Factors Associated with Response to Intravenous Glucocorticoids in Active Moderate-to-Severe Thyroid Eye Disease

Background: Intravenous glucocorticoids (IVGCs) are the first-line treatment for active moderate-to-severe thyroid eye disease (TED) in many countries worldwide, mainly because of their anti-inflammatory efficacy. Methods: Retrospective cohort study of 64 patients with active moderate-to-severe TED, without dysthyroid optic neuropathy, treated between 2003 and 2023 at a single tertiary centre with the 12 weeks IVGC EUGOGO (European Group on Graves Orbitopathy) protocol. All patients were evaluated for response to IVGC according to the clinical judgment (CL) and 44/64 (69%) patients were also evaluated with the EUGOGO 2021 revised composite index (CI). Results: The mean patients' age at IVGC initiation was 51.7 ± 11 years, 47/64 (73.5%) were women, 56/64 (87.5%) were Caucasians, and 33/64 (51.5%) were active smokers. At 6 months after IVGC, 48 out of 64 (75%) patients evaluated with CL and 32 out of 44 (73%) patients evaluated with EUGOGO CI responded to the treatment. Nonresponders tended to be older than responders (56.6 ± 10.2 vs. 50.1 ± 10.8 years, p = 0.040 for CL and 56.5 ± 11.9 vs. 50.3 ± 11.6 years, p = 0.131 for EUGOGO CI) and had higher clinical activity score (CAS) before IVGC (5.0 ± 1.1 vs.4.2 ± 1.1, p = 0.022 for CL and 4.7 ± 0.6 vs. 3.1 ± 0.8, p < 0.001 for EUGOGO CI). In patients evaluated with CL or EUGOGO CI, respectively, multivariable logistic regression identified age at IVGC initiation (odds ratio [OR] = 0.92 [95% confidence interval (CI) 0.86-0.99], p = 0.024 and OR = 0.88 [CI 0.77-0.99], p = 0.046) and CAS before IVGC (OR = 0.53 [CI 0.31-0.90], p = 0.021 and OR= 0.08 [CI 0.01-0.38], p = 0.001) but not active smoking as independent factors associated with response to IVGC. The optimal cut-off associated with poorer response to IVGC was CAS ≥4.5/7 (66.7% specificity, 56.3% sensitivity; Area Under the Curve [AUC] = 0.689 [CI 0.54-0.83], p = 0.010) in patients evaluated with CL and CAS ≥3.5/5 (65.6% specificity, 91.7% sensitivity; AUC = 0.910 [CI 0.80-1.01], p < 0.001) in patients evaluated with EUGOGO CI. Conclusion: Older age and higher CAS before treatment were associated with poorer response to IVGC. Patients with these characteristics could be offered other immunotherapies as a first-line treatment for active moderate-to-severe TED.