Journal article
Teprotumumab for Thyroid-Associated Ophthalmopathy
The New England journal of medicine, Vol.376(18), pp.1748-1761
05/04/2017
DOI: 10.1056/NEJMoa1614949
PMCID: PMC5718164
PMID: 28467880
Abstract
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. 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. 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. 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 .).
Details
- Title: Subtitle
- Teprotumumab for Thyroid-Associated Ophthalmopathy
- Creators
- Terry J Smith - University of Michigan Medical SchoolGeorge J Kahaly - Johannes Gutenberg University MainzDaniel G Ezra - Moorfields Eye HospitalJames C Fleming - University of Tennessee Health Science CenterRoger A Dailey - Oregon Health and Science University HospitalRosa A TangGerald J Harris - Medical College of WisconsinAlessandro Antonelli - University of PisaMario Salvi - University of MilanRobert A Goldberg - University of California, Los AngelesJames W Gigantelli - University of Nebraska Medical CenterSteven M Couch - Washington University in St. LouisErin M Shriver - University of Iowa, Ophthalmology and Visual SciencesBrent R Hayek - Emory UniversityEric M Hink - University of Colorado DenverRichard M WoodwardKathleen GabrielGuido MagniRaymond S Douglas - University of Michigan Medical School
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.376(18), pp.1748-1761
- DOI
- 10.1056/NEJMoa1614949
- PMID
- 28467880
- PMCID
- PMC5718164
- NLM abbreviation
- N Engl J Med
- ISSN
- 1533-4406
- eISSN
- 1533-4406
- Publisher
- United States
- Grant note
- R01 EY008976 / NEI NIH HHS P30 EY007003 / NEI NIH HHS R01 EY021197 / NEI NIH HHS F31 EY007003 / NEI NIH HHS R01 DK063121 / NIDDK NIH HHS UM1 AI110557 / NIAID NIH HHS R01 FD004792 / FDA HHS R01 EY011708 / NEI NIH HHS
- Language
- English
- Date published
- 05/04/2017
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983980053102771
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