Teprotumumab Proves Benefit in Longer Duration Thyroid Eye Disease

Terry Smith, MD

New research related to teprotumumab (Tepezza) is providing insight into the effects of the agent in thyroid eye disease according to disease duration and need for retreatment.

Presented at the 90th Annual Meeting of the American Thyroid Association (ATA), results of the study, which assessed data from OPTIC and OPTIC-X trials, suggest responders to initial therapy maintained benefit during long-term follow-up and also suggest those with an insufficient initial response or who flare may benefit from additional teprotumumab therapy.

“Findings from this extended follow-up period reinforce previously-reported data showing that the majority of people treated with TEPEZZA have a sustained response,” said senior investigator Terry J. Smith, MD, Michigan Medicine Eye Plastic, Facial Cosmetic & Orbital Surgery, Kellogg Eye Center, University of Michigan Medical School. “This is the longest period of follow-up data we have for TEPEZZA and it can play an important role in helping physicians determine when in the disease course to optimally prescribe the medicine for their patients.”

With approval from the US FDA in early 2020, teprotumumab offered many patients the first hope at relief from proptosis in TED. Backed by results of the OPTIC trial and unanimous support from the FDA Dermatologic and Ophthalmic Drugs Advisory Committee, the IGF-1R inhibitor became the first therapy indicated for TED with approval in January 2020. Since approval, multiple studies have come out examining the effects of teprotumumab, including effects of diabetes on disease progression in TED and the potential risk of hearing loss and tinnitus observed with use of the medication. The current study, which was sponsored by Horizon Therapeutics, was designed to assess the long-term effects of teprotumumab in patients from the OPTIC trial who completed the 72-week follow-up, non-responders, or those who flared during follow-up, and non-flare patients within OPTIC-X.

Results of the investigators' analyses suggested 90% (n=18) of the OPTIC responders completing 72 weeks of follow-up received no additional therapy as of week 120. Of those who did, 1 patient received teprotumumab after approval and 1 underwent eyelid surgery 1 year after last dose. Of note, the patient receiving teprotumumab following approval received teprotumumab 16 months after the final OPTIC dose. Of the 37 placebo-treated OPTIC patients, 89.2% (n=33) became proptosis responders with teprotumumab treatment in OPTIC-X, which investigators noted was equivalent to the response rate observed in OTPIC despite having a longer disease duration.

Further analysis indicated proptosis, overall, CAS 0/1 and diplopia responses were maintained in 90.6%, 91.7%, 95.2%, and 85.7% of patients, respectively, at week 48. When assessing a cohort of 5 non-responders from the OPTIC study who were retreated in OPTIC-X, 2 experienced response, 1 had a proptosis reduction of 1.5 mm, and 2 discontinued early. Among the responders who flared during follow-up, 62.5% responded when retreated with a mean proptosis reduction of 1.9 (SD, 1.2) mm from OPTIX-X baseline and a mean reduction of 3.3 (SD, 0.7) mm from OPTIOC baseline.

Among a cohort of 47 patients who completed the OPTIC-X trial, the median overall GO-QOL score was 88. Additionally, among those treated for the first time, the mean change from baseline was 17.5 (SD, 17.5) and 16.7 (SD, 20.3) in visual function and appearance scales, respectively.

This study, “Teprotumumab for Thyroid Eye Disease (TED): Efficacy in Longer Duration Disease, Retreatment and Long-Term Follow-up,” was presented at ATA 2021.