Thyroid Eye Disease: Navigating the New Treatment Landscape.
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ABSTRACT:
SUBMITTER: Dosiou C
PROVIDER: S-EPMC8078830 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC7496898 | biostudies-literature
Project description:BackgroundTeprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of active Thyroid eye disease (TED). The current study reviews its efficacy in chronic TED.MethodsIn this retrospective review, consecutive patients with chronic stable TED (>2 years), who had received ≥3 infusions of teprotumumab were included. All patients had measurements of proptosis, and calculation of the CAS and diplopia scores before and after therapy. Five-point strabismus scores were also calculated. Patients who had imaging within 4 months prior to therapy and 6 weeks post therapy underwent orbital 3D volumetric analysis.ResultsThirty-one patients met the inclusion criteria. The mean (SD) duration of TED was 81 months (56) and the mean (SD) number of infusions received by each patient was 7 (2). Mean (SD) reduction in proptosis for each study orbit was 3.5 mm (0.4) and 3 mm (0.3) for the fellow orbit. The CAS response was 90% for the study orbit and 87% for the fellow orbit. Of the 15 patients who had diplopia at baseline, 67% had a clinically significant response, while 47% had complete resolution following treatment. Following teprotumumab, mean (SD) reduction of muscle tissue was 2011 mm3 (1847) in the study orbit and 1620 mm3 (1759) in the fellow orbit. The mean (SD) reduction of fat volume was 2101 mm3 (1681) in the study orbit and 1370 mm3 (1181) in the fellow orbit.ConclusionTeprotumumab significantly reduces proptosis, inflammation, diplopia, strabismus and orbital soft tissue volume in patients with chronic TED.
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Project description:Large amounts of data emerging from experiments in molecular medicine are leading to the identification of molecular signatures associated with disease subtypes. The contextualization of these patterns is important for obtaining mechanistic insight into the aberrant processes associated with a disease, and this typically involves the integration of multiple heterogeneous types of data. In this review, we discuss knowledge representations that can be useful to explore the biological context of molecular signatures, in particular three main approaches, namely, pathway mapping approaches, molecular network centric approaches and approaches that represent biological statements as knowledge graphs. We discuss the utility of each of these paradigms, illustrate how they can be leveraged with selected practical examples and identify ongoing challenges for this field of research.
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Project description:Graves disease is an autoimmune thyroid disease classically characterised by a clinical triad consisting of hyperthyroidism, diffuse goitre, and thyroid eye disease. Thyroid eye disease is an immunologically mediated condition in which humoral immunity is thought to play a central role. Thyroid eye disease is traditionally treated with high-dose glucocorticosteroids and surgical orbital decompression. However, responses are inadequate and alternative treatment options are needed. Rituximab, an anti-CD20 monoclonal antibody, shows promise as a novel therapeutic option for thyroid eye disease. There are 43 cases of thyroid eye disease treated with rituximab in the medical literature, and larger studies are warranted to determine the long-term effectiveness of rituximab. Rituximab may represent an attractive new treatment option for thyroid eye disease, especially in the case of disease that is refractory to current treatment strategies.
| S-EPMC5123122 | biostudies-other
Project description:ContextThyroid eye disease (TED), a vision-threatening and disfiguring autoimmune process, has thwarted our efforts to understand its pathogenesis and develop effective and safe treatments. Recent scientific advances have facilitated improved treatment options.ObjectiveReview historically remote and recent advances in understanding TED.Design/setting/participantsPubMed was scanned using search terms including thyroid-associated ophthalmopathy, thyroid eye disease, Graves' orbitopathy, autoimmune thyroid disease, and orbital inflammation.Main outcome measuresStrength of scientific evidence, size, scope, and controls of clinical trials/observations.ResultsGlucocorticoid steroids are widely prescribed systemic medical therapy. They can lessen inflammation-related manifestations of TED but fail to reliably reduce proptosis and diplopia, 2 major causes of morbidity. Other current therapies include mycophenolate, rituximab (anti-CD20 B cell-depleting monoclonal antibody), tocilizumab (interleukin-6 receptor antagonist), and teprotumumab (IGF-I receptor inhibitor). Several new therapeutic approaches have been proposed including targeting prostaglandin receptors, vascular endothelial growth factor, mTOR, and cholesterol pathways. Of potentially greater long-term importance are attempts to restore immune tolerance.ConclusionDespite their current wide use, steroids may no longer enjoy first-tier status for TED as more effective and better tolerated medical options become available. Multiple current and emerging therapies, the rationales for which are rooted in theoretical and experimental science, promise better options. These include teprotumumab, rituximab, and tocilizumab. Restoration of immune tolerance could ultimately become the most effective and safe medical management for TED.
| S-EPMC9359447 | biostudies-literature
Project description:IntroductionThyroid eye disease (TED) is a rare condition involving autoimmune-mediated inflammation of the orbit and periocular structures, which can result in many debilitating symptoms. Teprotumumab, a monoclonal antibody that targets the insulin-like growth factor 1 receptor, is gaining popularity for the treatment of TED. In fact, owing to its efficacy and side effect profile, some recommend that it be considered as a first-line therapy for patients with TED. While teprotumumab is often chosen due to its efficacy and relatively favorable side effect profile compared to other treatments, there is a known risk of hyperglycemia with this mechanism of action, which is well described through clinical trials in the oncology literature. Though all cases in the clinical trial study of teprotumumab were mild, there is growing evidence that its effect on blood sugar can be more profound.Case presentationWe present a case of a well-controlled, recently diagnosed type 2 diabetic placed on teprotumumab for treatment of TED who developed life-threatening hyperglycemia. The case report provides evidence of hyperglycemic risk, as it highlights a patient's significant increase in hemoglobin A1C to 15.4 in addition to elevated serum glucose of 954 mg/dL while receiving teprotumumab.ConclusionThis case of severe hyperglycemia accentuates the need for more diligent, if not universal, glucose monitoring during teprotumumab treatment.
| S-EPMC10950356 | biostudies-literature
Project description:BackgroundThyroid eye disease (TED) is an autoimmune disorder that constitutes a major clinical and therapeutic challenge. Current treatment options for moderate-to-severe TED include immunotherapy, orbital radiotherapy and decompression surgery. Limited drugs of proven efficacy are available for the treatment of people with TED. Given the role in the pathogenesis of TED of interleukin (IL)-6 expression in adipocytes, fibroblasts and macrophages, the proposed theory is that inhibition of IL-6 by tocilizumab may be an effective treatment in TED by directly reducing the inflammatory response. In addition, there is an unmet need for a new treatment that can modify the natural course of the disease and reduce the incidence of late complications that can occur as a result of fibrosis following inflammation.ObjectivesTo investigate the efficacy and harms of tocilizumab for the treatment of people with TED.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 6); MEDLINE Ovid; Embase Ovid; LILACS BIREME; OpenGrey; the ISRCTN registry; ClinicalTrials.gov; the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and the EU Clinical Trials Register. The date of the search was 31 July 2018.Selection criteriaWe searched for trials of tocilizumab administered by intravenous infusion using any dosage regimen, compared with placebo or intravenous glucocorticoid therapy for people with TED.Data collection and analysisWe planned to use standard methods recommended by Cochrane. The primary outcome was change in TED score (as defined by investigators). Secondary outcomes included measurement of the following parameters: change in proptosis, change in extraocular motility, change in palpebral aperture measurements, number of relapses, development of optic neuropathy and change in quality of life score. We planned to measure these outcomes at three months (range two to six months) and 12 months (range six to 18 months) post-treatment. Adverse outcomes included any adverse effects identified in the trials at any time point.Main resultsNo studies met the inclusion criteria of this review. We found one randomised, placebo-controlled, double masked study (NCT01297699). This study plans to evaluate the efficacy and harms of tocilizumab administration in people with moderate-to-severe or sight-threatening graves' ophthalmopathy (GO), that had not responded adequately to treatment with intravenous corticosteroid pulses. It was completed in December 2015 and will be assessed for inclusion in the review when data become available.Authors' conclusionsThere is currently no evidence from randomised controlled trials evaluating the efficacy and harms of tocilizumab for the treatment of people with TED.
| S-EPMC6517231 | biostudies-literature
Project description:Thyroid eye disease (TED) is a complex, debilitating autoimmune disease that causes orbital inflammation and tissue remodeling, resulting in proptosis, diplopia, and in severe cases, loss of vision. TED can lead to facial disfigurement and severely impact patients' quality of life. Although the course of TED was identified over 60 years ago, effective treatment options have proved to be challenging. Current treatments such as glucocorticoid therapy and orbital radiation focus on reducing orbital inflammation. However, these therapies fail to modify the disease outcomes, including proptosis and diplopia. Recent advances in the understanding of the molecular basis of TED have facilitated the development of targeted molecular therapies such as teprotumumab, an insulin-like growth factor-1 receptor inhibiting monoclonal antibody. In recent phase 2 and phase 3 randomized placebo-controlled trials, teprotumumab rapidly achieved improvement in clinical endpoints defining TED, including improved proptosis and diplopia. Dramatic improvement in clinical outcomes achieved after teprotumumab therapy during active TED are heretofore singular and comparable only to surgical therapies achieved during the inactive phase of TED. The advent of effective medical therapy can lead to a paradigm shift in the clinical management of TED. This review will provide an overview of TED, its epidemiology, insight into the molecular biology of the disease, clinical characteristics and diagnosis, and current and emerging treatment modalities.
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Project description:Multiple myeloma is one of the most common hematological malignancies, affecting mainly elderly patients. The treatment landscape for the management of this disease has evolved significantly over the past 15 years, and a vast array of therapeutics is now available, including immunomodulatory drugs, proteasome inhibitors, histone deacetylase inhibitors, and monoclonal antibodies. As a result, deciding which drugs to use and when, and whether these should be used in a particular order or combination, can be challenging. Although combination regimens are often associated with deeper responses and better long-term outcomes than monotherapy, and are becoming the standard of care, they may result in significant incremental toxicity; hence, a sequential approach may be more appropriate for some patients. In particular, treatment choices can vary depending on whether the patient has newly diagnosed multiple myeloma, is eligible for transplant, has relapsed and/or refractory multiple myeloma, or is considered to have high-risk disease. In this review, we discuss factors to be taken into account when making treatment decisions in each of these settings. We also briefly discuss possible therapeutic strategies involving agents that may become available in the future.
| S-EPMC6334731 | biostudies-other
Project description:ObjectiveTo determine the impact of thyroid eye disease (TED) on patients in various stages of the disease.BackgroundTED is a debilitating and potentially sight-threatening inflammatory autoimmune disease that is frequently misdiagnosed. Challenging quality-of-life (QoL) issues can persist long after the active phase of disease has subsided.MethodsA 62-question survey was designed as a hypothesis-generating instrument to identify key issues confronting patients ≥18 years old with physician-diagnosed TED. Questions focused primarily on physical and emotional status, and QoL experiences in the 2 months prior to the survey. Data for individual questions are presented as summary statistics. Correlations between questions were determined using χ2 analyses.ResultsThe 443 respondents were 18 to >80 years old; >90% female, and >80% from the United States. Time since TED diagnosis ranged from <1 year to >10 years. Participants provided >500 free-form responses describing experiences of living with TED. Physical signs/symptoms were experienced by 307/443 (69%) patients. Of those responding to the QoL questions (N = 394), 53 (13%) reported symptoms improving, 73 (19%) reported symptoms worsening, and 255 (65%) reported no change in the 2 months prior to the survey. The most bothersome signs/symptoms were dry/gritty eyes, light sensitivity, bulging eyes, and pressure or pain behind the eyes. Respondents <60 years were significantly (p < 0.0001) more likely to report symptomatic TED than older patients. Of 394 respondents, 179 (45%) reported feeling depressed and/or anxious, 174 (44%) reported concern about their appearance, and 73 (19%) avoided public situations; 192 (49%) reported declines in confidence or feelings of general well-being, and 78 (20%) reported an inability to achieve goals. Activities limited by TED included reading, driving, and socializing. The proportion of respondents experiencing these negative QoL measures was higher when patients reported experiencing >5 symptoms, had been diagnosed within the last 5 years, or were <60 years of age.ConclusionsPhysical manifestations of TED impact QoL for patients through all phases of the disease. It is essential that physicians and healthcare professionals become more familiar with patient experiences such as those described here to better help patients manage their disease.
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