Comparative Efficacy of Radioiodine Therapy With Adjunctive Thionamides vs Either Treatment Alone in the Management of Graves Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract Context Antithyroid drugs (ATDs) and radioactive iodine (RAI) are the main nonsurgical modalities for Graves disease, but there is no agreement on the optimal approach for utilizing these 2 alternatives, either individually or in combination. Objective This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the success (hypothyroidism/euthyroid) and failure (hyperthyroidism/relapse) of adjunctive (pre-RAI/post-RAI/both) and monotherapy with ATDs in Graves disease. Methods PubMed, CENTRAL, Scopus, and Web of Science were searched to December 2023 for RCTs on adjunctive ATDs with RAI or ATDs monotherapy in adults. Pooled relative risks were estimated using a random-effects model. Certainty of findings was assessed with GRADE. Results We included 21 RCTs (1914 participants). Adjunctive ATDs showed no significant effect on success (RR: 0.96, 95% CI: 0.91-1.01) or failure (RR: 1.17, 95% CI: 0.97-1.42) rate (moderate GRADE) but increased the chance of euthyroid state and reduced hypothyroidism (RR: 0.67, 95% CI: 0.50-0.90) compared to RAI. ATDs monotherapy vs RAI with adjunctive ATDs showed no significant difference in resolving hyperthyroidism (RR: 0.93, 95% CI: 0.84-1.02). Propylthiouracil with RAI was associated with reduced likelihood of success (RR: 0.81, 95% CI: 0.69-0.96). Conclusion ATDs do not significantly affect the success or failure rates of RAI therapy, particularly in long-term follow-up, but they may improve euthyroid outcomes and reduce hypothyroidism. Long-term ATD monotherapy showed no significant difference compared with RAI in resolving hyperthyroidism; however, additional long-term trials are needed to confirm these findings. Management of Graves disease requires individualized physician-patient decisions.