Autoimmune thyroid disease following alemtuzumab therapy for multiple sclerosis (#240)
The humanised anti-CD52 monoclonal antibody Alemtuzumab induces an immune mediated depletion of CD4+T cells, and has been shown to be superior to interferon β-1a in treating relapsing-remitting multiple sclerosis (RRMS), with reduction in relapse rates and improved disability scores. However, a significant proportion of patients develop new autoimmunity as a result of treatment, and the thyroid gland appears to be particularly susceptible.
A 38 year-old woman with RRMS was treated with two courses of Alemtuzumab 12 months apart. Pre treatment thyroid function tests were normal and auto-antibodies were not detected. 12 months after the 2nd course of Alemtuzumab she developed symptoms of hyperthyroidism, and thyroid function tests showed TSH <0.02 mIU/L, FT4 41.0 pmol/L, T3 15.4 pmol/L. TSH receptor antibody was elevated at 8 U/L. Thyroid technetium scan revealed diffusely increased tracer trapping consistent with Graves’ Disease. She was commenced on Carbimazole therapy.
Novel autoimmune thyroid disease is reported in up to a third of RRMS patients treated with Alemtuzumab. Graves’ Disease is most common, with cases of thyroiditis and hypothyroidism also being reported. The majority of cases are detected 12-36 months after the initial treatment dose of Alemtuzumab, indicating that the development of autoimmunity is timed with immunological reconstitution. The pathogenesis of reconstitution Graves’ Disease remains unclear, but is likely related to preferential expansion of autoreactive T cells, and high circulating baseline IL-21 levels are thought to be a predisposing factor.
As there is accumulating evidence of its superior efficacy compared to interferon β-1a, Alemtuzumab is predicted to become standard treatment for RRMS in the future. Therefore, there is likely to be an increased incidence of autoimmune thyroid disease in this population. This case highlights the need to develop standardised screening protocols to ensure prompt referral and implementation of treatment in this patient group.
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