Does Immunosuppressive Therapy Improve Outcomes in Graves' Disease? A Systematic Review and Meta-Analysis

BACKGROUND: Whether the addition of immunosuppressive drugs to standard antithyroid drugs reduces the relapse risk in Graves' disease remains uncertain. PURPOSE: The aim of this study was to investigate the effects of immunosuppressive drugs on the relapse rate after a first episode of hyperthyroidism due to Graves' disease. METHODS: Based on a pre-specified protocol, PubMed (1946-July 2015), EMBASE (1947-July 2015), and Cochrane (1992-July 2015) databases were searched. The search was for (randomized) controlled trials comparing immunosuppressive drugs with a control group. PRISMA and SIGN statements were used for assessing data quality. Two reviewers extracted data, with any disagreement being resolved by consensus. Data were pooled using a random-effects model. RESULTS: The primary endpoint was relapse of disease until follow-up. Secondary endpoints included reduction of thyroid volume and decrease in thyrotropin-receptor antibody (TRAb) levels. Seven trials with 862 participants were included. Most trials were small with a moderate to high risk of bias. There were 113 relapses in 481 (23.5%) patients receiving immunosuppressive drugs compared with 225 relapses in 381 (59.1%) control patients (risk ratio for recurrence 0.55; [confidence interval (CI) 0.41-0.75]). Subgroup analyses showed similar effects for randomized trials and controlled trials (I2 0%), and for trials using corticosteroid and non-corticosteroid immunosuppressive drugs (I2 0%). Use of immunosuppressive drugs also resulted in significant reductions in thyroid volume (-10.72 mL [CI -15.59 to -5.85]) and TRAb levels (-17.01 IU/L [CI -33.31 to -0.72]). Immunosuppressive drug-related adverse effects were not systematically reported, and thus were not included in the quantitative analysis. CONCLUSIONS: Current evidence suggests a possible relevant reduction in relapse risk when immunosuppressive drugs are added to standard treatment of Graves' disease. The small number of trials with high heterogeneity in regard to treatment modalities and the lack of systematic reporting of adverse effects calls for larger, conclusive trials.