Evaluación del grosor de los músculos extraoculares y la quemosis tras tocilizumab en oftalmopatía de Graves mediante tomografía de coherencia óptica

De‐Pablo‐Gómez‐de‐Liaño, Lucía; Fernández‐Vigo, José Ignacio; Troyano-Rivas, J.A.; Niño-Rueda, Cristina; Romo-López, Á.; Gómez-de-Liaño, R.

doi:10.1016/j.oftal.2018.04.011

Cited by 7 publications

(4 citation statements)

References 10 publications

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“…Tocilizumab was first introduced as a treatment for severe glucocorticoid-resistant GO in 2009, with the first results published in a small case series [18]. The efficacy of tocilizumab was later supported by a randomized clinical trial in patients with active steroid-resistant GO [19], as well as by several case reports and case series [20][21][22][23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Steroid-Resistant Graves’ Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience

Pérez-Moreiras¹,

Varela-Agra²,

Prada-Sánchez³

et al. 2021

JCM

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This study aimed to assess the effectiveness and safety of tocilizumab use for the treatment of active steroid-resistant Graves’ orbitopathy (GO). A retrospective longitudinal study was conducted by reviewing the medical records at a single center between November 2009 and December 2018. A total of 114 patients with steroid-resistant Graves’ orbitopathy were examined and treated with tocilizumab, of which 54 adults met the inclusion criteria. No concomitant medication for the treatment of orbitopathy was used. The main primary outcomes included changes from baseline in the Clinical Activity Score (CAS) and thyrotropin receptor antibody (TRAb) levels throughout therapy with tocilizumab. The absolute responses to treatment were defined as the achievement of CAS ≤ 1 and TRAb ≤ 10 U/L. A composite ophthalmic score including CAS, proptosis, eyelid retraction, and diplopia was used to evaluate individual improvement in GO. Adverse drug reactions were also assessed. Analysis of the patient’s CAS and TRAb levels showed meaningful reductions during tocilizumab treatment. Differences between values at baseline and subsequent time points were statistically significant (p < 0.001 for all comparisons). The absolute CAS response (CAS = 0 or 1) was achieved in 74% (37/50) of patients after the fourth dose of tocilizumab (at week 16), with a TRAb response being achieved in 55% (23/42) of patients. The relative CAS response (reduction ≥ 2 points) was achieved in 90.9% of patients (40/44) after the first dose of tocilizumab (at week 4). Measurements of proptosis (reduction ≥ 2 mm in 78% of patients, 42/54) and eyelid retraction (reduction ≥ 2 mm in 75%, 33/44), and the prevalence of diplopia (improvement in 68%, 19/28) were significantly reduced after the last dose of tocilizumab (p < 0.001 for all comparisons). GO improved in 98% (53/54) of patients when at least two criteria of the composite evaluation were required. Four patients exhibited disease recurrence, defined as an increase in CAS of ≥2 points in the six months following the date of inactivation. Most adverse drug reactions were mild or moderate in severity. In conclusion, our data suggest that a course of at least 4 months (one monthly dose) of tocilizumab therapy provides a significant benefit to patients with active moderate-to-severe steroid-resistant GO.

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Section: Introductionmentioning

confidence: 99%

Steroid-Resistant Graves’ Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience

Pérez-Moreiras¹,

Varela-Agra²,

Prada-Sánchez³

et al. 2021

JCM

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“…Therefore, features of RCTs may differ from those of clinical practice, which may modify the results of a specific treatment [ 17 ]. However, as discussed before, the studies on TCZ in GO in clinical practice are scarce and based on a small series of patients [ 15 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-IL-6 Receptor Tocilizumab in Refractory Graves’ Orbitopathy: National Multicenter Observational Study of 48 Patients

Sánchez-Bilbao

Martínez-López

Revenga

et al. 2020

JCM

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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.

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“…An amelioration of proptosis was reported in 13 patients, extraocular motility in 15, and 7/13 solved the problem of diplopia, with no relapse of GO at the end of the follow-up. These data suggested that tocilizumab might be effective in GO patients resistant to steroids (95). Furthermore, a reduction in extraocular muscle thickness and chemosis was reported after therapy with tocilizumab in patients with GO, by using an optical coherence tomography.…”

Section: Drugs Targeting Cytokines In Gd and Gomentioning

confidence: 77%

“…Tocilizumab is a humanized mAb recognizing the IL-6R, which attained the approval in Castleman's disease, systemic juvenile idiopathic arthritis, and RA. A prospective nonrandomized study has been conducted in 18 GO patients (refractory to CS) treated with tocilizumab (95). An amelioration of proptosis was reported in 13 patients, extraocular motility in 15, and 7/13 solved the problem of diplopia, with no relapse of GO at the end of the follow-up.…”

Section: Drugs Targeting Cytokines In Gd and Gomentioning

confidence: 99%

Cytokines as Targets of Novel Therapies for Graves’ Ophthalmopathy

et al. 2021

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Graves’ disease (GD) is an organ-specific autoimmune disorder of the thyroid, which is characterized by circulating TSH-receptor (TSH-R) stimulating antibodies (TSAb), leading to hyperthyroidism. Graves’ ophthalmopathy (GO) is one of GD extra-thyroidal manifestations associated with the presence of TSAb, and insulin-like growth factor-1 receptor (IGF-1R) autoantibodies, that interact with orbital fibroblasts. Cytokines are elevated in autoimmune (i.e., IL-18, IL-6) and non-autoimmune hyperthyroidism (i.e., TNF-α, IL-8, IL-6), and this could be associated with the chronic effects of thyroid hormone increase. A prevalent Th1-immune response (not related to the hyperthyroidism per se, but to the autoimmune process) is reported in the immune-pathogenesis of GD and GO; Th1-chemokines (CXCL9, CXCL10, CXCL11) and the (C-X-C)R3 receptor are crucial in this process. In patients with active GO, corticosteroids, or intravenous immunoglobulins, decrease inflammation and orbital congestion, and are considered first-line therapies. The more deepened understanding of GO pathophysiology has led to different immune-modulant treatments. Cytokines, TSH-R, and IGF-1R (on the surface of B and T lymphocytes, and fibroblasts), and chemokines implicated in the autoimmune process, are possible targets of novel therapies. Drugs that target cytokines (etanercept, tocilizumab, infliximab, adalimumab) have been tested in GO, with encouraging results. The chimeric monoclonal antibody directed against CD20, RTX, reduces B lymphocytes, cytokines and the released autoantibodies. A multicenter, randomized, placebo-controlled, double-masked trial has investigated the human monoclonal blocking antibody directed against IGF-1R, teprotumumab, reporting its effectiveness in GO. In conclusion, large, controlled and randomized studies are needed to evaluate new possible targeted therapies for GO.

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Evaluación del grosor de los músculos extraoculares y la quemosis tras tocilizumab en oftalmopatía de Graves mediante tomografía de coherencia óptica

Cited by 7 publications

References 10 publications

Steroid-Resistant Graves’ Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience

Steroid-Resistant Graves’ Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience

Anti-IL-6 Receptor Tocilizumab in Refractory Graves’ Orbitopathy: National Multicenter Observational Study of 48 Patients

Cytokines as Targets of Novel Therapies for Graves’ Ophthalmopathy

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