Graves' disease after treatment with alemtuzumab for multiple sclerosis

Alemtuzumab, a humanized monoclonal antibody against CD52, is effective in the treatment of early relapsing-remitting multiple sclerosis (MS). Common adverse effects include an acute-phase reaction, infections and autoimmune diseases, including thyroid disorders.

Patients from two phase 3 trials (CARE MS 1 and 2, n=15) were studied in a clinical research center.

Five out of fifteen patients developed severe Graves' disease after a mean of 32 months following the first alemtuzumab treatment.

Thyroid function tests and thyroid antibodies were assessed. In addition, endocrine tests and measurement of antibodies indicative of autoimmunity were performed.

Of the five patients developing Graves' disease, four patients were initially treated with antithyroid drugs, whereas the fifth patient had mild and self-limiting hyperthyroidism. Of the four patients treated with antithyroid drugs, one is currently under medical treatment in a dose-reducing regimen, whereas three patients underwent near-total thyroidectomy 2, 12 and 16 months later. Two patients developed endocrine ophthalmopathy. Pituitary, adrenal and gonadal hormones were normal in all patients. While four out of five patients were positive for several other autoantibodies, none developed other autoimmune diseases.

Since autoimmune thyroid disease is common after alemtuzumab treatment for MS, pretreatment screening and careful follow-up may allow for early diagnosis and treatment.