ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2006) 11 P918

Treatment of patients with Graves’ disease and ophthalmopathy with the anti-CD20 monoclonal antibody rituximab

M Salvi1, GM Vannucchi1, I Campi1, C Guastella2, F Sbrozzi3, S Simonetta3, S Rossi4, P Bonara5, S Avignone6 & R Ratiglia3

1Institute of Endocrine Sciences, University of Milan, Fondazione Policlinico IRCCS, Milan, Italy; 2Otolaryngology, Fondazione Policlinico IRCCS, Milan, Italy; 3Ophthalmology, Fondazione Policinico IRCCS, Milan, Italy; 4Patology Department, Ospedale San Paolo, Milan, Italy; 5Internal Medicine, Fondazione Policlinico IRCCS, Milan, Italy; 6Neuroradiology, Fondazione Policlinico, IRCCS, Milan, Italy.

We are conducting an open study on the treatment of Graves’ disease (GD) and thyroid-associated ophthalmopathy (TAO) with the monoclonal antibody to CD-20, rituximab (RTX) (MabThera, Hoffman-Roche, Basel). RTX induces depletion of B cells and GD is typically a B cell dependent autoimmune disease. We present preliminary results on 7 patients with GD and TAO at different clinical stages: 3 women with newly diagnosed GD and initial TAO; 1 woman with GD and moderate-severe TAO, not responsive to steroids; 1 man with severe TAO, which appeared 12 months after thyroidectomy; one man and one woman with GD and moderately severe, active TAO on antithyroid drugs withdrawn about a month before RTX. Patients were assessed by measuring thyroid function tests, serum autoantibodies and peripheral blood lymphocytes subpopulations, by orbital imaging and thyroid ultrasound, and by ophthalmologic evaluation with the attribution of the clinical activity score (CAS). We applied a standardized protocol of 2×1000 mg RTX infusions at a 2-week interval. All but one patient attained total B cell depletion. In 6 patients with active TAO the CAS improved within 1–4 months from RTX infusion and remained low even after B cell return. In one patient submitted to thyroidectomy and orbital decompression after RTX we found B cells in the thyroid but no immune cells in the orbital tissue. She had severe TAO, high serum TRAb and a relapse of hyperthyroidism during B cell depletion. Remission of hyperthyroidism was observed in 3 patients, in one after adding methimazole (MMI), and only in 2 with normalization of serum TRAb. One patient at 3 months after RTX and no other therapy is still hyperthyroid with no change in serum TRAb. In conclusion, RTX therapy improves clinically active TAO and induces stabilization in 1–3 months. We have evidence that RTX may act by depleting the orbit of immune cells. RTX therapy does not affect hyperthyroidism in GD patients with elevated serum TRAb levels, unless MMI is added. It may induce progressive normalization of serum TRAb levels and remission of hyperthyroidism in GD patients with moderately elevated serum TRAb levels (<10 U/l).

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