Conservative Management of Hyperthyroidism Arising From Alemtuzumab Treatment in MS

Background:

Alemtuzumab is a monoclonal antibody that binds CD52 receptors on lymphocytes and monocytes causing complement-mediated lysis of these cells. Alemtuzumab has been shown to reduce both the annualized relapse rate and the rate of sustained accumulation of disability in Multiple Sclerosis when compared to Interferon therapy. However, over a third of patients treated with alemtuzumab develop novel secondary autoimmune diseases of the thyroid, in particular Graves’ disease. Previous reports of management of hyperthyroidism in this setting have included treatment with thyroidectomy and radioactive iodine.

Objectives:

To describe our experience with the management of multiple sclerosis patients who developed hyperthyroidism as a result of alemtuzumab treatment in the clinical trials (CARE MS-I & II).

Methods: not applicable

Results:

Of 7 patients who received alemtuzumab in the trials, 4 patients developed thyroid dysfunction. All presented with symptoms of thyrotoxicosis and had biochemically confirmed hyperthyroidism. In all 4 cases the degree of hyperthyroidism was moderate to severe with elevation of Free T4 and Free T3 hormones at presentation to at least 2-3 x upper limit of normal with concomitant suppression of TSH. In 2 of the 4 cases, the hyperthyroidism resolved within 4-8 weeks with no antithyroid treatment, and subsequently the patients became permanently hypothyroid.  In one case, treatment with antithyroid medication was discontinued after 4 months when the patient became hypothyroid. Only in one case was there evidence of sustained hyperthyroidism requiring continuous treatment with antithyroid medication methimazole for one year with good response.

Conclusions:

In this small case series, the majority of patients developing hyperthyroidism following treatment with alemtuzumab have a temporary course of hyperthyroidism pathognomonic of autoimmune thyroiditis which resolves quickly with minimal medical treatment.  In the case of Graves’ disease induced by alemtuzumab, conservative management with methimazole rather than aggressive treatment with surgery or RAI treatment is shown to be both efficacious and feasible.