Risk Factors for the Relapse of Graves' Disease Treated With Antithyroid Drugs: A Systematic Review and Meta-analysis

Antithyroid drugs (ATDs) are the first-line treatment for Graves' disease (GD). A common problem with ATD treatment is the high relapse rate after drug withdrawal. The goal of this study was to analyze the influencing factors for the relapse of GD patients treated with ATD by using a systematic review and meta-analysis, provide some predictive indexes for the susceptibility of GD recurrence, and then further explore some useful methods to decrease the GD relapse rate after ATD treatment.

Articles published in PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, Wan Fang, and Chinese Biomedical Literature databases before January 2019 were collected. Patients newly diagnosed with GD, who were aged >16 years, were treated with ATD. Follow-up was then conducted for at least 12 months after ATD withdrawal. Only prospective or retrospective studies were eligible. The primary end point was the recurrence of GD during follow-up. All the data from the trials were analyzed via meta-analysis and meta-regression. p values < 0.05 were considered statistically significant, and statistical heterogeneity was assessed by using I² statistics.

A total of 20 studies and 3242 patients were involved in this meta-analysis, with 1681 patients relapsed (incidence rate, 51.9%) during the follow-up time. Analysis of risk factors suggested that younger age (weighted raw mean difference [RMD], -3.51; 95% CI, -5.74 to -1.29), larger thyroid volume (RMD, 4.38; 95% CI, 1.68 to 7.08), bigger goiter size (1.94% risk; 95% CI, 0.43 to 3.46), higher free triiodothyronine level (RMD, 5.09; 95% CI, 4.42 to 5.77), and higher free thyroxine level (RMD, 4.21; 95% CI, 0.54 to 7.89) were associated with the higher relapse rate of GD. The block-replace ATD regimen (a fixed high dose of an ATD with levothyroxine supplementation to maintain euthyroidism) (risk ratio, 0.64; 95% CI, 0.52 to 0.78) exhibits a lower relapse rate than the titration regimen (an ATD used alone and dose adjusted according to thyroid function tests).

This analysis revealed that certain risk factors were associated with GD relapses such as younger age, larger goiter size or thyroid volume, and the higher free triiodothyronine or free thyroxine level in the diagnosing phase of GD. For patients with these clinical characteristics, early definitive treatment with radioactive iodine or surgery should be offered to those who are unlikely to achieve remission with ATDs only. In addition, more prospective cohort studies with different ATD regimens would help to determine the optimum ATD treatment for patients with GD. PROSPERO identifier: CRD 42019146825.