Sirolimus for Graves' Orbitopathy (GO) (SIRGO)

This is an interventional treatment trial for Graves Ophthalmopathy Read More

Inclusion Criteria:

1. Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
2. A diagnosis of Graves' disease based on the presence of hyperthyroidism (either untreated or treated with antithyroid drugs) associated with detectable anti-thyrotropic hormone (TSH) receptor autoantibodies (TRAb). Patients must be euthyroid under control on stable medical regimen and every effort will be made to maintain the euthyroid status for the entire duration of the clinical trial
3. A moderate-to-severe GO, defined as the presence of at least one of the following criteria: an exophthalmos ≥2 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm
4. Active GO: CAS (4) ≥2 out of 7 points in the most affected eye
5. GO duration ≤18 months
6. Male and female patients of age: 18-75 years
7. Creatinine values within the reference range
8. Indexes of liver function (AST, ALT, γGT, alkaline phosphatase, total and direct bilirubin) within the normal range
9. Normal blood count, absence of diseases of hematopoiesis
10. Women of childbearing potential (WOCBP, namely not in menopause or in menopause since less than two years; in all other instances women will be considered as non-WOCBP) and men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year (as indicated in Appendix) for at least 6 and 7,5 months, respectively, after the last dose of the investigational drug (see also 2014_09_HMA_CTFG_Contraception.pdf, namely the "2014 CTFG Reccommendtions related to contraception and pregnancy testing in clinical trials")
11. Compliant patients, regular follow-up possible

Exclusion Criteria:

1. Optic neuropathy
2. Treatment with glucocorticoids, other immunosuppressive drugs or selenium for the last three months
3. Previous surgery or radiotherapy for GO
4. Radioiodine treatment for hyperthyroidism over the last 3 months, as it can affect GO
5. Contraindications to Sirolimus: hypersensitivity to the active substance or to any of the excipients; use of medications interfering with the pharmacokinetic and/or pharmacodynamic properties of rapamycin (e.g. CYP3A4 inhibitors or inducers; see "prohibited therapies")
6. Contraindications to GC: hypersensitivity to the active substance or to any of the excipients; uncontrolled hypertension, uncontrolled diabetes; history of peptic ulcer; urinary infections, glaucoma, systemic fungal infections, systemic infections unless appropriate therapy is employed, idiopathic thrombocytopenic purpura, cerebral edema associated with malaria.
7. Use of medications interfering with GC or increasing the risk of GC-related adverse events (see prohibited therapies)
8. Pregnant or lactating females as determined by positive serum or urine HCG test at baseline
9. Acute or chronic liver disease
10. Relevant malignancies
11. Current and/or previous diseases of hematopoiesis
12. Recent (≤1 year) history of alcoholism or drug abuse
13. Mental illness that prevent patients from comprehensive, written informed consent