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DOI: 10.1055/a-2737-3576
Assessing the Role of Tocilizumab in the Treatment of Thyroid Eye Disease: A Retrospective Single Centre Analysis
Article in several languages: English | deutschAuthors
Abstract
Background Due to the variable course of thyroid eye disease (TED), treatment should be tailored to disease severity, individual risk factors, and clinical course. This study is based on a retrospective analysis at the orbital centre of the University Eye Clinic Essen and evaluates the efficacy of the IL-6 receptor blocker tocilizumab as a second-line therapy in patients with therapy-refractory TED.
Patients/Methods After approval of cost coverage, 20 patients were treated with tocilizumab over a mean period of 4.8 ± 2.7 months. The following parameters were assessed: sex, age, underlying thyroid disease, disease activity and severity, prior therapies, visual acuity, intraocular pressure, eyelid position, exophthalmos, monocular excursions, strabismus/diplopia, levels of TSH receptor antibodies (TRAb), and adverse events.
Results The female-to-male ratio was 3 : 1. Mean patient age was 58.2 ± 8.5 years. The majority (90%, n = 18) had Gravesʼ disease; one patient had primary hypothyroidism and one was euthyroid. All patients had previously failed various treatment regimens (median cumulative steroid dose 4.6 g [1.5 – 7.5 g], 55% mycophenolate, 65% orbital apex radiation, 20% balanced orbital decompression). Among 17 patients with detectable TRAb at baseline, mean antibody levels decreased by 48.4%. A reduction of at least 30% was achieved in 70.6% of these patients (n = 17). A decrease in the Clinical Activity Score (CAS) by ≥ 2 points was observed in 70% of cases. The mean inflammation score (maximum 20 points per patient) decreased from 8.8 ± 3.9 to 3.4 ± 2.4. The effect on exophthalmos was moderate: mean reduction was 0.9 ± 1.8 mm (range − 6 mm to + 3 mm). A decrease of ≥ 2 mm was documented in 25% of patients, whereas an increase was noted in 12.5% (0.5 to 3 mm). Improvement in ocular motility was documented in 22.5% of patients, while 10% showed deterioration.
Discussion This cohort exclusively included therapy-refractory patients, some with protracted disease. The significant reduction in inflammation and particularly in TRAb levels, as a biomarker of disease activity, demonstrate the efficacy of tocilizumab in this highly selected population. Tocilizumab may therefore be an important treatment option for patients with high antibody levels and predominantly inflammatory disease manifestations. Further studies are warranted to evaluate whether it reduces the risk of relapse after successful treatment with an IGF-1 receptor blocker.
Publication History
Received: 15 July 2025
Accepted: 28 October 2025
Accepted Manuscript online:
03 November 2025
Article published online:
12 December 2025
© 2025. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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References/Literatur
- 1 Davies TF, Andersen S, Latif R. et al. Gravesʼ disease. Nat Rev Dis Primers 2020; 6: 52
- 2 Chin YH, Ng CH, Lee MH. et al. Prevalence of thyroid eye disease in Gravesʼ disease: A meta-analysis and systematic review. Clin Endocrinol (Oxf) 2020; 93: 363-374
- 3 Lee ACH, Kahaly GJ. Pathophysiology of thyroid-associated orbitopathy. Best Pract Res Clin Endocrinol Metab 2023; 37: 101620
- 4 Plöhn S, Edelmann B, Japtok L. et al. CD40 Enhances Sphingolipids in Orbital Fibroblasts: Potential Role of Sphingosine-1-Phosphate in Inflammatory T-Cell Migration in Gravesʼ Orbitopathy. Invest Ophthalmol Vis Sci 2018; 59: 5391-5397
- 5 Wiersinga WM, Eckstein AK, Žarković M. Thyroid eye disease (Gravesʼ orbitopathy): clinical presentation, epidemiology, pathogenesis, and management. Lancet Diabetes Endocrinol 2025; 13: 600-614
- 6 Pérez-Moreiras JV, Varela-Agra M, Prada-Sánchez MC. et al. Steroid-Resistant Gravesʼ Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience. J Clin Med 2021; 10: 706
- 7 Salvi M, Vannucchi G, Currò N. et al. Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe Gravesʼ orbitopathy: a randomized controlled study. J Clin Endocrinol Metab 2015; 100: 422-431
- 8 Cheetham TD, Cole M, Abinun M. et al. Adjuvant Rituximab-Exploratory Trial in Young People With Graves Disease. J Clin Endocrinol Metab 2022; 107: 743-754
- 9 Bartalena L, Kahaly GJ, Baldeschi L. et al. The 2021 European Group on Gravesʼ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Gravesʼ orbitopathy. Eur J Endocrinol 2021; 185: G43-G67
- 10 Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol 2015; 16: 448-457
- 11 Murdock J, Nguyen J, Hurtgen BJ. et al. The role of IL-6 in thyroid eye disease: an update on emerging treatments. Front Ophthalmol (Lausanne) 2025; 5: 1544436
- 12 Pérez-Moreiras JV, Alvarez-López A, Gómez EC. Treatment of active corticosteroid-resistant Gravesʼ orbitopathy. Ophthalmic Plast Reconstr Surg 2014; 30: 162-167
- 13 Sanchez-Bilbao L, Martinez-Lopez D, Revenga M. et al. Anti-IL-6 Receptor Tocilizumab in Refractory Gravesʼ Orbitopathy: National Multicenter Observational Study of 48 Patients. J Clin Med 2020; 9: 2816
- 14 Perez-Moreiras JV, Gomez-Reino JJ, Maneiro JR. et al. Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Graves Orbitopathy: A Randomized Clinical Trial. Am J Ophthalmol 2018; 195: 181-190
- 15 Habroosh FA, Albrashdi SS, Alsaadi AH. et al. Tocilizumab use for optic nerve compression in thyroid eye disease: a prospective longitudinal cohort. Int Ophthalmol 2024; 44: 222
- 16 Lee C, Park JW, Kim YD. et al. Efficacy of tocilizumab in patients with moderate-to-severe corticosteroid-resistant thyroid eye disease: a prospective study. Int Ophthalmol 2024; 44: 179
- 17 Alves Junior JM, Bernardo W, Villagelin D. Effectiveness of Different Treatment Modalities in Initial and Chronic Phases of Thyroid Eye Disease: A Systematic Review With Meta-analysis. J Clin Endocrinol Metab 2024; 109: 2997-3009
- 18 Duarte AF, Xavier NF, Sales Sanz M. et al. Efficiency and Safety of Tocilizumab for the Treatment of Thyroid Eye Disease: A Systematic Review. Ophthalmic Plast Reconstr Surg 2024; 40: 367-373
- 19 European Group on Graves Orbitopathy (EUGOGO), Wiersinga WM, Perros P, Kahaly GJ et al.. Clinical assessment of patients with Gravesʼ orbitopathy: the European Group on Gravesʼ Orbitopathy recommendations to generalists, specialists and clinical researchers. Eur J Endocrinol 2006; 155: 387-389
- 20 Mourits MP, Koornneef L, Wiersinga WM. et al. Clinical criteria for the assessment of disease activity in Gravesʼ ophthalmopathy: a novel approach. Br J Ophthalmol 1989; 73: 639-644
- 21 Eckstein AK, Plicht M, Lax H. et al. Clinical results of anti-inflammatory therapy in Gravesʼ ophthalmopathy and association with thyroidal autoantibodies. Clin Endocrinol (Oxf) 2004; 61: 612-618
- 22 Bartalena L, Kahaly GJ, Baldeschi L. et al. The 2021 European Group on Gravesʼ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Gravesʼ orbitopathy. Eur J Endocrinol 2021; 185: G43
- 23 Perez-Moreiras JV, Gomez-Reino JJ, Maneiro JR. et al. Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Graves Orbitopathy: A Randomized Clinical Trial. Am J Ophthalmol 2018; 195: 181-190
- 24 Boutzios G, Chatzi S, Goules AV. et al. Tocilizumab improves clinical outcome in patients with active corticosteroid-resistant moderate-to-severe Gravesʼ orbitopathy: an observational study. Front Endocrinol (Lausanne) 2023; 14: 1186105
- 25 Dorado Cortez O, Grivet D, Perrillat N. et al. Treatment of corticosteroid-resistant Gravesʼ orbitopathy with tocilizumab: a single-centre prospective study. Orbit 2023; 42: 411-417
- 26 Moi L, Hamedani M, Ribi C. Long-term outcomes in corticosteroid-refractory Gravesʼ orbitopathy treated with tocilizumab. Clin Endocrinol (Oxf) 2022; 97: 363-370
- 27 Pampín-Sánchez R, Martínez-Mugica-Barbosa C, Fonseca-Aizpuru EM. et al. Outcome of tocilizumab treatment in corticosteroid-resistant thyroid eye disease. Med Clin (Barc) 2023; 160: 113-117
- 28 Sánchez-Bilbao L, Martínez-López D, Revenga M. et al. Anti-IL-6 Receptor Tocilizumab in Refractory Gravesʼ Orbitopathy: National Multicenter Observational Study of 48 Patients. J Clin Med 2020; 9: 2816
- 29 Lin S, Ou X, Cai L. et al. Efficacy and safety of Tocilizumab for thyroid eye disease: a systemic review and Meta-analysis. J Endocrinol Invest 2025; 48: 1951-1965
- 30 Douglas RS, Couch S, Wester ST. et al. Efficacy and Safety of Teprotumumab in Thyroid Eye Disease Patients with Long Duration and Low Disease Activity. J Clin Endocrinol Metab 2023; 109: 25-35
- 31 Douglas RS, Kahaly GJ, Patel A. et al. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med 2020; 382: 341-352
- 32 Douglas RS, Kahaly GJ, Ugradar S. et al. Teprotumumab Efficacy, Safety, and Durability in Longer-Duration Thyroid Eye Disease and Re-treatment: OPTIC-X Study. Ophthalmology 2022; 129: 438-449
- 33 Rosenblatt TR, Chiou CA, Yoon MK. et al. Proptosis Regression After Teprotumumab Treatment for Thyroid Eye Disease. Ophthalmic Plast Reconstr Surg 2024; 40: 187-191
- 34 Gulbins A, Horstmann M, Daser A. et al. Linsitinib, an IGF-1R inhibitor, attenuates disease development and progression in a model of thyroid eye disease. Front Endocrinol (Lausanne) 2023; 14: 1211473
- 35 Eckstein AK, Plicht M, Lax H. et al. Thyrotropin receptor autoantibodies are independent risk factors for Gravesʼ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab 2006; 91: 3464-3470
- 36 Stöhr M, Oeverhaus M, Lytton SD. et al. Predicting the Course of Gravesʼ Orbitopathy Using Serially Measured TSH-Receptor Autoantibodies by Automated Binding Immunoassays and the Functional Bioassay. Horm Metab Res 2021; 53: 435-443
- 37 Davis JB, Mudalegundi S, Henderson AD. et al. Stability of Ocular Alignment After Teprotumumab Therapy in a Cohort of Patients With Thyroid Eye Disease and Baseline Diplopia. J Neuroophthalmol 2024; 44: 527-532
