Abstract
Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD). Our aim was to assess the efficacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves’ Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes); mean age ± standard deviation 51 ± 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved; BCVA (0.78 ± 0.25 vs. 0.9 ± 0.16; p = 0.0001), CAS (4.64 ± 1.5 vs. 1.05 ± 1.27; p = 0.0001) and intraocular pressure (IOP) (19.05 ± 4.1 vs. 16.73 ± 3.4 mmHg; p = 0.007). After a mean follow-up of 16.1 ± 2.1 months, low disease activity (CAS ≤ 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or inefficacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.
Highlights
Graves’ orbitopathy (GO) is an autoimmune inflammatory complication of Graves’ disease (GD).GO is characterized by the enlargement of the extraocular muscles and increase in fatty or orbit connective tissue volume [1,2,3]
The diagnosis of GD was based on the presence of some typical clinical features such as the presence of goiter, abnormal thyroid function tests and the presence of raised concentrations of thyroid stimulating hormone receptor (TSH-R) antibodies [24,25]
We cannot exclude that the use of MTX or AZA yielded some beneficial effect in the three patients who received these conventional immunosuppressors, our study showed a rapid and maintained improvement in all main outcomes following TCZ therapy (Figure 1; Figure 2)
Summary
Graves’ orbitopathy (GO) is an autoimmune inflammatory complication of Graves’ disease (GD). GO is characterized by the enlargement of the extraocular muscles and increase in fatty or orbit connective tissue volume [1,2,3]. GO is the most common extrathyroidal manifestation of GD, appearing in 25–70% of patients with this disease [4,5,6]. In mild forms (95% of patients) treatment consists of local therapy or systemic glucocorticoids. In moderate to severe cases systemic glucocorticoids are combined with immunosuppressive drugs [2,4]. GO may be a severe and urgent sight-threatening condition when dysthyroid optic neuropathy (DON) or corneal ulcerations are present [5]. DON must be immediately treated with intravenous (IV) glucocorticoids and, in some cases, with surgery [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
