Real-world Evidence of Efficacy, Use, and Discontinuation of Pharmacotherapies for the Treatment of Essential Tremor (P3-3.006)

To conduct a literature review using real-world evidence on the most common pharmacotherapies used in treating essential tremor (ET). ET is among the most common movement disorders in the US. Current treatments include pharmacological treatments and surgical interventions, though many patients continue to lack adequate tremor control. Syntheses of published real-world evidence on ET pharmacotherapies are lacking. We conducted a comprehensive literature review of English-language studies published between 1966-2022 using PubMed. The review targeted non-clinical trial studies of adults with ET evaluating propranolol, primidone, gabapentin, and/or topiramate, and reporting at least upper limb tremor efficacy, safety/adverse events, tolerability, and/or treatment patterns. Studies reporting ≤10 subjects were excluded. We identified 236 studies. Following title and abstract screening, 75 full-text studies were assessed, with 15 included in data extraction. Patient- or clinician-validated scales were used in 2/15 studies. Activities of daily living and quality of life outcomes were not commonly reported. Up to 81% and 55% of patients used propranolol and primidone, respectively. Gabapentin (30%) and topiramate (20%) were used less frequently. Though clinical response definitions varied, propranolol demonstrated response in 37-56% of patients, and primidone in 43-55% of patients among studies with ≥50 evaluable patients. Approximately one-quarter of patients reported responding to gabapentin or topiramate. Discontinuation rates varied widely across studies, from 10-70% for both propranolol and primidone. Gabapentin and topiramate had discontinuation rates from 26-86% and 26-58%, respectively. Usage, efficacy, and discontinuation were not characterized by line of therapy (i.e. initial vs subsequent treatments) in the assessed studies. Currently available ET pharmacotherapies may not provide adequate efficacy for many patients, highlighting substantial unmet need. We identified several gaps in the published evidence base, including evaluation of commonly-used ET medications by line of therapy and reporting on validated measures to enable comparisons to new ET pharmacotherapies. Disclosure: Ms. Gerbasi has received personal compensation for serving as an employee of Sage Therapeutics, Inc.. Ms. Gerbasi has stock in Sage Therapeutics. Ms. Gerbasi has received intellectual property interests from a discovery or technology relating to health care. Ms. Tu has received personal compensation for serving as an employee of Medicus Economics, LLC. Mrs. Chertavian has nothing to disclose. Miss Nejati has received stock or an ownership interest from Biogen. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acorda Therapeutics. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal Pharmaceuticals. Dr. LeWitt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for US WorldMeds LLC. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyowa Kirin Inc. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe-NeuroDerm Neuropharma. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bukwang Pharmaceuticals. Dr. LeWitt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. Dr. LeWitt has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for CLINICAL NEUROPHARMACOLOGY.