Rituximab in relapsing Graves' disease, a phase II study.

OBJECTIVE Conventional therapies for Graves' disease, consisting of medical therapy or radioiodine are unsatisfactory, because of limited efficacy and adverse events. Interventions aimed at the underlying autoimmune pathogenesis of Graves' disease may be worthwhile to explore. We therefore performed a prospective, 26-week phase II study with open-ended observational extension to assess the efficacy of rituximab in patients with recurrent Graves' disease. DESIGN We performed a prospective, 26-week phase II study with open-ended observations. METHODS Thirteen patients with relapsing Graves' disease (9 females and 4 males, age 39.5+/-9.5 years) received 2 dosages of rituximab 1000 mg i.v. with a 2-week interval. Before administration and on several periods after the administration of TSH, free thyroxine (FT(4)), thyrotropin binding inhibitory immunoglobulins (TBII) and the proportion of CD19 and MS4A1 positive peripheral blood mononuclear cells were measured. RESULTS The proportion of MS4A1 positive lymphocytes decreased in all patients from 5.8% at baseline to 1.4% at 26 weeks (P=0.007). Four patients with high initial FT(4) levels did not respond to treatment. All remaining patients had a decrease in FT(4) levels at 26 weeks (P=0.001) and an increase in TSH levels (P=0.011). TBII decreased in all remaining patients (P=0.003). At a follow-up time of 14-27 months, nine of these patients were still euthyroid with normal FT(4) (P<0.001) and TSH levels (P=0.008). CONCLUSIONS The present study results suggest a beneficial role of rituximab in mild relapsing Graves' disease. A subsequent randomized controlled trial with rituximab is recommended.