Keywords
Glucocorticoids
Teprotumumab
Tocilizumab
RAND/UCLA Appropriateness Method
How to Cite
Abstract
Background: Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves’ disease and a major cause of morbidity. Management of active, moderate-to-severe thyroid eye disease remains challenging due to clinical heterogeneity, a variable response to glucocorticoids, and an evolving evidence base for alternative therapies. Although international guidelines provide general recommendations, uncertainty persists regarding the role of biologics, immunosuppressants, and local interventions.
Objective: To assess the appropriateness and necessity of medical therapies for active, moderate-to-severe thyroid eye disease using the RAND/UCLA Appropriateness Method, integrating systematic evidence with expert consensus.
Methods: A systematic review of randomized trials, meta-analyses, systematic reviews, and observational studies was conducted following PRISMA standards. A multidisciplinary panel (n=10) rated 14 clinical scenarios across 238 intervention–scenario pairs in three rounds using a 9-point scale. Appropriateness was defined by median scores and the interpercentile range; necessity was evaluated for appropriate interventions according to RAND/UCLA criteria.
Results: Intravenous glucocorticoids were consistently rated as necessary as a first-line therapy. Teprotumumab and tocilizumab were considered appropriate in multiple scenarios, with teprotumumab frequently meeting necessity criteria. Mycophenolate was appropriate but not necessary, reflecting concerns about the robustness of the evidence and its modest efficacy. Rituximab was rated conservatively due to heterogeneous evidence and safety concerns, including dysthyroid optic neuropathy. Local therapies, such as periocular triamcinolone and botulinum toxin, were appropriate in several scenarios and necessary in selected cases.
Conclusions: Intravenous glucocorticoids remain the cornerstone of TED management. This consensus clarifies the role of emerging therapies and provides context-specific recommendations that complement existing guidelines.
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