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.