Endocrine Abstracts

Introduction: Treatment of Graves’ Orbitopathy (GO) remains a challenge. Approximately 20-30% of patients show resistance or incomplete response to high-dose glucocorticoid therapy. According to current guidelines the use of tocilizumab (TCZ), a monoclonal antibody against IL6 receptor, has been proposed as one of the second-line therapies.

Objectives: Our aim was to assess the efficacy and safety of TCZ treatment in patients with glucocorticoid-resistant GO.

Methods: We are currently conducting a prospective, observational, single-center study of glucocorticoid-resistant GO treated with TCZ. This report aims to present the effects of TCZ therapy of the first 19 enrolled patients from 2021-2024. TCZ was administrated at a dose of 8 mg/kg, given once every four weeks (4 cycles). The primary outcomes were disease improvement assessed by the modified EUGOGO composite ophthalmic score, and improvement of quality of life. Response to treatment was considered positive in case of improvement of at least 2 of the following features in 1 eye, without concomitant deterioration in the other eye: a. decrease in eyelid aperture by at least 2 mm, b. decrease in exophthalmos by at least 2 mm, c. increase in eye motility by at least 8°, d. decrease in 7-item clinical activity score (CAS) by at least 2 points. The secondary outcomes were: achievement of disease inactivation, improvement in soft tissue signs and symptoms, proptosis and adverse effects.

Results: Nineteen patients (38 eyes) with active glucocorticoid-resistant GO (13 females, median age 49 years, median duration of GO 12 months) were included. The follow-up period after first dose was 16 weeks. We observed improvement in composite ophthalmic score in 11 out of 19 patients. In 12/19 and 11/19 patients we noted ≥6 points improvement in GO-QOL subscales for visual functioning and appearance, respectively. Diplopia improved (Gorman scale) in 2 out of 14 patients. The improvement in seven-item CAS by ≥2 points was reported in 15 out of 19 patients (disease inactivation CAS≤1 in 6/19 patients). Moreover, analyzing individual eyes we observed: the reduction of proptosis by at least 2 mm in 15/32 eyes, the reduction of palpebral aperture by at least 2 mm in 15/38 eyes; the reduction of lagophthalmos by at least 2 mm in 4/9 eyes. Adverse events during TCZ treatment were mild and minor. Progression of GO during treatment did not occur.

Conclusion: Our results further support TCZ as an effective and safe therapeutic option for patients with glucocorticoid-resistant GO.

Key words: Graves’ disease; thyroid orbitopathy; second-line treatment; tocilizumab; glucocorticoid-resistant orbitopathy