Antithymocyte Globulin as a Second Line Therapy in Graves Orbitopathy

Single-centre, Safety and Efficacy, Open-label Study Evaluating Antithymocyte Globulin Treatment in Subjects With Graves Orbitopathy

The overall objective of the study is to evaluate the safety and efficacy of rabbit antithymocyte globulin in the treatment of Graves orbitopathy (GO) after ineffective treatment with moderate-to-high doses of glucocorticoids.

This is a prospective interventional, single-center study examining the safety and efficacy of rabbit antithymocyte globulin (rATG) in adult patients with active moderate-to-severe GO after ineffective treatment with moderate-to-high doses of glucocorticoids. All enrolled participants will receive 0.8 - 1.0 mg/kg of rATG (cumulative dose of 150-200 mg given intravenously in two or three divided doses, 24 hours apart) after premedication with methylprednisolone i.v. (in total dose of 375 mg), 1 mg of antihistaminic agent clemastine and 1000 mg paracetamol i.v.

In order to assess efficacy and safety of the treatment, patients will be evaluated at baseline and at 6, 12, 24 and 48 weeks. Baseline and subsequent evaluation will involve medical history, physical examination, including detailed eye examination, laboratory assessment (thyroid-stimulating hormone [TSH], flow cytometry, TSH-receptor antibodies, CBC) and orbital magnetic resonance imaging (MRI).

Inclusion Criteria:

• Clinical diagnosis of Graves' disease associated with active thyroid eye disease and a clinical activity score of ≥ 3
• Euthyroid or with mild hypo- or hyperthyroidism defined as free thyroxine (FT4) and free triiodothyronine (FT3) levels less than 50% above or below the normal limits
• previous ineffective treatment (partial response, recurrence or progression of symptoms) with moderate-to-high doses of glucocorticoids (at least 4.5 g of methylprednisolone)

Exclusion Criteria:

• hypersensitivity to rabbit proteins or to any product excipients
• active acute or chronic infections
• latent tuberculosis
• leucopenia below 3000/μl
• lymphopenia below 400/μl
• thrombocytopenia below 75000/μl
• coagulation disorders
• active malignancy and pregnancy