Study of Atorvastatin and Its Effects in Clinical and Radiological Aspects in Patients With Moderate-to-Severe Thyroid Eye Disease

The trial tests the hypothesis that, in adults with active, moderate-to-severe Graves' orbitopathy, 24 weeks of oral atorvastatin 20 mg daily added to a standard 12-week course of intravenous methylprednisolone produces a greater reduction in extraocular muscle size than intravenous methylprednisolone alone, and that any such reduction is accompanied by lower expression of TSH receptor, IGF-1 receptor, PDGF receptor, PI3K/AKT and miR-155 transcripts, and higher expression of miR-146a. The prespecified direction for miR-146a follows its reported suppression in CD4+ T cells in active disease \[26\]. Reported directions of change are compartment-specific and not unanimous, so the transcript analyses are exploratory.

Inclusion Criteria: * Age 18 to 75 years inclusive * Graves' orbitopathy graded moderate-to-severe by EUGOGO criteria * Active disease, clinical activity score ≥ 3 of 7 * Rehabilitative orbital decompression anticipated after completion of glucocorticoid therapy, on the usual clinical grounds * Able to attend weekly infusion visits and complete follow-up to week 48 * Written informed consent given * For women of childbearing potential, agreement to use effective contraception until week 24 Exclusion Criteria: * Sight-threatening disease at screening: dysthyroid optic neuropathy or corneal breakdown * Any other autoimmune disease requiring systemic immunosuppresion * Known hypersensitivity to atorvastatin or to any statin * Current or recent (within 3 months) use of any lipid-lowering drug * Any contraindication to orbital decompression * Any independent indication for lipid-lowering therapy: established atherosclerotic cardiovascular disease, more than one cardiovascular risk factor (diabetes mellitus, hypertension, obesity), or LDL cholesterol ≥ 190 mg/dL * Systemic glucocorticoid or immunosuppressive treatment for orbitopathy within the preceding 3 months * Previous orbital irradiation or orbital surgery * Alanine or aspartate aminotransferase \> 3 × upper limit of normal, or creatine kinase \> 5 × upper limit of normal, at screening * Estimated glomerular filtration rate \< 30 mL/min/1.73 m² * Pregnancy at screening (confirmed by a negative test before randomisation) or breastfeeding * Concomitant treatment with a strong CYP3A4 inhibitor * Any condition that, in the opinion of the investigator, would prevent completion of the trial