Both proptosis and the Clinical Activity Score were reduced with teprotumumab, an insulin-like growth factor I receptor inhibitor, when compared with placebo in patients with active ophthalmopathy, according to findings published in the New England Journal of Medicine.
The multicenter double-masked randomized placebo-controlled trial (Teprotumumab Treatment in Patients With Active Thyroid Eye Disease; ClinicalTrials.gov identifier: NCT01868997) included 88 patients with active ophthalmopathy who had been diagnosed ≤9 months after symptom onset. The intention-to-treat population (n=87) had received >1 infusion.
Terry J. Smith, MD, of the Kellogg Eye Center and University of Michigan Medical School, Ann Arbor, and fellow researchers randomly assigned patients to receive either placebo (n=45) or teprotumumab (n=42) administered intravenously once every 3 weeks for a total of 8 infusions.
Response in the study eye — defined as a reduction of ≥2 points in the Clinical Activity Score (with a score of ≥3 signifying active thyroid-associated ophthalmopathy) and a reduction of ≥2 mm in proptosis at week 24 — served as the primary end point. Proptosis, the Clinical Activity Score, and results on the Graves’ ophthalmopathy-specific quality-of-life questionnaire served as secondary end points.
Intention-to-treat results indicated that patients given teprotumumab were more likely to experience a response at 24 weeks than patients given placebo (69% vs 20%; P <.001).
The researchers observed that the therapeutic effects of the study drug were rapid. Specifically, at 6 weeks, 43% of patients in the teprotumumab arm experienced a response compared with 4% in the placebo arm (P <.001).
Hyperglycemia in patients with diabetes was the only drug-related adverse event, which was well controlled by adjustment of diabetes medication.
A study limitation of note, according to the researchers, was that only patients with active disease of recent onset, with a Clinical Activity Score ≥4, were enrolled. “Thus, the potential of teprotumumab in benefiting patients with milder, less active, or stable disease was not assessed,” the researchers wrote.
Another limitation is that orbital imaging was not performed, so it remains unknown if teprotumumab therapy had an impact on orbital tissues.
Despite the study’s limitations, the researchers concluded that by reducing proptosis and the Clinical Activity Score, as well as improving quality of life, teprotumumab provided clinical benefits for patients with active, moderate to severe thyroid-associated ophthalmopathy.
A full list of author disclosures can be viewed here.
Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376:1748-1761. doi:10.1056/nejmoa1614949