Successful Treatment for Severe Thyroid-associated Ophthalmopathy with Tocilizumab

Cañas, Carlos A.; Bonilla-Abadía, Fabio; Vallejo, Katherine; Rengifo, Hector M.; Gallon, Marco A.; Tobón, Gabriel J.

doi:10.2174/1871530318666180702150243

Cited by 13 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The severity of the inflammatory process positively correlated with TNF- α mRNA and IL-6 mRNA expression and negatively with IL-4 mRNA and IL-10 mRNA expression [ 28 ]. Furthermore, some pathways were already used in clinical trials: tocilizumab [interleukin-6 (IL-6) receptor antibodies] [ 6 ] and teprotumumab (monoclonal antibody being an inhibitor of insulin-like growth factor I receptor) [ 7 ]. The results of mentioned trials are very promising.…”

Section: Discussionmentioning

confidence: 99%

“…The main treatment option for GO is therapy with corticosteroids. In the last few years, some new methods were applied to treat GO: rituximab (a monoclonal antibody against the protein CD20 on the surface of B cells) [ 5 ], tocilizumab [interleukin-6 (IL-6) receptor antibodies] [ 6 ], and teprotumumab (monoclonal antibody being an inhibitor of insulin-like growth factor I receptor) [ 7 ]. They resulted from recently discovered new immune pathways which provided a basis to develop new treatment options.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of IL-29 in Euthyroid Patients with Graves’ Orbitopathy: A Preliminary Study

Falkowski

Szczepanek‐Parulska

Sawicka‐Gutaj

et al. 2020

Mediators of Inflammation

View full text Add to dashboard Cite

Background. The most frequent cause of hyperthyroidism is Graves’ disease (GD). Orbitopathy is the most prevalent and recognizable extrathyroidal manifestation of Graves’ disease with unrevealed pathogenesis. Interleukin 29 (IL-29) is a relatively newly discovered inflammatory cytokine. Thus, the aim of this study was to evaluate the relationship between IL-29 and Graves’ orbitopathy (GO) in euthyroid patients. Methods. Thirty-one euthyroid patients with Graves’ disease and with active GO [clinical activity score CAS≥3/7], seventeen euthyroid patients with GD but without GO, and seventy-two healthy control subjects (CS) matched for age and gender were enrolled in the study. The following parameters were evaluated in every participant: thyroid-related hormones and autoantibodies and inflammatory markers (white blood cells, hsCRP). ELISA assay was applied to measure the concentration of IL-29. Results. We found higher level of IL-29 in GO group in comparison with CS [165 (133-747) vs. 62 (62-217) pg/mL, p<0.001]. Furthermore, participants in the subgroup with GD with GO as compared with GD without GO had higher concentration of IL-29 [165 (133-747) vs. 62 (62-558) pg/mL, p=0.031]. The ROC analysis for IL-29 revealed IL-29 cut-off of 105 pg/mL (sensitivity 1.000 and specificity 0.597) as the best value significantly indicating the presence of GO in GD [area under the ROC curve (AUC): 0.739, 95% confidence interval (CI): 0.646-0.833, p<0.001]. Conclusions. The present study revealed for the first time an elevated level of IL-29 in the serum of patients with GD and GO that might suggest its involvement in the pathogenesis of GD ocular complications.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of IL-29 in Euthyroid Patients with Graves’ Orbitopathy: A Preliminary Study

Falkowski

Szczepanek‐Parulska

Sawicka‐Gutaj

et al. 2020

Mediators of Inflammation

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

Successful Treatment for Severe Thyroid-associated Ophthalmopathy with Tocilizumab

Abstract: Tocilizumab could be an optional treatment in patients with TAO.

Cited by 13 publications

References 0 publications

Evaluation of IL-29 in Euthyroid Patients with Graves’ Orbitopathy: A Preliminary Study

Evaluation of IL-29 in Euthyroid Patients with Graves’ Orbitopathy: A Preliminary Study

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

Contact Info

Product

Resources

About