Small Dose of Rituximab for Graves Orbitopathy: New Insights Into the Mechanism of Action

Endocrine Unit, Department of Medical Sciences, University of Milan, Italy.
Archives of ophthalmology (Impact Factor: 4.4). 01/2012; 130(1):122-4. DOI: 10.1001/archopthalmol.2011.1215
Source: PubMed
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    ABSTRACT: The contribution of B-cells to human autoimmune disease has recently been underscored because of the therapeutic benefit of B-cell depleting therapies. B-cells are involved in the production of autoantibodies, and in CD4+ T-cell activation, control of T-cell function, and inflammation through cytokine production. B-cells are also important antigen-presenting cells. Rituximab (RTX) has been used off-label in various autoimmune disorders and has been shown to effectively deplete mature and memory CD20+ B-cells, but not long-lived plasma cells. The rationale behind the use of RTX in Graves' disease (GD) and Graves' orbitopathy (GO) relies on its putative effect on pathogenic autoantibodies causing hyperthyroidism. RTX in patients with active GO has been shown to have a significant effect on the inflammatory activity and severity of GO. However, caution is suggested before proposing RTX as a novel therapeutic tool in this disease until randomized controlled trials are available. Should preliminary observations be confirmed, an optimal strategy for controlling the progression of GO would be to pursue B-cell depletion shortly after diagnosis, rather than only as an alternative therapeutic option when standard immunosuppression has failed.
    No preview · Article · Dec 2011 · Endocrinology
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    ABSTRACT: The management of thyroid eye disease (TED) remains a therapeutic challenge. The current established therapies are unsatisfactory in one-third of the patients and have many limitations. Rituximab (RTX) is a CD20+ B-cell-depleting monoclonal antibody approved for the treatment of non-Hodgkin lymphomas, chronic lymphocytic leukemia, and rheumatoid arthritis. The early experience with RTX suggests that it is a promising alternative therapy for TED. Rituximab may compare favorably to the conventional glucocorticoid therapy and causes less collateral damage than retrobulbar orbital radiation and decompression surgery. In addition, the preliminary studies on RTX's proposed mechanism of action have revealed new insights into the pathogenic role of B-cells in TED. We summarize the current literature on the clinical application of RTX in TED and discuss its putative mechanisms of action.
    No preview · Article · Dec 2012 · Survey of Ophthalmology
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    ABSTRACT: Mild to moderate forms of orbitopathy are common in auto-immune thyroid diseases, whereas severe forms are rare. Euthyroidism restoration, no smoking, and ocular local lubricants are necessary for all the patients. In case of mild orbitopathy, treatment by selenium is now indicated. Active forms of thyroid orbitopathy are better treated by IV steroids. Surgery is indicated in optic neuropathy resistant to steroids and in sequellar forms of the disease.
    No preview · Article · Jan 2013 · Revue médicale suisse
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