Antithyroid drug regimen for treating Graves' hyperthyroidism

Background Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. Objectives To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. Search strategy We searched seven databases and reference lists. Selection criteria Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism. Data collection and analysis Two authors independently extracted data and assessed risk of bias. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. Main results Twenty-six randomised trials involving 3388 participants were included. Overall the quality of trials, as reported, was poor. None of the studies investigated incidence of hypothyroidism, changes in weight, health-related quality of life, ophthalmopathy progression or economic outcomes. Four trials examined the effect of duration of therapy on relapse rates, and when using the titration regimen 12 months was superior to six months, but there was no benefit in extending treatment beyond 18 months. Twelve trials examined the effect of block-replace versus titration block-regimens. The relapse rates were similar in both groups at 51% in the block-replace group and 54% in the titration block-group (OR 0.86, 95% confidence interval (CI) 0.68 to1.08) though adverse effects (rashes (10% versus 6%) and withdrawing due to side effects (16% versus 9%)) were significantly higher in the block-replace group. Three studies considered the addition of thyroxine with continued low dose antithyroid therapy after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups was not significant (OR 0.58, 95% CI 0.05 to 6.21). Four studies considered the addition of thyroxine alone after initial therapy with antithyroid drugs. There was no significant difference in the relapse rates between the groups after 12 months follow-up (OR 1.15, 95% CI 0.79 to 1.67). Two studies considered the addition of immunosuppressive agents. The results which were in favour of the interventions would need to be validated in other populations. Authors' conclusions The evidence suggests that the optimal duration of antithyroid drug therapy for the titration regimen is 12 to 18 months. The titration (low dose) regimen had fewer adverse effects than the block-replace (high dose) regimen and was no less effective. Continued thyroxine treatment following initial antithyroid therapy does not appear to provide any benefit in terms of recurrence of hyperthyroidism. Immunosuppressive therapies need further evaluation.