Most Graves’ disease treated with antithyroid drugs
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Adults with Graves’ disease are more likely to receive drug treatment — despite a higher failure rate — than radioactive iodine therapy or thyroid surgery, according to findings published in Thyroid.
“We are noticing that more people with Graves’ disease are treated with antithyroid drugs than radioactive iodine or surgery; and one fourth of people treated with antithyroid drugs will receive it as long-term — more than 2 years,” Juan P. Brito, MD, MSc, principal investigator for the Knowledge and Evaluation Research Unit in Endocrinology in the division of endocrinology, diabetes, metabolism and nutrition of the department of medicine at Mayo Clinic in Rochester, Minnesota, told Healio. “A significant number of people with Graves’ disease are receiving antithyroid drugs chronically. This way of treatment was known in other countries, particularly in Asia, but unknown here in the U.S.”
Treatment choices
Brito and colleagues evaluated the frequency with which antithyroid drugs, radioactive iodine or surgery were utilized as a first-line therapy for adults with Graves’ disease (n = 4,661; mean age, 48 years; 80% women) in the OptumLabs Data Warehouse from 2005 to 2013. Drug failure was defined as participants who initiated radioactive iodine therapy or stopped taking antithyroid drugs for more than 90 days. Radioactive iodine failure was defined as retreatment, including surgery.
Among the entire cohort, 60% received antithyroid drug treatment, 33% received radioactive iodine therapy and 6% underwent surgery. The researchers found that 50% of those who received antithyroid drugs had treatment failure within a median of 6.8 months. In addition, 65% of those who had antithyroid drug treatment failure received antithyroid drug therapy again, whereas 26% went on to receive radioactive iodine therapy and 9% went on to have surgery.
The researchers also found that 7% of those who received radioactive iodine therapy had treatment failure during a median of 3.4 months and that 1% of those who underwent surgery had treatment failure during a median of 3.2 months. In addition, 56% of participants underwent repeat radioactive iodine therapy.
Failure prediction and adverse events
According to the researchers, 6% of those who underwent radioactive iodine therapy, 12% of those who received antithyroid drugs and 24% of those who underwent surgery experienced an adverse event (P < .0001).
“These results should help clinicians and patients discuss the efficacy and safety of treatment options for Graves’ disease,” Brito said. “Particularly, antithyroid drug therapy was presented as treatment option with a horizon of 2 years. Knowing that many patients are receiving antithyroid drugs for more than 2 years could help clinicians frame the idea that antithyroid drugs could turn into a chronic therapy.”
Compared with adults aged younger than 35 years, antithyroid drug treatment failure risk was reduced by 33% for those aged 55 to 64 years (HR = 0.77; 95% CR, 0.64-0.92) and by 21.2% for those aged 65 years or older (HR = 0.788; 95% CI, 0.629-0.985). Risk for drug treatment failure was also higher for black vs. white adults (HR = 1.231; 95% CI, 1.07-1.417), and risk for radioactive iodine failure was higher for women vs. men (HR = 0.549; 95% CI, 0.362-0.833).
“Predictors of treatment failure in this very large cohort suggest that young patients had a higher failure rate than older individuals. This difference might be explained by the fact that younger patients with Graves’ disease have more severe hyperthyroidism at baseline,” the researchers wrote. “This, and the novel finding of a higher rate of failure with antithyroid drugs among African American Graves’ disease patients, needs careful assessment to confirm them, and to then uncover and untangle biological and socioeconomic explanations.” – by Phil Neuffer
For more information:
Juan P. Brito, MD, MSc, can be reached at brito.juan@mayo.edu; Twitter: @doctorjuanpa.
Perspective
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David A. Cohen, MD, FACE, ECNU
This is an interesting study that looked at treatment options for Graves’ disease, comparing the effectiveness and safety of antithyroid drugs, radioactive iodine and surgery. This study is particularly useful because we don’t have answers to the question about which is the ‘best’ treatment when they are all effective. At the end of the day, we choose which treatment based on a personalized approach, using shared decision making after a discussion of the options, including the side effect profile, costs, failure rates, and the patient’s personal values and preferences. Complicating the evaluation and discussion is that there is no ‘one Graves’ disease fits all.’ Not only is there is heterogeneity in the disease severity and patient characteristics, but also in treatment availability and cost.
This study showed that antithyroid drugs are increasing in use by endocrinologists. Just as with any treatment, when we use antithyroid drugs we are concerned about their side effects, particularly liver failure, severe rash and agranulocytosis. These side effects did not appear to be major problems with the use of antithyroid medications in this study. While endocrinologists appear to be using more antithyroid drugs, they appear to be at least as safe as we thought they were, which is very reassuring. Brito and colleagues reported a 25% remission rate for patients on antithyroid drugs for at least 1 year; this reinforces that I have many patients I can keep on antithyroid drugs and not give them definitive therapy with the possibility that they may be euthyroid and medication free.
There were some especially interesting findings to me. First was the finding of a higher rate of failure with antithyroid drugs among black and younger patients with Graves’ disease. Finding out why is very important. Second, 25% of patients who underwent thyroidectomy developed hypoparathyroidism. Usually, we tell patients that the risk for permanent hypoparathyroidism is about 1%. I assume that the very high rates of hypoparathyroidism in the study was due to many of the cases being temporary, not permanent. This highlights a drawback of the study, ,in that it looked only at ICD-10 codes. In addition, new-onset Graves’ ophthalmopathy occurred at the same rate in patients who took antithyroid drugs as compared with those who underwent radioactive iodine ablation, a finding that is in conflict with prior data that show higher rates of Graves’ ophthalmopathy following radioactive iodine. Given that we don’t know baseline thyroid function tests, antibody levels or comorbidities (such as smoking), this finding may easily be a result of patients at high risk for developing ophthalmopathy choosing antithyroid drugs. One thing we still don’t know is the long-term data. This study looked at medication use; it didn’t look at cost, quality of life or patient preference.
Although Graves’ disease is a fairly uncommon disease — less than half a percent of all people — in an endocrine practice it is incredibly common. This is a helpful study because it helps the primary care and non-endocrinologist physicians understand Graves’ disease more, and also helps the endocrinologist have some reassurance about treatment of a disease we see very commonly.
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