Real-world effectiveness and safety of tonic motor activation therapy for refractory restless legs syndrome: 90-day outcomes from the THRIVE prospective observational study

STUDY OBJECTIVES: The purpose of the THRIVE study is to evaluate the outcomes of patients receiving tonic motor activation (TOMAC) for treatment of refractory restless legs syndrome (RLS) in real-world clinical practice. This article examines outcomes after 90 days of TOMAC treatment. METHODS: THRIVE is a multicenter, prospective, observational study that enrolled 325 patients prescribed TOMAC (Nidra) for the treatment of RLS. The indicated intent-to-treat analysis population included adults with refractory moderate-severe RLS. The primary endpoint was change in International RLS Study Group (IRLS) score. Secondary endpoints included Clinician Global Impressions-Improvement score and change in Medical Outcomes Study Sleep Problems Index II (MOS-II) score. Adjunctive RLS medications were assessed at study entry and day 90. RESULTS: A total of 232 patients met criteria for indicated intent-to-treat analysis. Change in IRLS score at day 90 was -8.4 (95% CI: -7.4 to -9.4). Clinician Global Impressions-Improvement responder rate was 64% and mean score was 2.4 (95% CI: 2.2 to 2.6). Change in MOS-II score was -12.8 (95% CI -10.3, -15.3). Reductions to adjunctive RLS medication dosage were more common than increases (19% decreased vs. 11% increased; p = .01) and were well-tolerated (mean IRLS change: -8.1; 95% CI -6.3, -9.9). There were no statistically significant predictors of effectiveness. There were no severe or serious device-related adverse events. CONCLUSIONS: In real-world clinical practice, TOMAC is safe and effective at reducing RLS symptoms and improving sleep in adults with moderate-to-severe refractory RLS. CLINICAL TRIAL: A Post-Market Study for Long-Term Effectiveness and Safety of the Noctrix TOMAC System for RLS (THRIVE); https://clinicaltrials.gov/study/NCT06076499; Registered at ClinicalTrials.gov with the identifier number NCT06076499 Statement of Significance This paper reports the 90-day results from the first real-world study to evaluate the safety and effectiveness of tonic motor activation (TOMAC) for treatment of refractory restless legs syndrome. We report that the effectiveness and safety of TOMAC is similar in real-world practice compared to controlled trials. This study had the largest sample size and the most heterogeneous patient population of TOMAC clinical trials, thereby allowing comparison of outcomes among different subgroups; we found that TOMAC is equally effective across subgroups. Furthermore, many patients were able to tolerate substantial reduction in dosage of dopamine agonists, which is of great interest given the shift away from dopamine agonists in clinical guidelines due to their risk for augmentation.