Teprotumumab 500mg powder for solution for infusion vials

Abstract Context Teprotumumab and/or intravenous methylprednisolone (IVMP) are first-line treatments for thyroid eye disease (TED)/Graves’ orbitopathy. Direct comparisons of these treatments on Graves’ Orbitopathy Quality of Life Questionnaire (GO-QoL) are lacking. Objective Systematic review, meta-analysis, and matching-adjusted indirect treatment comparison (MAIC) of GO-QoL improvements. Methods A literature search was performed using PubMed and Embase between inception to April 1, 2023, including studies of patients with moderate to severe active TED treated with teprotumumab or IVMP. Changes in GO-QoL scores and appearance and visual function subscales were extracted. Two teprotumumab (n = 84) and placebo (n = 87) randomized clinical trials and 5 studies with IVMP (4.5 mg/12 weeks, n = 304) were identified. MAIC compared teprotumumab/placebo by adjusting for baseline GO-QoL, diplopia, proptosis, smoking, age, and sex. Significant improvements in overall GO-QoL were observed for teprotumumab vs IVMP [mean difference (MD): 13.26; 95% confidence interval (CI): 7.44, 19.09) and placebo (MD: 12.57; 95% CI: 5.94, 19.21), but not IVMP vs placebo (MD: −2.06; 95% CI: −8.24, 4.12). Improvements were noted in appearance subscale GO-QoL for teprotumumab vs IVMP (MD: 7.50; 95% CI: 0.35, 14.64) and placebo (MD: 10.80; 95% CI: 3.62, 17.98) but not for IVMP vs placebo (MD: 0.91; 95% CI: −6.36, 8.18). Visual subscale GO-QoL displayed greater improvements for teprotumumab vs IVMP (MD: 17.66; 95% CI: 7.86, 27.47) and placebo (MD: 14.54; 95% CI: 6.10, 22.99), with no significant change for IVMP vs placebo (MD: −3.65; 95% CI: −12.88, 5.57). Orbital pain, teprotumumab treatment, diplopia, proptosis, and male sex were significant independent predictors of overall GO-QoL (P < .05). Conclusion This unique analysis demonstrated a more clinically meaningful improvement in the health-related quality of life, as measured by the GO-QoL, for TED patients with teprotumumab vs both the most recommended IVMP dosage and placebo.

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BACKGROUND: Thyroid eye disease (TED) is a disabling, organ-specific autoimmune disease that is a global health concern. Recently, certain biological agents have demonstrated unique advantages for the treatment of TED. Teprotumumab is an emerging biological agent used for TED treatment. This study assessed whether teprotumumab can serve as an effective and safe treatment for active TED through a meta-analysis of the literature. METHODS: We searched 4 databases (PubMed, The Cochrane Library, Web of Science, and Embase) for randomized controlled trials regarding the treatment of Graves' ophthalmopathy by teprotumumab by March 31, 2024. We screened the literature library and extracted the data according to the inclusion and exclusion criteria. RESULTS: Our study included 5 articles that involved 411 cases. Significant differences were reported in the change from baseline in proptosis (proptosis vs baseline), diplopia response at week 24, and clinical activity score of 0 or 1 at week 24 in the teprotumumab versus placebo group. The teprotumumab group reported no significant risk of adverse events or serious adverse events during the intervention. CONCLUSION: Teprotumumab significantly decreased proptosis and clinical activity score and improved diplopia response in patients with TED, with fewer adverse effects. Therefore, it is a promising biological agent. However, this conclusion should be further validated by high-quality, long-term randomized controlled trials with large sample sizes.

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Teprotumumab has shown significant efficacy in treating Thyroid Eye Disease (TED), but its adverse effects require careful management. Key reactions include hearing impairment, hyperglycemia, and potential exacerbation of pre-existing inflammatory bowel disease (IBD). Hearing impairment, likely due to inhibition of the insulin-like growth factor 1 receptor (IGF-1R), manifests as more severe sensorineural changes. Hyperglycemia results from disrupted growth hormone feedback and may be worsened by prior glucocorticoid use. Although teprotumumab does not appear to induce new diabetes cases, it can exacerbate existing hyperglycemia. Cognitive issues, infusion reactions, and other adverse effects, such as muscle cramps and weight loss, have also been observed. Management requires careful patient screening, particularly for those with histories of hearing loss, diabetes, or IBD. Further research is essential to elucidate the underlying mechanisms of these adverse effects and develop targeted preventive strategies to improve the safety and efficacy of teprotumumab in clinical practice.

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Thyroid eye disease (TED) is a complex autoimmune disorder characterized by orbital inflammation and tissue remodeling. Teprotumumab, a fully human monoclonal antibody targeting insulin-like growth factor-1 receptor (IGF-1R), represents a significant breakthrough in TED treatment. This review comprehensively analyzes the therapeutic role of teprotumumab in TED management. Mechanistically, teprotumumab inhibits the IGF-1R/TSHR signaling complex, thereby reducing orbital fibroblast differentiation and inflammatory responses. Phase II and III clinical trials have demonstrated its remarkable efficacy in reducing proptosis and improving clinical activity scores, with the benefits extending to both active and chronic TED cases. Real-world studies have validated these findings further and expanded its potential applications to various clinical scenarios, including dysthyroid optic neuropathy and steroid-resistant cases. However, several challenges remain. These include treatment-related adverse effects such as hyperglycemia and hearing impairment, with emerging evidence suggesting ethnic variations in susceptibility. The high cost of treatment poses significant accessibility barriers, while limited long-term follow-up data and potential disease recurrence necessitate further investigation. This review synthesizes the current evidence to inform clinical decision-making and highlights areas requiring additional research to optimize teprotumumab's therapeutic application in TED management.

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Graves' disease is an autoimmune thyroidopathy associated with hyperthyroidism and nonendocrine manifestations such as thyroid eye disease (TED), pretibial myxedema, and thyroid acropachy. Thyroid acropachy is an uncommon but debilitating condition, typically characterized by digital clubbing, soft tissue swelling, and periosteal new bone formation in the hands and feet. This condition often accompanies TED and dermopathy, but effective treatments remain elusive. The first documented case of thyroid acropachy successfully treated with teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R), is reported here. A 49-year-old female with a history of Graves' disease developed severe musculoskeletal symptoms, including clubbing and periosteal new bone formation. Despite initial therapies with rituximab and intravenous immunoglobulin showing limited benefit, treatment with teprotumumab, primarily prescribed for TED, led to significant clinical and radiological improvement. After completing eight cycles of teprotumumab, the patient's musculoskeletal pain resolved, clubbing regressed, and radiologic findings of periosteal bone formation diminished. This case highlights the potential of teprotumumab as a novel therapeutic option for thyroid acropachy and suggests that IGF-1R plays a crucial role in its pathogenesis. While this report presents promising results, further studies are needed to confirm the efficacy of teprotumumab in treating thyroid acropachy and better understand its long-term effects on this rare condition.

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Introduction: Thyroid eye disease (TED) is an autoimmune process characterized by extraocular muscle and orbital fat remodeling/expansion resulting in swelling, pain, redness, proptosis, and diplopia. Teprotumumab, an insulin-like growth factor-I receptor inhibitor, demonstrated improvements in TED signs and symptoms in three adequately powered clinical trials of 24 weeks duration. Here we analyze the long-term maintenance of responses with teprotumumab from these trials. Methods: A total of 112 patients who received 7 or 8 infusions of teprotumumab in the Phase 2, Phase 3 (OPTIC study), and OPTIC Extension (OPTIC-X) studies were included in this analysis. Responses, including clinical activity score (CAS ≥2-point improvement), the European Group of Graves’ Orbitopathy ophthalmic composite outcome, diplopia (≥1 Gorman grade improvement), proptosis (≥2 mm improvement), Overall (improvement in proptosis + CAS), and disease inactivation (CAS ≤1), were assessed and pooled from study baseline to week 24 (formal study) and up to week 72 (formal follow-up). Graves’ Ophthalmopathy quality-of-life (GO-QoL) scores were also assessed. Outcomes included the percentages of observed patient responses from the study baseline. Additional alternative treatments for TED were assessed as a surrogate of persistent benefit from week 24 through week 120 (extended follow-up). Studies differed in the timing of follow-up visits, and data from some visits were unavailable. Results: At week 72, 52/57 (91.2%), 51/57 (89.5%), 35/48 (72.9%), 38/56 (67.9%), and 37/56 (66.1%) of patients were responders for CAS, composite outcome, diplopia, proptosis, and Overall response, respectively. The mean reduction in proptosis was 2.68 mm (SD 1.92, n = 56), mean GO-QoL improvement was 15.22 (SE 2.82, n = 56), and disease inactivation (CAS ≤1) was detected in 40/57 (70.2%). Over 99 weeks following teprotumumab therapy, 19/106 (17.9%) patients reported additional TED therapy during formal and extended follow-up. Conclusion: The long-term response to teprotumumab as observed 51 weeks after therapy was similar to week 24 results in the controlled clinical trials. Inflammatory and ophthalmic composite outcome improvements were seen in 90% of patients with nearly 70% reporting improvement in diplopia and proptosis. Further, 82% of patients in this analysis did not report additional TED treatment (including surgery) over 99 weeks following the final teprotumumab dose.

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