Rituximab in the treatment of thyroid eye disease: science fiction?
Lately, monoclonal antibodies directed to molecules of the immune system have become available. Rituximab (RTX) is a humanized chimeric anti-CD20 monoclonal antibody which blocks the activation and differentiation of B cells. The rationale for use in Graves' disease (GD) and orbitopathy is the potential effect on B-cell mediated immunity. Transient B cell depletion may modify the active inflammatory phase of thyroid eye disease (TED). We have studied nine patients with GD, of whom seven had active TED and two only lid signs. All but one patients showed both CD20+ cells and CD19+ cells depletion with the first RTX infusion, while one had persistent 3-5% CD19+ cells. RTX was well tolerated and only minor side effects were reported in three patients at first infusion. Circulating antithyroglobulin, antithyroperoxidase and anti-TSH receptor antibodies did not change significantly and did not correlate to CD20+ depletion. The clinical activity score value was 4.7+/-0.5 before therapy and 1.8+/-0.8 at the end of follow-up (P<0.0001). Proptosis decreased after RTX in both patients with active TED (P<0.0001) and those with lid signs (P<0.003). The degree of inflammation (NOSPECS Class 2) decreased (P<0.001). We did not record disease relapse at any time during follow-up, even after B cell return in peripheral blood. The results of this open trial on rituximab in TED suggest that the drug is effective in improving the disease clinical course.
Institute of Endocrine Sciences, University of Milan, Milan, Italy. mariomich@lombardiacom.it
Mario
M
Salvi
Guia
G
Vannucchi
Irene
I
Campi
Paolo
P
Beck-Peccoz
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D049970:Graves Ophthalmopathy / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D012720:Severity of Illness Index; D013960:Thyroid Function Tests; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D005938:Glucocorticoids; D000069283:Rituximab