Tocilizumab in Active, Moderate-to-Severe, Glucocorticoid-Resistant Thyroid Eye Disease: An Open-Label Prospective...

Treatment of active, moderate-to-severe thyroid eye disease (TED) remains a challenge. Up to 55% of patients show an incomplete response to intravenous (IV) glucocorticoids (GCs), and relapses are common. Tocilizumab (TCZ), a monoclonal antibody against the interleukin-6 receptor, has been proposed as a second-line therapy for GC-resistant TED.

We performed an open-label, prospective study at two tertiary TED referral centers (Warsaw, Poland; Belgrade, Serbia) from May 2022 to May 2025. Adults with active, moderate-to-severe, GC-resistant TED received TCZ 8 mg/kg IV every 4 weeks for four cycles and were followed for 24 weeks. Primary endpoints were (1) improvement in the composite ophthalmic score and (2) improvement in disease-specific quality of life (Graves' ophthalmopathy quality of life questionnaire [GO-QoL]). Secondary endpoints included changes in clinical activity score (CAS), proptosis, eyelid aperture, diplopia, thyrotropin receptor antibody (TRAb) levels, and safety. The trial was registered at ClinicalTrials.gov (NCT06367517).

A total of 44 patients underwent TCZ treatment (Warsaw, n = 32; Belgrade, n = 12). Both primary endpoints were met by 20/32 (62.5%) patients at Warsaw and all 12/12 (100%) patients at Belgrade. CAS reduction by ≥2 points was observed in 24/32 (75%) and 12/12 (100%) patients, respectively. A reduction of ≥2 mm in proptosis occurred in 19/32 (59.4%) and 7/12 (58.3%). Diplopia improved by ≥1 grade in Gorman score in 7/32 (21.9%) and 6/12 (50%). Eyelid aperture decreased by ≥2 mm in 11/32 (34.4%) and 8/12 (66.7%). Median TRAb levels decreased from 7.0 to 2.1 IU/L (Warsaw) and from 4.7 to 2.0 IU/L (Belgrade). No patients experienced TED deterioration. Adverse events occurred in 18/44 (40.9%) patients (47 events, only 1 severe).

In this prospective, real-world study conducted in two independent cohorts of patients with GC-resistant, active, moderate-to-severe TED, TCZ was associated with clinically meaningful improvements in composite ophthalmic score response, CAS, proptosis, and quality of life, with a generally acceptable safety profile. These findings support TCZ as an effective and safe second-line therapeutic option for GC-resistant TED.