Teprotumumab Shown to Have Favorable Safety Profile

Study suggests that teprotumumab may have fewer adverse outcomes than glucocorticoids when treating thyroid eye disease. Photo: Bobby Saenz, OD. Click image to enlarge. The insulin-like growth factor-1 receptor inhibitor teprotumumab has proven effective for thyroid eye disease (TED), but there is limited evidence on its long-term safety. In a recent study, researchers investigated the long-term cardiovascular, renal, infectious and safety outcomes of this newer therapeutic compared to intravenous (IV) glucocorticoids, oral glucocorticoids and conservative treatment in patients with TED. They found significantly lower risks of systemic complications and lower all-cause mortality rates. The findings were reported in Ophthalmology.Included were patients with TED who started teprotumumab, glucocorticoids or conservative treatment between January 2020 to December 2024 from 80 healthcare organizations in the United States. Outcomes included all-cause mortality and the risks of new-onset cardiovascular diseases, renal diseases, infectious outcomes and safety outcomes, including hearing loss, within five years after initiating treatment.Teprotumumab was associated with markedly lower all-cause mortality and reduced risks of acute myocardial infarction, cerebral infarction, peripheral vascular disease, heart failure, atrial fibrillation, acute kidney failure, emergency department visits, hospitalization, urinary tract infection, pneumonia and severe sepsis when compared to IV or oral glucocorticoids.There was no difference in the risks of diabetes, chronic kidney disease, inflammatory bowel disease or complications requiring a hearing device. All-cause mortality was also markedly reduced in teprotumumab users when compared to patients with conservative treatment. Previous studies have suggested that high levels of insulin-like growth factor receptor (IGF-1) are linked to a greater risk of morbidity and mortality, including diabetes and vascular diseases. “Therefore, it is biologically plausible that the inhibition of IGF-1R may prevent cardiorenal comorbidities in patients with TED who otherwise could develop these conditions when treated with glucocorticoids,” the authors wrote in their paper for Ophthalmology.This theory was supported by the current findings that the survival benefits and lower risks of infections following teprotumumab persisted when the treatment was compared to not only glucocorticoids but also conservative treatment, another active comparator that does not possess cardiotoxicities.“We are unsure of the significance of this finding, but our results may support the planning of studies on the cardiovascular and renal effects of teprotumumab and IGF-1R inhibition, in patients with and possibly without TED,” the authors explained in their paper.On the other hand, although patients receiving glucocorticoids demonstrated higher risks of adverse clinical outcomes compared to those receiving conservative treatment, patients on glucocorticoids were associated with a lower risk of death. The authors noted that the reasons for this finding are unclear, but it is possible that glucocorticoids may provide survival benefits by suppressing the inflammatory or autoimmunity processes of Graves’ disease, which is associated with increased mortality (TED is a common manifestation of the systemic autoimmune activity of Graves’ disease).It should be noted that there was an increased risk of hearing loss after starting teprotumumab compared to IV or oral glucocorticoids, but there was no difference in the need for hearing devices.The authors noted that most centers routinely perform audiometry during teprotumumab treatment, and this could result in an increased use of billing codes for hearing loss, when compared to patients not treated with teprotumumab. “Any patient who later received a diagnosis of hearing loss was also considered an outcome event in this study, despite some patients may only experience transient symptoms.”The authors suggest that further studies are warranted to validate the cardiovascular and renal benefits of teprotumumab and to determine whether these benefits persist in patients with pre-existing cardiorenal comorbidities but without TED.Click here for the journal source. Lo J-E, Freitag SK, Liu CY, et al. Long-term cardiovascular, renal and safety outcomes of teprotumumab versus systemic glucocorticoids in thyroid eye disease. Ophthalmology. May 13, 2025. [Epub ahead of print.]