Immunomodulators in Graves' ophthalmopathy: a systematic review

Area of Science:

• Ophthalmology
• Endocrinology
• Rheumatology

Background:

• Graves' ophthalmopathy (GO), or thyroid eye disease, significantly impacts patient quality of life.
• Current management guidelines exist, but treatment approaches are evolving.
• Immunomodulatory drugs are being explored as novel therapeutic options for GO.

Purpose of the Study:

• To systematically review the efficacy of immunomodulatory drugs in treating Graves' ophthalmopathy.
• To evaluate newer targeted therapies, including biologics and disease-modifying antirheumatic drugs (DMARDs).

Main Methods:

• A comprehensive search of multiple databases (Cochrane, Embase, MEDLINE, etc.) was conducted up to October 10, 2025.
• Included studies focused on human patients with GO treated with targeted immunomodulatory therapies.
• The primary outcome was the Clinical Activity Score (CAS); a narrative synthesis and risk of bias assessment were performed.

Main Results:

• Teprotumumab and tocilizumab demonstrated benefits in reducing CAS and proptosis; rituximab results were inconclusive.
• Methotrexate and reduced-dose steroids improved CAS, while methotrexate and cyclosporine with steroids reduced proptosis.
• Adverse events were more frequent in patients treated with steroids compared to other immunomodulatory drugs.

Conclusions:

• Biologics and steroid-sparing agents may offer superior efficacy over steroids for reducing CAS in GO.
• The lack of head-to-head comparisons and study heterogeneity limit definitive conclusions.
• Further research is warranted to establish the comparative effectiveness of these emerging therapies.