Context: Graves' disease (GD) is a common thyrotropin receptor autoantibody (TRAb)-mediated disorder. Since B lymphocytes are important self-antigen presenting cells and precursors for antibody-secreting plasma cells, temporary B lymphocyte depletion with the monoclonal antibody Rituximab (RTX) might be of benefit in GD.

Objective: To investigate the effect of RTX in GD.

Design: Prospective, controlled, nonrandomized study.

Setting: Outpatients referred to a university clinic.

Patients: Twenty patients with newly diagnosed (four with relapse) untreated GD. Ten received RTX (+RTX) while ten did not (-RTX).

Intervention: The patients had received Methimazole for a median of 102 days (+RTX) and 110 days (-RTX), prior to the study. +RTX patients received 375 mg RTX/m2 i.v. on days 1, 8, 15 and 22 and all patients were withdrawn from Methimazole at day 22.

Main outcome measures: Time to relapse of hyperthyroidism and changes in autoantibody levels.

Results: Four +RTX patients remained in remission with a median followup of 705 (435-904) days, while all the -RTX patients had relapsed by day 393 (p<0.05). All of the patients in remission had initial TRAb levels below 5 (normal: <0.7) IU/l. However, none of the five -RTX patients with correspondingly low TRAb levels were in remission (p<0.01). RTX-treatment did not affect autoantibody levels to a greater extent than did MMI monotherapy. Two patients received glucocorticoids for joint pain after RTX-therapy.

Conclusions: RTX-treatment may induce sustained remission in GD patients with low TRAb levels. However, RTX did not affect autoantibody levels and seems ineffective in patients with high TRAb levels. At present, high cost, low efficacy, and potential side-effects does not support use in uncomplicated GD.