Adjunctive atorvastatin in moderate-to-severe thyroid eye disease (SEMAR-TED: Structural, Biomarker Expression and Muscle endpoints of Atorvastatin): study protocol for a randomised, open-label, assessor-masked controlled trial

Background High-dose intravenous glucocorticoid remains the first-line medical treatment for active, moderate-to-severe Thyroid Eye Disease, but the disease fails to become inactive in a substantial minority, and the adjuncts recommended alongside it are neither licensed nor affordable in Indonesia. The one randomised trial of adjunctive atorvastatin, Statins for Graves' Orbitopathy (STAGO), enrolled only patients with elevated low-density lipoprotein cholesterol, at a single European centre, and assessed the orbit by clinical measures alone, without imaging. Methods Sixty adults with active, moderate-to-severe Thyroid Eye Disease at a tertiary referral centre in Yogyakarta, Indonesia, will be allocated 1:1 to intravenous methylprednisolone (500 mg weekly for six weeks, then 250 mg weekly for six weeks) with or without oral atorvastatin 20 mg daily for 24 weeks. Baseline cholesterol is neither an inclusion nor an exclusion criterion. Treatment is open-label; outcome assessors and central image readers are masked. The primary outcome is lateral rectus muscle, medial rectus muscle, superior rectus muscle, inferior rectus muscle diameter of the more affected orbit at week 24, adjusted for baseline, on standardised orbital computed tomography. Secondary outcomes include the composite ocular response used in STAGO, the clinical activity score, exophtalmos, orbital fat volume, diplopia, and transcript levels of TSH receptor, IGF-1 receptor, PDGF receptor, PI3K/AKT, miR-146a and miR-155 in blood, and in orbital tissue obtained at rehabilitative orbital decompression. Discussion To our knowledge, SEMAR-TED will be the first randomised trial of adjunctive statin therapy in Graves' orbitopathy conducted in Indonesia, the first to enrol irrespective of baseline cholesterol, and the first to take a quantitative orbital imaging measure as its primary endpoint alongside prespecified transcript outcomes. It is powered for the imaging endpoint rather than the clinical composite, and will need confirmation in a larger multicentre trial. Trial registration: Registered in ClinicalTrials.gov, NCT07762105. Registration date 13th August 2026.