Search

Thyroid eye disease (TED) is an inflammatory condition involving the periocular and orbital soft tissues, affecting most commonly patients with hyperthyroid disorders. Traditional treatments used for the active phase of the disease range from conservative lubrication for mild symptoms to systemic immunomodulating drugs for moderate-to-severe symptoms. Teprotumumab (Tepezza) is a monoclonal antibody with an inhibitory effect on insulin-like growth factor 1 and is the first Food and Drug Administration (FDA) approved targeted medical therapy for reducing the inflammatory signs and symptoms associated with TED. Two large multicenter, randomized, double-masked, placebo-controlled trials have confirmed the efficacy and safety of teprotumumab in patients with active, moderate-to-severe TED. Recent reports and publications have also demonstrated the efficacy of teprotumumab in a wider range of patients. In this review, we summarize the clinical features and pathophysiology of TED, disease course, and traditional management methods. We further detail the development of teprotumumab, the founding studies that brought it to its FDA approval, adverse events profile, and ongoing as well as future investigations. [ABSTRACT FROM AUTHOR]

PURPOSE: To examine changes in intraocular pressure (IOP) in patients with thyroid eye disease (TED) following teprotumumab. MATERIALS AND METHODS: A retrospective review of 17 patients with TED who received teprotumumab between January 2020 and September 2021 was conducted. IOP, extent of proptosis, and clinical activity score were reviewed at baseline and at 6 weeks, 12 weeks, and 24 weeks for patients undergoing teprotumumab treatment. The primary outcome measure was change in IOP, while secondary outcome measures included changes in proptosis and clinical activity score. RESULTS: Of the 17 patients (34 eyes) with TED who were treated with teprotumumab, the mean age was 50.5 years, and 15 (88%) were female. The mean baseline IOP was 20 mm Hg (range 13-28), and the mean baseline clinical activity score was 3.8 (range 0-6). Of the 34 eyes examined at baseline, examinations were repeated in 16 at 6 weeks, 26 at 12 weeks, and 8 at 24 weeks. At week 6 of treatment, mean IOP decreased by 4.9 mm Hg (P < 0.0001). At week 12 of treatment, mean IOP decreased by 4.6 mm Hg (P < 0.0001). Mean IOP was decreased at last record of follow-up by 4.9 mm Hg (P < 0.0001). CONCLUSION: Among patients with TED, teprotumumab treatment was associated with a reduction in IOP. [ABSTRACT FROM AUTHOR]

Graves' disease (GD) is characterized by thyrotoxicosis, caused by the presence of circulating thyroid stimulating antibodies (TSAb), that are determinant also in the pathogenesis of its extrathyroidal manifestations [Graves' ophthalmopathy (GO), pretibial myxedema]. T helper (Th)1 immune response prevails in the immune-pathogenesis of GD and GO, during the active phase, when Th1 chemokines, and their (C-X-C)R3 receptor, play a key role. In GD, the existing treatments are not ideal for hyperthyroidism (long-term remission with anti-thyroid-drugs only in 50% of patients; while radioiodine and surgery cause hypothyroidism). In GD, antigen-specific therapy has been recently published, with the induction of T cell tolerance via an immunization by TSH-R peptides. In GO, rituximab and drugs targeting cytokines have been evaluated. Furthermore, teprotumumab (a human monoclonal anti-IGF-1R blocking antibody) showed to be very effective in GO patients. Further researches are necessary to identify novel effective therapies targeting GD, or GO. [ABSTRACT FROM AUTHOR]

Thyroid-associated ophthalmopathy (TAO) remains a vexing autoimmune component of Graves' disease that can diminish the quality of life as a consequence of its impact on visual function, physical appearance and emotional well-being. Because of its relative rarity and variable presentation, the development of highly effective and well-tolerated medical therapies for TAO has been slow relative to other autoimmune diseases. Contributing to the barriers of greater insight into TAO has been the historical absence of high-fidelity preclinical animal models. Despite these challenges, several agents, most developed for treatment of other diseases, have found their way into consideration for use in active TAO through repurposing. Among these, teprotumumab is a fully human inhibitory monoclonal antibody against the insulin-like growth factor I receptor. It has shown remarkable effectiveness in moderate to severe, active TAO in two completed multicenter, double masked, and placebo controlled clinical trials. The drug exhibits a favorable safety profile. Teprotumumab has recently been approved by the U.S. F.D.A, and may rapidly become the first line therapy for this disfiguring and potentially blinding condition. [ABSTRACT FROM AUTHOR]

A Th1 immune-preponderance has been shown in the immunopathogenesis of autoimmune thyroiditis (AT), Graves' disease (GD) and Graves' Ophthalmopathy (GO), in which the Th1-chemokines (CXCL9, CXCL10, CXCL11), and their (C-X-C)R3 receptor, have a crucial role. Methimazole, and corticosteroids have been shown to modulate these chemokines; several efforts have been done to modulate the autoimmune reaction with other drugs, i.e. PPAR-γ, or -α ligands, or antibodies, or small molecules directed against CXCL10, or CXCR3. Antigen-specific therapy for GD, by inducing T cell tolerance through an immunization with TSH-R peptides, has been published. Drugs targeting cytokines [anti-TNFα (Etanercept), and anti-IL-6 (Tocilizumab)], and RTX (a chimeric monoclonal antibody vs. CD20) have been used in GO, with promising results. Teprotumumab (a human monoclonal anti-IGF-1R blocking antibody) has been investigated in a trial, showing it was very effective in GO patients. Still, more studies are needed for new therapies targeting autoimmune thyroid disorders. [ABSTRACT FROM AUTHOR]