BACKGROUND
Graves’ disease is the most common cause of hyperthyroidism in the United States. It is an autoimmune condition and occurs when the body develops antibodies that attack and turn on the thyroid. These antibodies are known as thyroid stimulating immunoglobulins, or TSI. Treatment options include antithyroid drugs (ATDs), radioactive iodine and surgery. ATDs may affect the autoimmune process and cause the Graves’ disease to go into remission. In general, when patients are treated with ATDs for 1 to 3 years, rates of remission are generally 20 to 30%.

Rituximab is a monoclonal antibody that suppresses an overactive immune response and has been shown to be effective in treating other autoimmune diseases such as rheumatoid arthritis. Several clinical trials using Rituximab for adult patients with Graves’ disease have been performed, but there were no reports of its use in young patients. In the current study, disease remission and treatment safety were evaluated in young patients with Graves’ disease when Rituximab was administered together with ATDs.

THE FULL ARTICLE TITLE
Cheetham TD et al 2022 Adjuvant rituximab— Exploratory trial in young people with Graves disease. J Clin Endocrinol Metab 107:743–754. PMID: 34687316.

SUMMARY OF THE STUDY
This study was phase 2 trial, meaning it was a small study testing safety and effectiveness prior to moving to large scale trials (phase 3). A total of 27 patients diagnosed with Graves’ disease between the ages of 12 and 20 years were enrolled within 6 weeks after the initiation of ATDs (carbimazole and propylthiouracil). After a single 500-mg intravenous dose of Rituximab, the ATDs were titrated according to thyroid function and were stopped at 12 months. Remission outcomes were assessed at 24 months. If patients were still hyperthyroid at 12 months, ATD therapy was continued. Participants were reviewed and had laboratory blood tests at week 4 after the end of Rituximab therapy and thereafter at regular intervals.

The proportion of Graves’ disease patients in remission at 24 months was 48% (13 of 27). At 12 months, the daily carbimazole dose was less than 5 mg in 21 of 27 participants. There were no differences in the time taken for serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations to normalize between the remission group and the relapse group. There were no serious adverse effects as the Rituximab was well tolerated.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study shows that adding a single dose of Rituximab to ATD therapy in patients with Graves’ disease may increase the likelihood of remission without severe side effects in young patients. This is an important finding and larger, phase 3, trials are warranted.

— Alan Farwell, MD

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