Search

Context: Teprotumumab, which targets the insulin-like growth factor-1 receptor, is the only drug approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED)., Objective: This study aimed to identify potential safety signals of teprotumumab by analyzing postmarketing safety data from the FDA Adverse Event Reporting System (FAERS) database in 2023., Methods: The case/noncase approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant 95% CI for adverse events (AEs) that numbered 3 or more., Results: A total of 2158 cases were included in the analysis. Main safety signals identified were ear and labyrinth disorders, reproductive system and breast disorders, metabolism and nutrition disorders, and gastrointestinal disorders. Specifically, autophony (ROR [95% CI] = 4188.34 [1403.29-12500.8]), eyelid retraction (ROR [95% CI] = 2094.17 [850.69-5155.29]), permanent deafness (ROR [95% CI] = 1552.35 [789.07-3053.98]), bilateral deafness (ROR [95% CI] = 73.12 [41.14-129.97]), inflammatory bowel disease (ROR [95% CI] = 23.26 [13.46-40.19]), hyperglycemic hyperosmolar nonketotic syndrome (ROR [95% CI] = 17.75 [5.70-55.28]), and amenorrhea (ROR [95% CI] = 47.98 [36.22-63.54]) showed significant safety signals with teprotumumab., Conclusion: This study identified ear and labyrinth disorders, and reproductive system and breast disorders, as specific safety signals of teprotumumab. Clinicians and pharmacists should be vigilant regarding these AEs. However, available data are currently insufficient, and further pharmacovigilance and surveillance are needed to fully understand this issue., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Key Points: Utilization of orbital decompressions (ODS) increased (CAGR: +3.2%) from 2000 to 2019. FDA approved teprotumumab in January 2020; ODS utilization decreased (CAGR: -14.9%) from 2019 to 2022. In 2022, total spending was substantially higher for teprotumumab ($325 million) than surgery ($580,000)., (© 2024 ARS‐AAOA, LLC.)

Objective: Teprotumumab plays an important role in thyroid eye disease pathogenesis and progression. We intend to mine the adverse event (AE) signals from a relevant database, thereby contributing to the safe use of teprotumumab., Methods: The data obtained from the ASCII data packages in the FAERS database from January 2020 to the second quarter of 2023 were imported into the SAS software (version 9.4) for data cleaning and analysis. Disproportionality analysis was performed using the reporting odds ratio (ROR) in conjunction with the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) omnibus standard method to detect positive signals., Participants: This retrospective observational study relied on adverse drug reactions reported to the FDA through FAERS, which is a standard public system for spontaneous reporting., Results: Collectively, 2171 AE reports for teprotumumab were collected, among which 108 significant signals were identified involving 17 system organ classes. The SOC of ear and labyrinth disorders included the most AE signals and reports. Muscle spasms, fatigue, headache, nausea, diarrhea, alopecia, blood glucose increased, hypoacusis, tinnitus, and diabetes mellitus were the top ten PTs ranked by the frequency of reporting, meanwhile, the two high-strength signals of thyroid-stimulating immunoglobulin increase (ROR 662.89, 95% CI 182.40-2409.19) and gingival recession (ROR 125.13, 95% CI 79.70-196.45) were not documented in the drug instruction. Meanwhile, we found a higher risk of increased blood glucose, deafness, and decreased appetite for male patients, and headache for female patients., Conclusions: Clinical application of teprotumumab should be closely monitored for ototoxicity, nail abnormalities, and menstrual changes, as well as for AEs not mentioned in the drug instruction, including gingival recession, thyroid-stimulating immunoglobulin increase, and so on., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Teprotumumab was approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease in 2020. However, its adverse events (AEs) have not been investigated in real-world settings., Aim: This study aimed to detect and evaluate AEs associated with teprotumumab in the real-world setting by conducting a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database., Method: Reporting odds ratio (ROR) was used to detect risk signals from the data from January 2020 to March 2023 in the FAERS database., Results: A total of 3,707,269 cases were retrieved, of which 1542 were related to teprotumumab. The FAERS analysis identified 99 teprotumumab-related AE signals in 14 System Organ Classes (SOCs). The most frequent AEs were muscle spasms (n = 287), fatigue (n = 174), blood glucose increase (n = 121), alopecia (n = 120), nausea (n = 118), hyperacusis (n = 117), and headache (n = 117). The AEs with strongest signal strengths were autophony (ROR = 14,475.49), deafness permanent (ROR = 1853.35), gingival recession (ROR = 190.74), deafness neurosensory (ROR = 129.89), nail growth abnormal (ROR = 103.67), onychoclasis (ROR = 73.58), ear discomfort (ROR = 72.88), and deafness bilateral (ROR = 62.46). Eleven positive AE signals were found at the standardized MedDRA queries (SMQs) level, of which the top five SMQs were hyperglycemia/new-onset diabetes mellitus, hearing impairment, gastrointestinal nonspecific symptoms and therapeutic procedures, noninfectious diarrhea, and hypertension. Age significantly increased the risk of hearing impairment., Conclusion: This study identified potential new and unexpected AE signals of teprotumumab. Our findings emphasize the importance of pharmacovigilance analysis in the real world to identify and manage AEs effectively, ultimately improving patient safety during teprotumumab treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Teprotumumab (TPT) is a type I insulin-like growth factor receptor inhibitor, marketed as Tepezza; recently USFDA approved it for the treatment of thyroid eye disease (thyroid-associated ophthalmopathy (TAO), Graves ophthalmopathy/orbitopathy) in the USA. It is a monoclonal antibody although it was initially developed in collaboration with Genmab and Roche for the treatment of the tumour, but later it was investigated by River Vision Development Corporation and Horizon Therapeutics for its ophthalmic use. The drug has been designated as an orphan drug, breakthrough designation and fast-track designation. This review summarizes the milestones in the research and development including ongoing, clinical trial of TPT till now, foremost to this primary approval for thyroid-associated ophthalmopathy (TAO).