Age, clinical activity may affect glucocorticoid therapy response for thyroid eye disease

Key takeaways:

• Older age and high clinical activity score lowered the odds for response to glucocorticoids in thyroid eye disease.
• More research is needed comparing glucocorticoids with teprotumumab and other treatments.

Older adults and those with a worse thyroid eye disease clinical activity score at baseline were less likely to respond to glucocorticoid therapy, according to findings published in Thyroid.

“The leading position of intravenous glucocorticoids as the first-line treatment for moderate to severe Graves’ orbitopathy in many countries worldwide, due to its availability and low cost, is being challenged by the new immunotherapies,” Maria-Cristina Burlacu, MD, deputy head of clinic in the department of endocrinology and nutrition at Cliniques Universitaires Saint-Luc, Université Catholique de Louvain in Belgium, told Healio. “Although the level of evidence, particularly with regard to long-term safety and sustainability of results, is still insufficient, the new immunotherapies could be a more effective and better-tolerated therapeutic alternative in selected cases.”

Burlacu and colleagues conducted a retrospective study of 64 adults with moderate to severe thyroid eye disease who were treated with IV glucocorticoids for 12 weeks according to European Group on Graves’ Orbitopathy (EUGOGO) protocol at a single center from 2003 to 2023. Patients were assessed at 6 months according to clinical judgment criteria as well as the EUGOGO 2021 revised composite index.

Glucocorticoid therapy began a median 4 months after thyroid eye disease diagnosis. The mean clinical activity score at baseline was 4.4 of a maximum 7 points, with 73% of participants having a clinical activity score of 4 or more points.

Factors tied to lower glucocorticoid response

According to clinical judgment, 75% of adults were deemed to be responsive to glucocorticoid therapy at 6 months. Those who responded to treatment were younger than nonresponders (mean age, 50.1 years vs. 56.6 years; P = .04) and responders had a lower mean baseline clinical activity score than nonresponders (4.2 vs. 5; P = .022). The responder group had a higher proportion of adults who never smoked vs. nonresponders (33% vs. 12.5%; P = .047).

In multivariable analysis using clinical judgment, older age (OR = 0.92; 95% CI, 0.86-0.99) and higher clinical activity score before glucocorticoid therapy (OR = 0.53; 95% CI, 0.31-0.9) were tied to a lower likelihood of responding to glucocorticoid treatment.

Maria-Cristina Burlacu

Among 44 adults who had enough data available to be evaluated through EUGOGO composite index, 73% were responsive to glucocorticoid therapy. Responders had a lower baseline clinical activity score as measured on a 5-point scale at 6 months than nonresponders (3.1 vs. 4.7; P < .001). There were no significant differences by age and smoking status when EUGOGO composite index was used.

In multivariable analysis using the EUGOGO composite index, older age (OR = 0.88; 95% CI, 0.77-0.99) and higher baseline clinical activity score (OR = 0.08; 95% CI, 0.01-0.38) were associated with lower odds for responding to glucocorticoid therapy.

Burlacu said it was surprising that there were no significant associations between glucocorticoid response and smoking or thyroid-stimulation hormone receptor antibody levels, two risk factors for thyroid eye disease onset and progression.

“This reflects the complexity of immune processes in the orbit and raises the question of the existence of other autoantigens involved in the pathogenesis of thyroid eye disease,” Burlacu said. “On the other hand, the variability in the individual predictive ability of different markers for treatment response pointed to the need for thyroid eye disease prediction models for treatment response resulting from the combination of clinical, biological and imaging markers.”

Individualizing care

When clinical judgment was used, the optimal cutoff tied to a poorer response to glucocorticoid therapy was a clinical activity score of 4.5 points or higher of a maximum of 7 points at baseline. When EUGOGO composite index was used, the optimal baseline clinical activity score cutoff was 3.5 points or higher of a possible 5 points.

Burlacu noted that the American Thyroid Association and the European Thyroid Association recommend teprotumumab-trbw (Tepezza, Amgen) for adults with active thyroid eye disease and significant proptosis. However, she added no randomized trials have been conducted comparing teprotumumab with glucocorticoids and other drugs and said such studies could better inform treatment recommendations and assist with individualizing therapy.

“As with many other diseases, we should take a personalized approach and choose the better treatment for our patients,” Burlacu said.

For more information:

Maria-Cristina Burlacu, MD, can be reached at maria.burlacu@saintluc.uclouvain.be.

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Sources/Disclosures

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Disclosures:
Burlacu reports being a member of the European Group on Graves’ Orbitopathy. Please see the study for all other authors’ relevant financial disclosures.

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