Teprotumumab for Thyroid-Associated Ophthalmopathy

BACKGROUND: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves' ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed. RESULTS: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. CONCLUSIONS: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997 .)

The American College of Surgeons Responds to COVID-19

© 2020 The COVID-19 pandemic abruptly, and perhaps irrevocably, changed the way we live, conduct our business affairs, and practice medicine and surgery. In mid-March 2020, as COVID-19 infections escalated exponentially across many areas of the US, the Centers for Disease Control (CDC), the Surgeon General, and the American College of Surgeons (ACS) recommended that hospitals and surgeons postpone non-urgent operations in order to provide care to COVID-19 patients.1-3 It quickly became obvious that the COVID-19 pandemic presented unprecedented medical challenges. ACS leadership, including the Board of Regents and Officers (Appendix), worked with the ACS Executive Director (Dr David Hoyt) and staff to rapidly organize a response to the COVID-19 crisis. The aim of this effort was to support ACS members and Fellows, as well as the broader medical community, in continuing to provide optimal patient care. Because other similar public health crises could arise in the future, we report the measures taken by the ACS to respond to the COVID-19 pandemic