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 patholgenesis 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 file efficacy of rituximab in patients with recurrent Graves disease. Design: We performed it 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 oil several periods after the administration of TSH. free thyroxine (FT4), 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 ill baseline to 1.4% at 26 weeks (P=0.007). Four patients With high initial FT4 levels did not respond treatment, All remaining patients had it decrease ill FT4, levels ill 26 weeks (P=0.001) and an increase ill 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 FT4 (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.