Glucocorticoid Regimens for Prevention of Graves' Ophthalmopathy Progression Following Radioiodine Treatment: Systematic Review and Meta-Analysis

BACKGROUND: Glucocorticoid (GC) therapy has been shown to prevent Graves' ophthalmopathy (GO) progression following radioactive iodine (RAI) treatment. However, the optimal regimen is controversial, with studies from recent years suggesting the use of lower doses and shorter GC treatment courses. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and retrospective controlled trials comparing GC regimens versus placebo, no treatment, or other GC regimens. RESULTS: Eight trials evaluating 850 patients fulfilled inclusion criteria. In patients with preexisting GO, standard dose prednisone (0.4-0.5 mg/kg tapered over 3 months) was very effective for prevention of GO progression (OR 0.14 [CI 0.06-0.35], p<0.01) in patients with mild to moderate GO. Two studies evaluated low-dose prednisone (0.2-0.3 mg/kg for 4-6 weeks) in patients with mild GO or risk factors, but were limited by not including patients with preexisting GO in the control groups. Therefore, the two low-dose groups were evaluated using indirect comparisons with control groups matched for age and clinical activity score, showing excellent efficacy versus no treatment or placebo (OR 0.20 [CI 0.07-0.60], p=0.004) and no significant difference compared with standard dose (OR 1.7 [CI 0.52-5.52], p=0.47). In patients without preexisting GO, steroid prophylaxis had no beneficial effect (OR 1.87 [CI 0.81-4.3]), though there were insufficient data regarding patients with risk factors for GO development. GC prophylaxis had no impact on hyperthyroidism resolution (OR 1.05 [CI 0.69-1.58]), and GC side effects were common but mild. CONCLUSIONS: Current evidence supports a three-tier approach for prevention of GO progression following RAI. Standard dose prednisone is the best validated regimen and should be used in patients with mild to moderate GO who have high risk of progression, while low dose prednisone can be used in patients with mild GO, and in patients without preexisting GO who have risk factors and are selected for GC prophylaxis. Patients without preexisting GO and without risk factors should not be treated with GC prophylaxis.