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Meta-Analysis
. 2022 Apr 1;140(4):328-335.
doi: 10.1001/jamaophthalmol.2021.6284.

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

Raymond S Douglas  1 , Roger Dailey  2 , Prem S Subramanian  3 , Giuseppe Barbesino  4 , Shoaib Ugradar  5 , Ryan Batten  6 , Rana A Qadeer  7 , Chris Cameron  6
Affiliations
Meta-Analysis

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

Raymond S Douglas et al. JAMA Ophthalmol. .

Abstract

Importance: Thyroid eye disease can be a debilitating autoimmune disorder characterized by progressive proptosis or diplopia. Teprotumumab has been compared with placebo in randomized clinical trials, but not with intravenous methylprednisolone (IVMP), which sometimes is used in clinical practice for this condition.

Objective: To conduct a matching-adjusted indirect comparison of teprotumumab vs IVMP vs placebo.

Data sources: Deidentified patient-level data from teprotumumab trials and aggregate-level data from literature on the most recommended regimen of IVMP.

Study selection: PubMed and Embase were searched for randomized/observational studies using key terms and controlled vocabulary. Full texts of eligible articles were reviewed and cataloged.

Data extraction and synthesis: Conducted by 1 reviewer (R.A.Q.) and 1 verifier (R.B.), including study characteristics, eligibility criteria, baseline characteristics, and outcomes.

Main outcomes and measures: 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 in patients receiving teprotumumab.

Results: The search identified 1019 records, and 6 through manual searches, alerts, and secondary references. After excluding duplicates and screening full-text records, 12 IVMP studies were included in the matching-adjusted indirect comparison (11 for proptosis change [n = 419], 4 for diplopia response [n = 125], and 2 teprotumumab [n = 79] and placebo [n = 83] comparator studies). Treatment with IVMP resulted in a proptosis difference of -0.16 mm (95% CI, -1.55 to 1.22 mm) from baseline to week 12 vs placebo. The proptosis treatment difference between IVMP and teprotumumab of -2.31 mm (95% CI, -3.45 to -1.17 mm) favored teprotumumab. Treatment with IVMP (odds ratio, 2.69; 95% CI, 0.94-7.70) was not favored over placebo in odds of diplopia response; however, teprotumumab was favored over IVMP (odds ratio, 2.32; 95% CI, 1.07-5.03).

Conclusions and relevance: This meta-analysis suggests that use of IVMP is associated with a small, typically not clinically relevant, change from baseline in proptosis vs placebo, with modest changes in diplopia. While this nonrandomized comparison suggests that use of teprotumumab, compared with IVMP, is associated with greater improvements in proptosis and may be twice as likely to have a 1 grade or higher reduction in diplopia, randomized trials comparing these 2 treatments would be warranted to determine if 1 treatment is superior to the other to a clinically relevant degree.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Dailey reported grants and personal fees from Horizon Therapeutics during the conduct of the study and personal fees from Horizon Therapeutics outside the submitted work. Dr Subramanian reported grants and personal fees from GenSight Biologics, Horizon Therapeutics, and Viridian Therapeutics, as well as grants from Santhera Pharmaceuticals outside the submitted work. Dr Barbesino reported personal fees from Horizon outside the submitted work. Mr Batten reported funding from Horizon Therapeutics during the conduct of the study and funding from EVERSANA outside the submitted work. Mr Qadeer reported funding from Horizon Therapeutics during the conduct of the study and funding from EVERSANA outside the submitted work. Dr Cameron reported funding from Horizon during the conduct of the study, and funding from EVERSANA outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Meta-analyses to Obtain Pooled Estimates for Intravenous Methylprednisolone (IVMP) for Change From Baseline in Proptosis (A) and Diplopia Response (B)
Cfb indicates change from baseline; Cfbraw, raw change from baseline.
Figure 2.
Figure 2.. Unanchored Matching-Adjusted Indirect Comparisons (MAICs) and Pooled Results From Clinical Trials for Change From Baseline in Proptosis (A) and Diplopia Response (B)
Randomization controls for known/unknown confounders vs matching-adjusted indirect comparison controls for subset of known confounders. IVMP indicates intravenous methylprednisolone.
See this image and copyright information in PMC

Comment in

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