Graves’ Disease May Develop in Response to Multiple Sclerosis Treatment

With Jerome M. Hershman, MD

A biologic drug, alemtuzumab, prescribed for relapsing-remitting MS often causes Graves' disease, requiring close monitoring to detect and manage the hyperthyroidism,1researchers warn in the face of mounting evidence.

Lemtrada (alemtuzumab), a monoclonal antibody, considered very effective in reducing the risks of disability that arise with remitting-relapsing multiple sclerosis (MS). However, patients are cautioned to be aware that this medication, while very beneficial in managing symptoms of active MS, often causes a thyroid condition known as Graves' disease,1 according to findings published in the Journal of Clinical Endocrinology and Metabolism.

Treatment for multiple sclerosis produces hyperthyroidism in most women.

The results of this study support earlier reports, say Pariani et al, a team of researchers from the United Kingdom. These investigators followed 248 patients under treatment for active multiple sclerosis for up to 20 years.

The patients who received alemtuzumab demonstrated better long-term outcomes than those receiving the other common MS drug treatment of choice: B-interferon.The development of autoimmune hyperthyroidism occurred in up to 40.7% of patients; with both conditions arising most often in women.1

Graves’ Disease: Common, Serious Consequence of MS Treatment

While the drug is highly effective at managing the symptoms and reducing the risks the arise with MS, there is a growing consensus that patients should be made aware that the development of thyroid failure can occur months or years after treatment with alemtuzumab is initiated, says Dr. Hershman, MD, who as editor-in-chief of the journal Clinical Thyroidolgy published an analysis and commentary on this findings from this study. Dr. Herhman was not involved in the study but reviewed the study findings with EndocrineWeb

In fact, Graves’ disease appears to develop as a frequent complication, as reported by the researchers who did not reply for a request for comment. They write that it often becomes necessary for patients to receive treatment for not one autoimmune condition but two ongoing chronic diseases.

Pariani and colleagues recommend regular monitoring for at least four years after the initiation of alemtuzumab begins in order to detect and treat the development of hyperthyroidism promptly.This caution comes after analyzing the data collected for more than two decades.

The 102 study participants who developed thyroid disease ranged from 20 to 60 years of age, and 78% were women.1 These MS patients received between one and five courses of the drug. For example, 55 of them were given two courses of therapy and 25 of the patients needed three courses. The patients were treated between 1993 to 2013 when the drug was being studied in other clinical trials.5,6

The researchers were able to continue following 71 patients to collect long-term data.1 Of those, 52 patients, or 73.2%, developed Graves' disease, and all needed to take antithyroid drugs initially. Another 10 individuals experienced fluctuating thyroid disease, necessitating radioactive iodine and the remaining 49 patients received a variety of treatments as met their individual needs. 

Most MS-Treated Patients Developed Hyperthyroidism

"Contrary to the published literature, we recorded frequent occurrences of [Grave’s disease] that required definitive or prolonged ATD [antithyroid drug] treatment,"1 write the researchers.

During the time the patients were followed, 102 of the 248 men and women developed thyroid problems, with more than 71% developing Graves' disease.1 The condition came on after a median of 17 months (half longer, half in less time) after the last dose of alemtuzumab. Most individuals, in fact, 89%, developed thyroid complications within three years of their last treatment for MS.

“The complication should not be taken lightly,” Dr. Hershman, MD, tells EndocrineWeb. 

"Patients taking [Lemtrada] for MS commonly develop overactive thyroid function," he says. Those patients who have prescribed this drug, he says, should be very concerned and ought to be sure their physician is aware of the risk.

"Patients on alemtuzumab need ongoing monitoring of thyroid function by their doctors," Dr. Hershman says. He calls the possibility of thyroid problems with the drug's use ''a significant possibility."

Background on Lemtrada, the Preferred Drug Treatment for MS

Lemtrada (alemtuzumab) received Food and Drug Administration approval in the United States in 2014 for use in patients who have failed to respond to at least two other drug therapies.2

Manufactured by Genzyme Corporation, Lemtrada is a prescription monoclonal antibody drug that is delivered intravenously to treat adults with the active form of multiple sclerosis known as relapsing-remitting. It's typically used in those individuals who have tried two or more MS medicines that have not worked adequately, according to the drug manufacturer.

The medicine is typically given to patients by infusion in two courses—first on five consecutive days, then a year later three more doses are given. This therapeutic approach has been approved for use in the management of relapsing-remitting (active) multiple sclerosis in more than 65 countries.

Sanofi Genzyme is clear in its product information about potentially serious side effects, such as autoimmune disorders.  

Officials at Genzyme also reviewed the study findings. In a statement, the company said: "In alignment with the authors’ conclusions, we'd like to highlight Lemtrada's favorable benefit-risk profile." The medication, according to the company, is effective at treating the MS without the need for lifelong treatment.

The company's product information indicates different percentages for commonly reported side effects that differ from that reported by the study authors.2 According to the package insert,''thyroid endocrine disorders including autoimmune thyroid disorders have been observed in 36.8% of patients treated with Lemtrada 12 mg in the clinical trial in MS with a median of 6.1 years (maximum 12 years) of follow-up from the first Lemtrada exposures.'' The company reports the most side effects were mild to moderate in severity, including rash and a change in heart rate.7

In the company statement, a spokesperson also points out the one possible study limitation may be that patients were recruited and treated only at two locations, in Cambridge and Cardiff, so additional research may be needed to confirm the link between the treatment of multiple sclerosis with alemtuzumab and the onset of Graves’ disease in other populations.7

Expert Clinical Recommendations for Patients with MS

To explain the link between the drug and thyroid issues, Dr. Hershman tells EndocrineWeb: "The drug causes a change in the immune system so that it activates the thyroid gland and causes hyperthyroidism."

If you have multiple sclerosis and choose to take the drug after discussing the options with your doctor, ongoing monitoring of your thyroid function tests is crucial, he says.

With regular follow-up, according to Dr. Hershman, thyroid problems can be caught early and ''can be treated effectively." And, he adds, in some cases the hyperthyroidism is mild, and may go away in time.

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