Phase 2/3 results show teprotumumab effective treatment option for TED

Reviewed by George J. Kahaly, MD, PhD

Pooled data from the phase 2 and 3 clinical trials of teprotumumab-trbw, (Tepezza; Horizon Therapeutics) showed that the drug significantly improved the clinical course of active thyroid eye disease (TED) over the long term in many patients and even in those with more severe baseline disease.

TED is characterized by inflammation and proptosis and diplopia refractory to treatment.

Related: Study: Therapy reduces proptosis, diplopia in TED

Teprotumumab, which seems to be an important therapeutic advancement for this patient population, is an insulinlike growth factor 1 receptor–inhibiting monoclonal antibody that received FDA approval in January 2020, based on 2 double-masked, placebo-controlled, multicenter, randomized trials carried out in the United States and Europe.

George J. Kahaly, MD, PhD, and colleagues took their investigation a step further in the current pooled analysis, focusing on proptosis and diplopia by evaluating the short- and long-term aggregate response to teprotumumab from the pair of phase 2 and phase 3 trials.

He is a professor of medicine and endocrinology/metabolism, Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany.

In those 24-week studies, the patients received either active treatment or placebo once every 3 weeks, for a total of 8 infusions.

Patients were evaluated at 7, 24, and 51 weeks after the last infusion of teprotumumab.

Related: Advancement in TED treatment is a bright spot

The investigators calculated the composite outcome of the data from the 2 trials as the proportions of patients with improvement in 1 eye in at least 2 of these parameters: proptosis, diplopia, eyelid swelling, lid aperture, global motility, and the Clinical Activity Score (CAS) without decreases in at least 2 of these in either eye.

Eighty-four patients were randomly assigned to teprotumumab and 87 to placebo.

At the 24-week evaluation, the authors reported that more patients randomly assigned to teprotumumab achieved a minimal 2-mm decrease in proptosis compared with placebo—77% vs 15%, respectively, a difference that achieved significance (P < .0001).

The number of diplopia responders was also significantly higher with teprotumumab than placebo at week 24—70% vs 18%, respectively, except among tobacco users and those with a low thyrotropin binding inhibiting immunoglobulin serum concentration.

Large improvements in quality of life also were seen. The beneficial results also withstood the test of time.

Related: Thyroid eye disease: Not limited to visual impairment

Seven weeks after the last dose of teprotumumab, the following responses were seen: proptosis (87%), diplopia (66%), and the composite ophthalmic response (92%).

There was no evidence of acute TED rebound 7 weeks after the last drug infusion.

No new safety concerns were found during follow-up or in the pooled analysis compared with the safety evaluation in the 24-week studies.

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George J. Kahaly, MD, PhD
e:george.kahaly@unimedizin-mainz.de
This study was funded by Horizon Therapeutics.

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Reference

1. Kahaly GJ, Douglas RS, Holt RJ, Sile S, Smith TJ. Teprotumumab for patients with active thyroid eye disease: a pooled data analysis, subgroup analyses, and off-treatment follow-up results from two randomised, double-masked, placebo-controlled, multicentre trials. Lancet Diabetes Endocrinol. 2021;9(6):360-372. doi:10.1016/S2213-8587(21)00056-5