Antithymocyte Globulin as Second-Line Therapy in Graves Orbitopathy—Preliminary Results From a Prospective Single-Center Study

Abstract

ObjectiveManagement of Graves’ orbitopathy remains a challenge. Our previous case report has shown promising results for rabbit antithymocyte globulin (rATG) in the treatment of Graves’ orbitopathy.DesignWe present the response of 7 individuals with active moderate-to-severe steroid-resistant Graves’ orbitopathy to rATG, representing preliminary results from a prospective single-center study.MethodsrATG was administered intravenously at a dose of 0.8–1.0 mg/kg daily (cumulative dose of 150–200 mg). The primary outcome measures at weeks 24 and 48 were ≥2-point reduction in Clinical Activity Score from baseline, a proptosis response, a diplopia response, and improvement of distant best-corrected visual acuity and mean retinal sensitivity. Key secondary outcomes included stabilization of ganglion cell complex thickness, a decrease of retinal nerve fiber layer in OCT, and a reduction in CD4/CD8 ratio and TRAb at 48 weeks.ResultsAn improvement in clinical activity score was observed in all patients, with disease inactivation in 3 cases. Proptosis reduction equal to or greater than 2 mm was noted for 8 of 10 eyes. Diplopia improved in three of 6 patients. There was an improvement in best-corrected visual acuity (from 0.69 to 0.78) and mean retinal sensitivity (from 20.8 to 23.5 dB). In addition, there was a long-lasting improvement in CD4/CD8 ratio in 6 patients. Two patients experienced adverse events (influenza and serum sickness).ConclusionrATG therapy offers a long-lasting improvement in moderate-to-severe steroid-resistant Graves’ orbitopathy with improvement in functional vision (reduction of diplopia, improvement of visual acuity, retinal sensitivity, and VEP pattern). The therapy is well-tolerated.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT05199103.

Evolution of Graves’ Disease during Immune Reconstitution following Nonmyeloablative Haploidentical Peripheral Blood Stem Cell Transplantation in a Boy Carrying Germline SAMD9L and FLT3 Variants

“…Alternatively, Graves’ disease may develop after aplastic anemia, with different mechanisms having been proposed [ 24 , 25 , 26 , 27 ]. For example, rATG, which has proven effective in treating steroid-resistant Graves’ orbitopathy [ 28 ], has been implicated in promoting the development of Graves’ disease following treatment for aplastic anemia with and without HSCT [ 24 , 26 ]. Adoptive transfer of a pathogenic clone from a donor suffering Graves’ disease [ 6 , 7 , 8 ], as well as the process associated with GVHD [ 9 ], have been postulated as plausible mechanisms by which Graves’ disease evolves upon allogeneic HSCT for aplastic anemia.…”

Restoration of vision by combined experimental antithymocyte therapy, and orbital radiation with high-dose steroids for severe, acute, steroid-refractory, congestive thyroid orbitopathy

“…In addition, ATG in vitro induces apoptosis of naive plasma B cells and plasma cells [ 2 ], inhibits the secondary immune response by memory B cells via T-cell modulation, and induces regulatory T cells during immune reconstitution [ 3 ]; hence, it may suppress B cells and antibodies production. Experimental studies showed a positive impact of ATG in the management of active steroid-resistant GO [ 4 , 5 ].…”