Associations Among Tremor Amplitude, Activities of Daily Living, and Quality of Life in Patients with Essential Tremor.

Background: Essential tremor (ET) is a disabling syndrome consisting of tremor, primarily in the upper limbs. We assessed the correlation of The Essential Tremor Rating Assessment Scale (TETRAS) Performance Item 4 ratings of upper limb tremor with the TETRAS activities of daily living (ADL) subscale and with 2 quality of life (QoL) scales. Methods: This noninterventional, cross-sectional, point-in-time survey of neurologists(n = 60), primary care physicians (n = 38), and their patients with ET (n = 1,003) used real-world data collected through the Adelphi ET Disease Specific Programme™. Physician-reported measures (TETRAS Performance Item 4 and TETRAS ADL total) and patient-reported QoL measures (generic EuroQol-5 Dimension 5 Level [EQ-5D-5 L] and ET-specific Quality of Life in Essential Tremor Questionnaire (QUEST)) were assessed with bivariate and multivariable analyses. Sensitivity analyses were also conducted. Results: The bivariate association between TETRAS Performance Item 4 score and TETRAS ADL total score was high (Pearson r = 0.761, P < 0.001). The bivariate associations between TETRAS Performance Item 4 score and EQ-5D-5 L index score (r = -0.410, P < 0.001) and between TETRAS ADL total score and EQ-5D-5 L index score (r = -0.543, P < 0.001) were moderate. The bivariate associations between TETRAS Performance Item 4 score and QUEST total score (r = 0.457, P < 0.001), and between TETRAS ADL total score and QUEST total score (r = 0.630, P < 0.001) were also moderate. These associations were unaltered by the inclusion of covariates. Discussion: This study showed that greater tremor severity (TETRAS Performance Item 4) was positively correlated with ADL impairment (TETRAS ADL) and negatively associated with QoL (EQ-5D-5 L and QUEST). TETRAS Performance Item 4 score is a robust predictor of TETRAS ADL total score, and TETRAS Performance Item 4 and TETRAS ADL total scores were robust predictors of the 2 QoL scales. The results demonstrate the value of TETRAS scores as valid endpoints for future clinical trials. Highlights: This real-world study assessed TETRAS scores as predictors of impaired QoL in ET. TETRAS Performance Item 4 and ADL were associated with EQ-5D-5 L and QUEST. TETRAS scores may serve as valid endpoints for future clinical trials.

Validation of a New Patient-Reported Outcome Measure of the Functional Impact of Essential Tremor on Activities of Daily Living.

Background: The Essential Tremor Rating Assessment Scale (TETRAS) is a popular scale for essential tremor (ET), but its activities of daily living (ADL) and performance (P) subscales are based on a structured interview and physical exam. No patient-reported outcome (PRO) scale for ET has been developed according to US regulatory guidelines. Objective: Develop and validate a TETRAS PRO subscale. Methods: Fourteen items, rated 0-4, were derived from TETRAS ADL and structured cognitive interviews of 18 ET patients. Convergent validity analyses of TETRAS PRO versus TETRAS ADL, TETRAS-P, and the Quality of Life in Essential Tremor Questionnaire (QUEST) were computed for 67 adults with ET or ET plus. Test-retest reliability was computed at intervals of 1 and 30 days. The influence of mood (Hospital Anxiety and Depression Scale, HADS) and coping behaviors (Essen Coping Questionnaire, ECQ) was examined with multiple linear regression. Results: TETRAS PRO was strongly correlated (r > 0.7) with TETRAS ADL, TETRAS-P, and QUEST and exhibited good to excellent reliability (Cronbach alpha 95%CI = 0.853-0.926; 30-day test-retest intraclass correlation 95%CI = 0.814-0.921). The 30-day estimate of minimum detectable change (MDC) was 6.6 (95%CI 5.2-8.0). TETRAS-P (rsemipartial = 0.607), HADS depression (rsemipartial = 0.384), and the coping strategy of information seeking and exchange of experiences (rsemipartial = 0.176) contributed statistically to TETRAS PRO in a multiple linear regression (R2 = 0.67). Conclusions: TETRAS PRO is a valid and reliable scale that is influenced strongly by tremor severity, moderately by mood (depression), and minimally by coping skills. The MDC for TETRAS PRO is probably sufficient to detect clinically important change.

A Randomized Phase 2 KINETIC Trial Evaluating SAGE-324/BIIB124 in Individuals with Essential Tremor.

BACKGROUND: SAGE-324/BIIB124 is an investigational positive allosteric modulator of GABAA receptors. OBJECTIVE: KINETIC (NCT04305275), a double-blind, randomized, placebo-controlled, phase 2 study, evaluated SAGE-324/BIIB124 in individuals with essential tremor (ET). METHODS: Individuals aged 18 to 80 years were randomly assigned 1:1 to orally receive 60 mg of SAGE-324/BIIB124 or placebo once daily for 28 days. The primary endpoint was change from baseline in The Essential Tremor Rating Assessment Scale-Performance Subscale (TETRAS-PS) Item 4 (upper-limb tremor) at day 29 with SAGE-324/BIIB124 versus placebo. RESULTS: Between May 2020 and February 2021, 69 U.S. participants were randomly assigned to receive SAGE-324/BIIB124 (n = 34) or placebo (n = 35). There was a significant reduction from baseline in TETRAS-PS Item 4 at day 29 with SAGE-324/BIIB124 versus placebo (least squares mean [standard error]: -2.31 [0.401] vs. -1.24 [0.349], P = 0.0491). The most common treatment-emergent adverse events included somnolence, dizziness, fatigue, and balance disorder. CONCLUSION: These results support further development of SAGE-324/BIIB124 for potential ET treatment. © 2024 Sage Therapeutics, Inc and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.