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Long-term outcomes in corticosteroid-refractory Graves' orbitopathy treated with tocilizumab
Laura Moi1, Mehrad Hamedani2, Camillo Ribi1
1Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland.
Background:
Up to 20% of patients with moderate to severe Graves' orbitopathy (GO) do not respond to high-dose glucocorticoids (GC). A few studies, including a randomized trial, have demonstrated the efficacy of interleukin-6 (IL-6) blockade with tocilizumab (TCZ) in GC-refractory GO. However, data on predictors of response to TCZ and long-term outcomes are lacking.
Methods:
Observational single-center study on ten consecutive patients treated with TCZ for GC-refractory GO, between 2016 and 2020. Median (interquartile range) follow-up was 24 (12-36) months.
Results:
Inflammation and exophthalmos improved dramatically in all patients within months after starting TCZ. Mean Clinical Activity Score decreased from 4.80 ± 1.13 to 0.70 ± 0.82 points at 6 months (mean change: -4.10 ± 1.52; p < .0001). Proptosis improved from 23.2 ± 2.1 to 20.6 ± 2.0 mm at 6 months (mean change: -2.9 ± 1.4 mm; p < .0001). Diplopia resolved in 7 patients. Thyroid receptor antibodies decreased markedly during TCZ treatment. Baseline serum IL-6 levels did not predict clinical response. TCZ was well-tolerated. During follow-up, 3 patients were diagnosed with cancer (breast cancer in 2 and urothelial cancer in 1).
Conclusions:
TCZ was rapidly effective and well-tolerated in our patients with GC-refractory GO. Four patients experienced mild/moderate adverse events as neutropenia, hyperlipidemia, and infections; nearly a third developed cancer during the follow-up. The increased incidence observed could be explained by the high prevalence of smokers, that are at higher risk for Graves' orbitopathy and solid malignancies as breast cancer. Thus, regular cancer screening could be proposed to this vulnerable population receiving high doses of immunosuppressants.
Insights
Tocilizumab (TCZ) effectively treats glucocorticoid-refractory Graves' orbitopathy (GO), improving inflammation and proptosis. While TCZ is well-tolerated, long-term monitoring for adverse events like cancer is recommended for patients with GO.
Area of Science:
- Ophthalmology
- Endocrinology
- Immunology
Background:
- Graves' orbitopathy (GO) affects moderate to severe cases, with 20% unresponsive to high-dose glucocorticoids (GC).
- Interleukin-6 (IL-6) blockade using tocilizumab (TCZ) shows promise in GC-refractory GO.
- Limited data exists on TCZ response predictors and long-term outcomes in GO.
Purpose of the Study:
- To evaluate the efficacy and safety of TCZ in patients with GC-refractory GO.
- To assess long-term outcomes and identify potential predictors of response to TCZ.
- To analyze adverse events associated with TCZ treatment in this population.
Main Methods:
- An observational, single-center study included ten consecutive patients with GC-refractory GO treated with TCZ from 2016-2020.
- Median follow-up duration was 24 months (range: 12-36 months).
- Clinical outcomes, including inflammation, proptosis, diplopia, and thyroid receptor antibodies, were monitored.
Main Results:
- All patients showed dramatic improvement in inflammation and exophthalmos within months of TCZ initiation.
- Mean Clinical Activity Score significantly decreased (p < .0001), and proptosis improved (p < .0001).
- Diplopia resolved in 7 patients, and thyroid receptor antibodies decreased; baseline IL-6 did not predict response. Three patients developed cancer during follow-up.
Conclusions:
- TCZ demonstrated rapid effectiveness and good tolerability in GC-refractory GO patients.
- Mild/moderate adverse events occurred, and a notable incidence of cancer was observed, potentially linked to smoking and immunosuppression.
- Regular cancer screening is advised for this high-risk population receiving TCZ.
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