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  • Teprotumumab may have greater efficacy than IVMP in thyroid eye disease

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    Review of: 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

    Douglas R, Dailey R, Subramanian P, et al. JAMA Ophthalmology, April 2022

    This study, a matching-adjusted indirect comparison (MAIC) of teprotumumab vs intravenous methylprednisolone (IVMP) vs placebo, assessed improvements in proptosis and diplopia with the most-recommended treatment regimen of IVMP and compared these results with teprotumumab and placebo in patients with moderate-to-severe thyroid eye disease (TED).

    Study design

    A systematic literature review identified 12 studies of IVMP (419 patients in total) and 2 clinical trials comparing teprotumumab vs placebo (84 patients randomized to teprotumumab and 87 patients randomized to placebo). The primary outcome of change from baseline in proptosis and diplopia was assessed at week 12 for IVMP and at week 24 for teprotumumab and placebo.

    Outcomes

    Unadjusted analyses found that IVMP treatment led to an overall proptosis reduction of 0.8 mm and a 50% diplopia response rate over 12 weeks. However, when the different groups were compared, proptosis reduction and diplopia response rates were better with teprotumumab than with IVMP, and both treatments had more favorable outcomes than placebo.

    Limitations

    This meta-analysis attempts to compare results between different studies by matching patients to the best of the authors’ abilities. Because TED is a heterogeneous disease, a meta-analysis can be extremely challenging, and results should be viewed with caution. As noted in the accompanying editorial to the article, this type of study (MAIC) “can be biased by unobserved cross-trial differences. In addition, it is not always possible to match outcome definitions and inclusion/exclusion criteria perfectly.”

    Clinical significance

    The use of teprotumumab has demonstrated significant improvement in proptosis and diplopia compared with placebo in the treatment of active moderate-to-severe TED. This study attempts to compare the effectiveness of teprotumumab vs. the gold-standard treatment of IVMP through a meta-analysis. The results suggest that teprotumumab is superior to IVMP with regard to proptosis and diplopia reduction. As the cost differential between these two treatments is considerable, it is time to call for a prospective, randomized, case-controlled study directly comparing teprotumumab to IVMP.