0792 Efficacy and Temporal Trajectory of Tonic Motor Activation in Painful and Painless Restless Legs: Interim 270-Day Results from the THRIVE Study

Abstract Introduction Restless Legs Syndrome (RLS) presents in painful and painless forms, with the painful phenotype indicating a more severe clinical course. Data comparing treatment efficacy between these groups is scarce. This study analyses real-world 270-day interim efficacy and safety of tonic motor activation (TOMAC), a non-invasive high-frequency peroneal nerve stimulator, in painful versus painless RLS patients. Methods Data were pooled from the THRIVE study, a longitudinal, post-market study evaluating TOMAC effectiveness and safety in adults with primary moderate-severe refractory RLS. Baseline variables included age, sex, RLS family history, RLS age-at-onset, current RLS medications, TOMAC titrated stimulation intensity, International RLS Severity Scale (IRLS), Medical Outcomes Study Sleep Problem Index II (MOS-II), and RLS symptom days per week. Painful RLS was defined by affirmative answers to two consecutive baseline questions on the presence of unpleasant, uncomfortable, and specifically painful feelings in the legs. Primary endpoint was 270-day change in IRLS score. Secondary endpoints included changes in MOS-II score, RLS symptom days per week, and Clinical Global Impression-Improvement (CGI-I) and Patient Global Impression-Improvement (PGI-I) responder rates. The temporal trajectory (at 90, 180, and 270 days) of each endpoint was also analyzed by Mixed Model for Repeated Measures (MMRM). RLS medication changes and TOMAC safety were compared. Results The intent-to-treat population included 127 adult patients (56 painful RLS, 71 painless RLS) with moderate-to-severe, medication-refractory RLS. At baseline, painful RLS patients had more severe symptoms (mean [standard deviation] IRLS scores: 27.2 [5.3] versus 24.5 [5.7]; P=0.007) and used more dopaminergic agents (68% versus 49%; P=0.036). All other baseline variables listed above were similar. After 270 days of TOMAC, mean changes in IRLS scores, MOS-II scores, and RLS symptom days per week were similar between groups. Responder rates (CGI-I, PGI-I), RLS medication changes, and adverse event rates were similar. MMRM confirmed similar improvements for key endpoints starting at 90 days and persisting through 270 days in both groups. Conclusion This study confirms painful RLS as a more severe phenotype at baseline. However, TOMAC treatment demonstrated consistent and similar efficacy, safety, and temporal trajectory between the two phenotypes, with both maintaining significant improvements over a nine-month period. Support (if any) Sponsored by Noctrix Health.