Autoimmune Thyroid Disease in the Use of Alemtuzumab for Multiple Sclerosis: A Review.

Abstract

Objective: The monoclonal antibody alemtuzumab has been demonstrated to reduce the risks of relapse and accumulation of sustained disability in multiple sclerosis (MS) patients when compared to ߭interferon. The development of autoimmune diseases, including thyroid disease, has been reported in the literature with a frequency of 20 to 30%. In this article, we describe 4 cases of alemtuzumab-induced thyroid disease in patients with MS. We also performed a systematic review of the available literature. Methods: Four patients who had received alemtuzumab for MS and subsequently developed thyroid dysfunction are presented. We compared our patients' clinical courses and outcomes to established disease patterns. We also undertook a systematic review of the published literature. Results: All 4 patients presented with initial hyperthyroidism associated with elevated thyroid-stimulating hormone (TSH) receptor antibodies (TRAb). In 2 cases, hyperthyroidism did not remit after a total of 24 months of carbimazole therapy, and they subsequently underwent subtotal thyroidectomy. The third case subsequently developed biochemical hypothyroidism and required thyroxine replacement, despite having a markedly raised initial TRAb titer. Autoimmunity following alemtuzumab therapy in MS appears to occur as part of an immune reconstitution syndrome and is more likely in smokers who have a family history of autoimmune disease. Conclusion: Management of alemtuzumab-induced thyroid disease is similar to the management of "wild-type" Graves' disease. The use of alemtuzumab in this setting will necessitate close monitoring of thyroid function and early intervention when abnormalities are developing.