ABSTRACT
Treatment of severe Graves'ophtalmopathy (GO) is a complex therapeutic challenge and spite any efforts, about one third of patients are disappointed with the outcome of treatment. Intravenous glucocorticoids (GCIV), orbital radiotherapy, or the combination of both are most frequently used for their immunosuppressive effects. The anti-CD 20 monoclonal antibody rituximab (RTX) induces transient B-cell depletion that may potentially modify the active inflammatory phase of thyroid-associated ophtalmopathy (TAO). A preliminary study in nine patients with TAO treated with RTX and twenty patients treated with GCIV was reported by Salvi and al. All patients attained peripheral B-cell depletion after the first RTX infusion. At the end of follow-up, clinical activity score values decreased more significantly compared with GCIV. Proptosis and the degree of inflammation decrease significantly in response to RTX. Relapse of active TAO are not observed in patients treated with RTX but occurred in 10 % of those treated with GCIV. If these results are confirmed in large controlled studies, RTX may represent a useful therapeutic tool in patients with active TAO.
Subject(s)
Graves Ophthalmopathy/drug therapy , Graves Ophthalmopathy/immunology , Immunologic Factors/therapeutic use , Adult , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Murine-Derived , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Combined Modality Therapy , Drug Tolerance , Female , Glucocorticoids/therapeutic use , Graves Ophthalmopathy/radiotherapy , Humans , Immunosuppression Therapy/methods , Male , Middle Aged , RituximabABSTRACT
Thyroid hormones [predominantly 3, 5, 3 -I- iodothyronine (T3)] regulate cholesterol and lipoprotein metabolism but cardiac effects restrict their use as hypolipidemic drugs. New molecules have been developped which target specifically the thyroid hormone receptor ss, predominant isoform in liver. The first thyroid hormone agonist, called GC1, has selective actions compared to T3. In animals, GC1 reduced serum cholesterol and serum triglycerides, probably by stimulation important steps in reverse cholesterol transport. Other selective thyromimetic, KB- 2115 and KB - 141 have similar effects. Another class of thyroid hormone analogs, the thyronamines have emerged recently but the basic biology of this new class of endogenous thyroid hormone remains to better understood. Therefore, these molecules may be a potentially treatment for obesity and reduction cholesterol, triglycerides and lipoprotein (a). To date the studies in human are preliminary. Tolerance and efficacy of these drugs are still under investigation.
