Teprotumumab Offers Stronger Proptosis, Diplopia Management for TED Patients Than Intravenous Methylprednisolone

Macro closeup of young woman face portrait in profile side with Grave's disease hyperthyroidism symptoms of ophthalmopathy bulging eyes proptosis edema
Macro closeup of young woman face portrait in profile side with Grave’s disease hyperthyroidism symptoms of ophthalmopathy bulging eyes proptosis edema
The difference between IVMP and a placebo were not clinically relevant, according to the investigation.

Teprotumumab may be a more effective treatment for proptosis and diplopia associated with thyroid eye disease (TED) than intravenous methylprednisolone (IVMP), according to a systematic review and meta-analysis published in JAMA Ophthalmology. However, the study emphasizes that a head-to-head trial is necessary to establish its superiority.

The investigators searched publication databases through April 2021 for studies of IVMP or teprotumumab for the treatment of proptosis or diplopia among patients with TED. The 12 included studies assessed proptosis (n=419) and diplopia (n=125) outcomes.

The patient populations were between the ages of 35 and 52 years, women comprised 35% to 80%, TED had onset less than 1 year previously, and 22% to 76% of patients smoked.

Patients who used teprotumumab experienced better improvements to their proptosis compared with those who used IVMP (MD -2.31, 95% CI, -3.45 to -1.17 mm) and those who used a placebo (MD -2.80, 95% CI, -3.28 to -2.32). IVMP was not associated with proptosis improvement compared with placebo (MD -0.16, 95% CI, -1.55 to 1.22 mm).

For diplopia, IVMP was associated with increased odds of response compared with placebo (OR 2.69, 95% CI, 0.94-7.70) and teprotumumab increased odds compared with IVMP (OR 2.32, 95% CI, 1.07-5.03) or placebo (OR 5.41, 95% CI, 2.45-11.97).

This study was limited by the fact that the studies did not have a common comparator arm. The results of this indirect comparison should be confirmed in a head-to-head trial.

“IVMP is associated with a small, typically not clinically relevant, change from baseline in proptosis vs placebo, with modest changes in diplopia” researchers report. “While this nonrandomized comparison suggests that teprotumumab, as compared with IVMP, is associated with greater improvements in proptosis and may be twice as likely as to have a 1 grade or higher reduction in diplopia, randomized controlled trials comparing these two treatments would be warranted to determine if one treatment is superior to the other to a clinically relevant degree.”

Disclosure: Multiple study authors declared affiliations with the biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Douglas RS, Dailey R, Subramanian PS, et al. Proptosis and diplopia response with teprotumumab and placebo vs the recommended treatment regimen with intravenous methylprednisolone in moderate to severe thyroid eye disease: a meta-analysis and matching-adjusted indirect comparison. JAMA Ophthalmol. Published online February 17, 2022. doi:10.1001/jamaophthalmol.2021.6284