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Rituximab in relapsing Graves’ disease

K Heemstra, Endocrinology and metabolic diseases, Leiden University Medical Centre, Leiden, Netherlands
R Toes, Rheumatology, Leiden University Medical Centre, Leiden, Netherlands
J Sepers, Internal Medicine, Medical Centre Alkmaar, Alkmaar, Netherlands
A Pereira, Endocrinology and metabolic diseases, Leiden University Medical Centre, leiden, Netherlands
E Corssmit, Department of Endocrinology C4R, Leiden University Medical Center, Netherlands
T Huizinga, Rheumatology, Leiden University Medical Centre, Leiden, Netherlands
J Romijn, Department of Endocrinology, C4-R, Leiden University Medical Center, Leiden, Netherlands
J Smit, Department of Endocrinology, Leiden University Medical Center, Leiden, Netherlands

Correspondence: Karen Heemstra, Email: K.A.Heemstra{at}LUMC.nl

Abstract

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-weeks Phase II study with open-end observational extension to assess the efficacy of Rituximab in patients with recurrent Graves’ disease.

Design: We performed a prospective, 26 weeks phase II study with open end observational extention.

Methods: Thirteen patients with relapsing Graves’ disease (9 females, 4 males, age 39.5 ± 9.5 years) received 2 dosages of Rituximab 1000 mg intravenous with a 2-week interval. Before administration and on several periods after administration thyrotropin (TSH), free thyroxine (FT4), thyrotropin receptor binding immunoglobulins (TBII) and the proportion of CD19 and CD20 positive peripheral blood mononuclear cells were measured.

Results: The proportion of CD20 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 FT4 levels did not respond to treatment. All remaining patients had a decrease in FT4 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, 9 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.