Antithyroid drug regimen for treating Graves' hyperthyroidism

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Abstract
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. To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Randomised and quasi‐randomised trials of antithyroid medication for Graves' hyperthyroidism were used. Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. Twenty‐three randomised trials involving 3115 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow‐up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the titration block‐regimen, longer duration therapy (18 months) had significantly fewer relapses (37% vs 58%) than six month therapy (Odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi‐randomised trial using the block‐replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR = 0.75, 95% CI 0.39 to 1.43). Twelve trials examined the effect of block‐replace versus titration block‐regimen. The relapse rates were similar in both groups at 51% in the block‐replace group and 54% in the titration block‐group (Peto OR = 0.86, 95% CI 0.68‐1.08). Participants reporting rashes (10% versus 6%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the block‐replace group compared to the titration block‐group respectively. 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 were not significant (Odds ratio = 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 with relapse rates being 31% (88/282) with thyroxine and 29% (82/284) with placebo (Peto OR = 1.15, 95% CI 0.79 to 1.67). The evidence (based on four studies) suggests that the optimal duration of antithyroid drug therapy for the titration block‐regimen is 12 to 18 months. The six month block‐replace regimen was found to be as effective as the 12 month treatment in one quasi‐randomised study. The titration block‐(low dose) regimen had fewer adverse effects than the block‐replace (high dose) regimen and was no less effective in trials (based on 12 trials) of equal duration. Continued thyroxine treatment following initial antithyroid therapy does not appear to provide any benefit in terms of recurrence of hyperthyroidism. The incidence of hypothyroidism was not reported and there were no deaths reported in the study populations.

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