Focused Ultrasound Thalamotomy and Other Interventions for Medication-Refractory Essential Tremor: An Indirect Comparison of Short-Term Impact on Health-Related Quality of Life

Abstract

Background: Up to 50% of essential tremor patients are refractory to medication and require alternative treatment to achieve tremor relief. This study aimed to identify and analyze evidence supporting the use of the emerging magnetic resonance-guided focused ultrasound (MRgFUS) compared to alternative stimulatory and ablative interventions for the treatment of medication-refractory essential tremor: radiofrequency thalamotomy, unilateral deep brain stimulation (DBS), and stereotactic radiosurgery. Methods: A systematic literature review was conducted to identify clinical, health-related quality of life (HRQoL), and economic evidence for each intervention. Because of the lack of comparative evidence captured, a feasibility assessment was performed to determine possible comparisons between interventions, and newly established matchingadjusted indirect comparison and simulated treatment comparison techniques were used to conduct a comparison between unilateral DBS aggregate data and MRgFUS individual patient data. Results: The systematic literature review identified 1,559 records, and screening yielded 46 relevant articles. The captured studies demonstrated that radiofrequency thalamotomy, DBS, stereotactic radiosurgery, and MRgFUS all exhibit clinical efficacy, with variation in onset and duration of tremor relief, and are each associated with a unique safety profile. The matching-adjusted indirect comparison and simulated treatment comparison results demonstrated no evidence of a difference in efficacy (measured by Clinical Rating Scale for Tremor Total) and HRQoL (measured by Clinical Rating Scale for Tremor Part C) outcomes between MRgFUS and unilateral DBS in the short term (r12 months). Conclusions: This study provides preliminary evidence that MRgFUS could elicit similar short-term tremor-and HRQoL-related benefits to DBS, the current standard of care, and allowed for the first robust statistical comparison between these interventions.

Treatment of essential tremor: current status

“…MRgFUS may provide certain advantages over other surgical interventions due to it being a non-invasive procedure 101 108 118. A recent systematic literature review concluded that the efficacy in tremor control as well as improving quality of life with unilateral MRgFUS-thalamotomy might be comparable to unilateral DBS in the short term up to 12 months after procedure 119. On the other hand, DBS is the favoured treatment in subjects with bilateral and axial tremor as well as in those with contraindications to undergo MRI before the procedure 72 73 76–78 83 101 115…”

Cost‐Effectiveness of Magnetic Resonance‐Guided Focused Ultrasound for Essential Tremor

“…On the other hand, a recently published retrospective chart review compared 59 patients who had undergone unilateral MRgFUS, DBS, or RF at a medical center in Korea and found no difference in proportions of treatment success between surgeries . In addition, a recently published systematic literature review and indirect treatment comparison study also found no difference in efficacy (measured by Clinical Rating Scale for Tremor Total) and HRQoL (measured by Clinical Rating Scale for Tremor Part C) outcomes between MRgFUS and unilateral DBS in the short‐term (≤12 months) . We assessed the cost‐effectiveness of MRgFUS compared with standard treatments in 2 distinct patient populations: those who were ineligible for invasive neurosurgery and those who were eligible.…”

“…22 In addition, a recently published systematic literature review and indirect treatment comparison study also found no difference in efficacy (measured by Clinical Rating Scale for Tremor Total) and HRQoL (measured by Clinical Rating Scale for Tremor Part C) outcomes between MRgFUS and unilateral DBS in the short-term (≤12 months). 38 We assessed the costeffectiveness of MRgFUS compared with standard treatments in 2 distinct patient populations: those who were ineligible for invasive neurosurgery and those who were eligible. Our analysis comparing MRgFUS with no surgery in people ineligible for invasive neurosurgery was based on a randomized, double-blind, placebocontrolled trial, 12 a study design considered to provide robust evidence.…”

Cost-minimisation model of magnetic resonance-guided focussed ultrasound therapy compared to unilateral deep brain stimulation for essential tremor treatment in Japan

“…Based on an assumption of equal efficacy, a cost-minimisation model from a Japanese healthcare payers’ perspective was used to compare MRgFUS to unilateral DBS, capturing only direct healthcare costs [15, 30–32]. All model costs were estimated using 2018 Japanese Yen (JPY) except where explicitly stated in analyses.…”

“…Evidence from a small retrospective analysis and an indirect treatment comparison (ITC) of MRgFUS and unilateral DBS with 12 months follow-up shows that these procedures provide similar relief from tremor and its associated disabilities [15, 30]. Therefore, a cost-minimisation model, which assumes equal efficacy for each included procedure, can be considered an appropriate approach for comparing the costs of MRgFUS to unilateral DBS across a 12-month time horizon.…”