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Future clinical trials may be necessary to confirm if 1 treatment is superior to the other to a clinically relevant degree in patients with thyroid eye disease.
Research from a new meta-analysis suggest the use of intravenous methylprednisolone (IVMP) in patients with thyroid eye disease (TED) is associated with a small, not-clinically relevant change from baseline in proptosis versus placebo, with modest changes observed in diplopia.
Further data show that although the nonrandomized comparison suggested the use of teprotumumab, compared with IVMP, is associated with greater improvement in proptosis and higher reduction in diplopia, future randomized controlled trials would be warranted to determine if 1 treatment is clinically superior.
“Given the efficacy of teprotumumab and the limited efficacy of IVMP on proptosis and diplopia, it would be unethical to examine these outcomes in a placebo/IVMP trial,” wrote study author Raymond S. Douglas, MD, PhD, Cedars-Sinai Medical Center.
Data on teprotumumab or placebo were collected from 2 published trials and pooled to obtain treatment arms with 84 randomized patients in the teprotumumab arm and 87 randomized patients for placebo.
In the literature review, PubMed and Embase were searched for relevant RCTs and observational studies from database inception - October 2020 assessing the most commonly recommended dose of IVMP for those with moderate - severe active TED.
Study inclusion was based on patients with moderate - severe active TED receiving treatment with IVMP at a dosage of 4.5 g - 5 g over 12 weeks and reporting at least 1 of 2 outcomes of interest.
The change from baseline in proptosis and diplopia responses were evaluated by study investigators. They defined diplopia responses as a 1-grade or higher reduction in diplopia from baseline, with 1 as intermitten, 2 as incostant and 3 as constant using the Bahn-Gorman scale with the following grade.
The main outcomes for the study included changes in proptosis by millimeter and diplopia response (percentage with 1 grade reduction) from baseline to week 12 in patients receiving IVMP and placebo and to week 24 for those receiving teprotumumab.
A total of 1019 records were identified through the search and 6 were identified through manual searches, alerts, and secondary references. After exclusions including irrelevant dosage, time of assessment, or lack of reporting of relevant outcomes, 12 IVMP studies were included in the matching-adjusted indirect comparison.
For the proptosis and diplopia analysis, 419 and 125 patients receiving IVMP were included, respectively. The MAICs showed teprotumumab was associated with a statistically significantly greater change from baseline in proptosis, compared with IVMP (MD, -2.31 mm; 95% CI, -3.45 to -1.17 mm).
Then, the difference in proptosis change from baseline in the IVMP was -0.16 mm (95% CI, -1.55 to 1.22 mm) to week 12, versus placebo.
After adjustment for baseline characteristics, the results from MAICs showed that IVMP was associated with numerically increased odds of diplopia response compared with placebo (OR, 2.69; 95% CI, 0.94 - 7.70). Further, the teprotumumab diplopia response was greater compared to IVMP (odds ratio, 2.32; 95% CI, 1.07 - 5.03).
The study, “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,” was published in JAMA Ophthalmology.