Tocilizumab Treatment in Graves´ Ophthalmopathy (Graves´ Orbitopathy or Thyroid Eye Disease)

Thyroid orbitopathy or Graves´orbitopathy (GO) is manifested for inflammation of the orbital and periorbital soft tissues. Ten percent of patients with GO will have long-term serious eye problems.

The cause of the GO is complex. Autoreactive T cells recognize an autoantigen, the TSH receptor present in the orbit and thyroid follicular cell, secrete cytokines (IL-6), which stimulate the fibroblasts to synthesize glycosaminoglycan, which draws liquid produce periorbital edema and muscle, causing exophthalmos.

This approach suggests that inhibition of IL-6 can be an effective treatment for this problem on the basis that tocilizumab specifically binds to the receptors of the IL-6, both soluble and membrane-bound. Tocilizumab has been shown to inhibit signaling mediated for IL-6Rm IL-6Rs.

Principal Inclusion Criteria:

Patients diagnosed GO with CAS ≥ 4 and an index of severity, according EUGOGO guidelines, 1. moderately to severely or 2. sight-threatening GO, after receiving corticosteroid pulse treatment due to:

• Poor response to intravenous corticosteroid pulses Or
• Recurrence of the GO, after treatment with intravenous corticosteroids

Exclusion criteria

• Orbital decompression surgery needed immediately
• Active smoker
• Patients who could need treatment with radioactive iodine or thyroidectomy during the study
• Pregnant patient or patient who is planning to become pregnant during the study
• History of chronic recurrent or active infection
• History of intestinal ulceration or diverticulitis
• Patients with a history of chronic liver disease or liver disorders: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) above 5 times upper limit of normal (ULN)
• History of HIV, hepatitis C or hepatitis B Positive
• Neutrophil count < 0.5 × 109/L or a platelet count < 50×103/μL
• Simultaneous use or contraindications to the use of immunosuppressive agents
• A treatment with another investigational drug within four weeks of selection or five half-lives of study drug
• Cardiovascular or cerebrovascular disease clinically significant
• Uncontrolled diabetes mellitus
• Use of corticosteroids during four weeks before to inclusion period
• History of reactions or anaphylactic allergic severe human monoclonal antibodies, humanized or murine
• Uncontrolled pathologies, whose exacerbations are treated with corticosteroids