphi panel

Abstract

Background: Non-dystrophic myotonias (NDMs) comprise muscle chloride and sodium channelopathies due to genetic defects of the CLCN1- and SCN4A-channels. No licensed antimyotonic treatment has been available until approval of mexiletine (NaMuscla®) for adult patients by the EMA in December 2018. This Delphi panel aimed to understand how outcomes of the pivotal phase III Mexiletine study (MYOMEX) translate to real world practice and investigate health resource use, quality of life and the natural history of NDM to support economic modelling and facilitate patient access.

Methods: Nine clinical experts in treating NDM took part in a two-round Delphi panel. Their knowledge of NDM and previous use of mexiletine as an off-label treatment prior to NaMuscla's approval ensured they could provide both qualitative context and quantitative estimates to support economic modelling comparing mexiletine (NaMuscla) to best supportive care. Consensus in four key areas was sought: healthcare resource utilization (HRU), treatment with mexiletine (NaMuscla), patient quality of life (QoL), and the natural history of disease. Concept questions were also asked, considering perceptions on the feasibility of mapping the validated Individualized Neuromuscular Quality of Life (INQoL) instrument to the generic EQ-5D™, and the potential impact on caregiver QoL.

Results: Consensus was achieved for key questions including the average long-term dosage of mexiletine (NaMuscla) in practice, the criteria for eligibility of myotonia treatment, the clinical importance of QoL outcomes in MYOMEX, the higher proportion of patients with increased QoL, and the reduction in the need for mental health resources for patients receiving mexiletine (NaMuscla). While consensus was not achieved for other questions, the results demonstrated that most experts felt mexiletine (NaMuscla) reduced the need for HRU and was expected to improve QoL. The QoL mapping exercise suggested that it is feasible to map domains of INQoL to EQ-5D. Points of interest for future research were identified, including that mexiletine (NaMuscla) may slow the annual decrease in QoL of patients over their lifetime, and a significant negative impact on QoL for some caregivers.

Conclusions: This project successfully provided data from an informed group of clinical experts, complementing the currently available clinical trial data for mexiletine (NaMuscla) to support patient access decisions.

Keywords: Delphi panel; EQ-5D; Healthcare resource utilisation; INQoL; Mexiletine (NaMuscla); Non-dystrophic myotonia; Quality of life.

Fig. 1

Criteria to select patients with NDM for mexiletine (NaMuscla) treatment. Key: EKG, electrocardiogram; EMG, electromyographic; NDM, non-dystrophic myotonia. Note: The horizontal black line indicates the 70% consensus threshold

Fig. 2

Perceived impact of INQoL domains on patient QoL. Key: INQoL, Individualized Neuromuscular Quality of Life; QoL, quality of life. Note: Higher scores indicate higher perceived impact on patient QoL. Experts were asked to rank domains of INQoL based on their perceived impact on QoL (from 1 – highest impact, to 10 – lowest impact). The overall score for each domain was derived by calculating the mean of all expert responses (assigning the most impactful domain a 10 and the least impactful domain a 1)

Fig. 3

Proportion of adult patients with NDM who experience a change in QoL over their lifetime. Key: BSC, best supportive care

Fig. 4

Perceived impact of treatment on aspects of caregiver QoL. Key: QoL, quality of life