Pharmacologic Therapies for Active Moderate-to-Severe TED: A Comprehensive Systematic Review

Area of Science:

• Ophthalmology
• Endocrinology
• Immunology

Background:

• Moderate-to-severe thyroid eye disease (TED) is an inflammatory condition impacting vision.
• Current mainstay treatment involves intravenous glucocorticoids.
• Biologic and immunosuppressive agents are emerging alternatives for steroid-refractory cases.

Purpose of the Study:

• To compare the efficacy and safety of medical treatments for active moderate-to-severe TED.
• To determine the optimal therapeutic positioning of various pharmacological interventions.
• To provide an evidence-based framework for clinical decision-making.

Main Methods:

• Comprehensive literature search of PubMed, Embase, and Cochrane Library through February 2025.
• Inclusion of randomized controlled trials, meta-analyses, systematic reviews, and observational studies.
• Evaluation of outcomes including proptosis reduction, Clinical Activity Score (CAS), diplopia, and safety.

Main Results:

• Intravenous glucocorticoids (IVGCs) showed consistent efficacy in controlling inflammation with good tolerability.
• Teprotumumab demonstrated the highest efficacy across domains but faced safety and access limitations.
• Rituximab, tocilizumab, and mycophenolate mofetil showed moderate efficacy, especially in refractory cases.

Conclusions:

• IVGCs remain the most consistently supported first-line therapy for moderate-to-severe TED.
• IGF-1R-targeted biologic therapy offers comprehensive efficacy for selected patients.
• This review aids therapeutic decision-making in managing active TED.