BACKGROUND
Graves’ disease is an autoimmune condition in which the body produces antibodies that bind to the TSH receptor on thyroid cells and turn it on (thyroid hormone receptor antibodies, TRAb). Some of these TRAbs stimulate the thyroid gland to grow excessively and to make too much thyroid hormone. Additionally, TRAbs can cause swelling of the muscles behind the eyes, a condition known as thyroid eye disease (TED), which can result in the eyes bulging out. TED affects appearance and vision. Severe cases can lead to permanent vision loss. Currently, treatments for Graves’ disease focus on reducing thyroid hormone production using medications called anti-thyroidal drugs or by surgery or radioactive iodine therapy to remove or destroy the thyroid gland. Considering the impact that TRAbs have on both hyperthyroidism and TED in Graves’ disease, therapies aimed at lowering these antibody levels could present a new treatment strategy.

A new drug called Batoclimab works by blocking a receptor called FcRn (neonatal fragment crystallizable receptor), which is found on many cells in the body. By blocking FcRn, Batoclimab decreases levels of antibodies, particularly IgG antibodies, in the body. Since TRAb is an IgG antibody, Batoclimab may be effective in treating Graves’ disease. This article summarizes the initial two studies investigating the use of Batoclimab in treating both Graves’ hyperthyroidism and Graves’ eye disease.

THE FULL ARTICLE TITLE
Kahaly GJ, Dolman PJ, Wolf J, et al. Proof-of-concept and randomized, placebo-controlled trials of an FcRn inhibitor, batoclimab, for thyroid eye disease. J Clin Endocrinol Metab 2023;108(12):3122-3134

SUMMARY OF THE STUDY
The article discusses two studies. The first was a trial to test the safety, tolerance, and effects of Batoclimab. A total of 7 participants aged 18 years or older with Graves’s disease and moderate to severe TED were given 680 mg of Batoclimab for 2 weeks, followed by a weekly 340 mg injection under the skin for 4 weeks. The researchers observed that levels of TRAb decreased by about 60% after 3 weeks but began to increase back toward their original levels after the last injection. Additionally, three patients showed signs of improvement in their eye condition. Notably, no severe adverse events were reported during the trial.

The second study was a double-blind clinical trial, meaning that neither the patient nor the researcher know which patients got the drug vs a placebo. A total of 65 patients were randomized to receive weekly subcutaneous injections of batoclimab (680mg, 340mg, or 255 mg) or a placebo. In addition to measuring antibody and thyroid hormone levels, the participants also underwent CT scan of their eyes to assess for improvement in TED. Similar to the first study, this one also found a decrease in TRAb levels, especially with the highest dose. Some patients who received the highest doses of batoclimab saw improvements in their TED symptoms, but overall, there wasn’t a clear difference in TED improvement between those who took batoclimab and those who took the placebo by the time the researchers finished analyzing the data after 12 weeks.

Although this study didn’t specifically focus on thyroid hormone levels, they did notice that the levels decreased in the groups that received batoclimab. However, the trial had to be stopped early because patients who received batoclimab experienced a significant increase in their LDL cholesterol levels, often referred to as “bad cholesterol”. Fortunately, LDL levels returned to normal after the patients stopped taking the drug.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
These are the first trials evaluating an innovative treatment for Graves’ disease. Blocking the body’s FcRn receptors reduces TRAb levels among patients with Graves disease. While the findings are preliminary and do not permit definitive conclusions, they suggest that using the Batoclimab to inhibit the FcRn receptor may improve TED and hyperthyroidism. However, due to the premature stopping of the study, numerous uncertainties remain, particularly regarding the effects of the drug on LDL cholesterol levels. Further studies focusing on TED and Graves’ hyperthyroidism are currently underway and will hopefully answer many of these outstanding questions.

— Philip Segal, MD

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