Neuro-Ophthalmic Literature Review

Abstract

Neuro-Ophthalmic Literature Review David A. Bellows, Noel C.Y. Chan, John J. Chen, Hui-Chen Cheng, Peter W. MacIntosh, Jenny A. Nij Bijvank, Panitha Jindahra, and Michael S. Vaphiades Finally, a targeted treatment for active thyroid eye disease! Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382(4): 341–352. doi:10.1056/NEJMoa1910434. Teprotumumab is an insulin-like growth factor I receptor (IGF-IR) inhibitor recently approved by the FDA for treatment of thyroid eye disease. In this phase 3 multicentre trial 41 patients with active thyroid eye disease were assigned to receive teprotumumab or placebo once every three weeks for 21 weeks. The primary outcome was a ≥ 2 mm reduction in proptosis at week 24. Secondary outcomes included; the overall response (defined as a ≥ 2 reduction in the Clinical Activity Score plus a ≥ 2 reduction in proptosis), a Clinical Activity Score of 0 or 1, the mean change in proptosis during the trial, a diplopia response and, finally, the mean change in overall score on quality of life measures. With respect to the primary outcome, 83% of patients receiving teprotumumab showed a ≥ 2 mm reduction in proptosis as compared to 10% of those receiving placebo. This response was seen early, at week six, in most patients, and increased throughout the trial. At week 24 the mean reduction in proptosis in the teprotumumab group was 3.32 mm. All secondary outcomes were also significantly better in the teprotumumab group. Orbital imaging was obtained in six patients in the teprotumumab group which showed a 35% reduction in mean extraocular muscle volume. Orbital fat volume was decreased by 40% or more in two patients. Most adverse events were of grade 1 or 2 and occurred in at least 5% of patients who received teprotumumab. Two patients suffered infusion reactions. One of these patients discontinued the trial. The second patient was able to remain in the study. This patient was premedicated and treated with a slower rate of infusion. Other adverse effects in the group receiving teprotumumab included two patients with mild hyperglycaemia and five patients who suffered hearing impairment which resolved in all cases and five patients had weight loss (one was intentional). Two patients suffered serious reactions which included pneumothorax and an infusion reaction.