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B Lymphocyte Depletion with the Monoclonal Antibody Rituximab in Graves’ Disease: A Controlled Pilot Study

Department of Endocrinology and Metabolism (D.E.F., S.J.B., L.H.), Odense University Hospital, 5000 Odense, Denmark; Institute for Inflammation Research (D.E.F., C.H.N.), Rigshospitalet National University Hospital, 2100 Copenhagen, Denmark; and Department of Hematology (H.C.H.), Odense University Hospital, 5000 Odense, Denmark

Address all correspondence and requests for reprints to: Laszlo Hegedüs, Department of Endocrinology and Metabolism, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense, Denmark. E-mail: laszlo.hegedus{at}ouh.regionsyddanmark.dk.

Context: Graves’ disease (GD) is a common TSH receptor autoantibody (TRAb)-mediated disorder. Because 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/Design: The objective of this prospective, controlled, nonrandomized study was to investigate the effect of RTX in GD.

Setting/Patients: We studied 20 outpatients referred to a university clinic with newly diagnosed (four with relapse) untreated GD. Ten received RTX (+RTX), whereas 10 did not (–RTX).

Intervention: The patients received methimazole (MMI) for a median of 102 d (+RTX) and 110 d (–RTX) before the study. Patients in the +RTX group received 375 mg RTX/m² iv on d 1, 8, 15, and 22, and all patients were withdrawn from methimazole (MMI) at d 22.

Main Outcome Measures: We measured time to relapse of hyperthyroidism and changes in autoantibody levels.

Results: Four patients in the +RTX group remained in remission with a median follow-up of 705 d (range, 435–904 d), whereas all the patients in the –RTX group had relapsed by d 393 (P < 0.05). All of the patients in remission had initial TRAb levels below 5 IU/liter (normal, <0.7 IU/liter). However, none of the five patients in the –RTX group 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 patients with GD 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 do not support use in uncomplicated GD.

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