Methimazole-induced remission rates in pediatric Graves' disease: a systematic review

Objective: Comparison of studies on remission rates in pediatric Graves' disease is complicated by lack of uniformity in treatment protocols, remission definition, and follow-up duration. We performed a systematic review on remission rates in pediatric Graves' disease and attempted to create uniformity by recalculating remission rates based on an intention-to-treat analysis. Methods: PubMed and Embase were searched in August 2020 for studies on patients with Graves' disease: (i) 2 to 18 years of age, (ii) initially treated with methimazole or carbimazole for at least 18 months, (iii) with a follow-up duration of at least 1 year after cessation of methimazole or carbimazole. All reported remission rates were recalculated using an intention-to-treat analysis. Results: Of 1890 articles, 29 articles consisting of 24 patient cohorts were included with a total of 3057 patients (82.6% female). Methimazole or carbimazole was initially prescribed in 2864 patients (93.7%). Recalculation based on intention-to-treat analysis resulted in an overall remission rate of 28.8% (829/2880). Pooled remission rates based on treatment duration were 23.7, 31.0, 43.7, and 75% respectively after 1.5-2.5 years, 2.5-5 years, 5-6 years (two studies), and 9 years (single study) treatment duration. The occurrence of adverse events was 419 in 2377 patients (17.6%), with major side effects in 25 patients (1.1%). Conclusions: Using a standardized calculation, the overall remission rate in methimazole-treated pediatric GD is 28.8%. A few small studies indicate that longer treatment increases the remission rate. However, evidence is limited and further research is necessary to investigate the efficacy of longer treatment durations.