Rituximab (RTX) Therapy in Patients With Active TAO

Inclusion Criteria: * ◦Man or woman between 18-70 years TAO with CAS of ≥ 4 (less than 3 months). * Euthyroid for at least 6 weeks Exclusion Criteria: * Dysthyroid optic neuropathy (DON) * Ulcerative Keratitis * Previous treatment with steroids for TAO (do not include prophylaxis for TAO in connection with radio iodine treatment) * Previous Treatment with Rituximab (MabThera®) * Positive Hepatitis B or C serology. * Receipt of a live vaccine within 4 weeks prior RTX+MTX to randomization * History of recurrent significant infection or history of recurrent bacterial infections * Patient who may not attend to the protocol according to the investigators opinion. * Pregnancy or lactation * Significant cardiac, including significant or uncontrolled arrhythmia, or pulmonary disease (including obstructive pulmonary disease). * Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications * Concomitant malignancies or previous malignancies. * Previous active tuberculosis * Alcoholism * Alcoholic related liver disease or other chronical liver disease * Bone marrow depression with leukopenia, thrombocytopenia or significant anemia * Rheumatoid or other significant pulmonary disease * Allergy to the active substance or an…