SynthesisDrugs2026
Efficacy and Safety of IGF-1 Receptor Inhibitors for Thyroid Eye Disease: Systematic Review and Meta-analysis of Randomized Controlled Trials.
Synthesis in Drugs, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
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Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
BACKGROUND AND
objectiveInsulin-like growth factor-1 receptor (IGF-1R) inhibitors represent the first and currently only US Food and Drug Administration (FDA)-approved disease-modifying therapy for thyroid eye disease (TED). Understanding their efficacy and safety is essential for treatment decision-making. A comprehensive analysis of randomized controlled trial (RCT) data of these drugs is necessary for defining reliably improved outcomes and commonly observed treatment-related adverse events. In this study, we aimed to evaluate the efficacy and safety profiles of IGF-1R inhibitors for treatment of TED as evidenced by RCTs.
methodsThis systematic review and meta-analysis was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251141789) and conducted according to Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines. PubMed, Embase, Web of Science, Cochrane Library, and EBSCO were searched through 10 December 2025. Eligible studies were RCTs comparing IGF-1R inhibitors with placebo in TED. Two reviewers independently performed study selection, data extraction, and quality assessment using the Cochrane risk of bias tool. Fixed- or random-effects models, selected according to the degree of statistical heterogeneity, were used to estimate pooled risk ratios (RRs) and mean differences (MDs), with subgroup, meta-regression, and sensitivity analyses exploring heterogeneity.
resultsA total of 669 patients participating in 7 RCTs were included from 957 articles screened. These include studies evaluating teprotumumab, IBI311, and veligrotug. Regarding primary outcomes, IGF-1R inhibitors improved proptosis significantly (RR = 7.71, 95% CI 5.04-11.79, P < 0.001) and increased overall response (RR = 8.74, 95% CI 5.61-13.62, P < 0.001). Secondary outcome analysis revealed a significant improvement with IGF-1R inhibitors versus placebo, including achieving clinical activity score (CAS) of 0 or 1 (RR = 3.19, 95% CI 2.40-4.24, P < 0.001), diplopia (RR = 1.95, 95% CI 1.52-2.50, P < 0.001), least squares mean (LSMean) change in proptosis (MD = - 2.22 mm, 95% CI - 2.45 to - 1.99 mm, P < 0.001) and LSMean change in quality of life (MD = 10.48, 95% CI 6.95-14.00, P < 0.001). Pooled adverse-event rate was higher in the active treatment group (RR = 1.15, 95% CI 1.06-1.24, P < 0.001). Subgroup analysis and meta-regression identified disease activity as a significant predictor of proptosis reduction, with greater efficacy in acute active TED, while an exploratory subgroup difference in diplopia response was observed between trials conducted in predominantly white and predominantly East Asian populations (P(Qint) = 0.027).
conclusionsIGF-1R inhibitors outperformed placebo across multiple efficacy outcomes. These findings confirm their robust efficacy in TED, particularly in active disease. Given the increased adverse event risk, IGF-1R inhibitors warrant vigilant monitoring, including baseline and on-treatment glycemic and audiometric assessments, to ensure optimal safety.
Identifiers
42782579What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.