scholarly journals Predictive score for the development or progression of Graves’ orbitopathy in patients with newly diagnosed Graves’ hyperthyroidism

2018 ◽  
Vol 178 (6) ◽  
pp. 635-643 ◽  
Author(s):  
Wilmar Wiersinga ◽  
Miloš Žarković ◽  
Luigi Bartalena ◽  
Simone Donati ◽  
Petros Perros ◽  
...  
Keyword(s):  
Prospective Observational Study ◽  
Subsequent Treatment ◽  
Current Smoker ◽  
Predictive Score ◽  
Antithyroid Drugs ◽  
Clinical Activity ◽  
Newly Diagnosed ◽  
Predictive Values ◽  
If Current ◽  
Graves Orbitopathy

Objective To construct a predictive score for the development or progression of Graves’ orbitopathy (GO) in Graves’ hyperthyroidism (GH). Design Prospective observational study in patients with newly diagnosed GH, treated with antithyroid drugs (ATD) for 18 months at ten participating centers from EUGOGO in 8 European countries. Methods 348 patients were included with untreated GH but without obvious GO. Mixed effects logistic regression was used to determine the best predictors. A predictive score (called PREDIGO) was constructed. Results GO occurred in 15% (mild in 13% and moderate to severe in 2%), predominantly at 6–12 months after start of ATD. Independent baseline determinants for the development of GO were clinical activity score (assigned 5 points if score > 0), TSH-binding inhibitory immunoglobulins (2 points if TBII 2–10 U/L, 5 points if TBII > 10 U/L), duration of hyperthyroid symptoms (1 point if 1–4 months, 3 points if >4 months) and smoking (2 points if current smoker). Based on the odds ratio of each of these four determinants, a quantitative predictive score (called PREDIGO) was constructed ranging from 0 to 15 with higher scores denoting higher risk; positive and negative predictive values were 0.28 (95% CI 0.20–0.37) and 0.91 (95% CI 0.87–0.94) respectively. Conclusions In patients without GO at diagnosis, 15% will develop GO (13% mild, 2% moderate to severe) during subsequent treatment with ATD for 18 months. A predictive score called PREDIGO composed of four baseline determinants was better in predicting those patients who will not develop obvious GO than who will.

scholarly journals MANAGEMENT OF ENDOCRINE DISEASE: Predictive scores in autoimmune thyroid disease: are they useful?

2019 ◽  
Vol 181 (3) ◽  
pp. R119-R131 ◽  
Author(s):  
Grigoris Effraimidis
Keyword(s):  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Prediction Models ◽  
Prediction Score ◽  
Predictive Score ◽  
Antithyroid Drugs ◽  
Newly Diagnosed ◽  
Endocrine Disease ◽  
Autoimmune Thyroid ◽  
Graves Orbitopathy

Prediction models are of a great assistance for predicting the development of a disease, detecting or screening undiagnosed patients, predicting the effectiveness of a treatment and helping toward better decision-making. Recently, three predictive scores in the field of autoimmune thyroid disease (AITD) have been introduced: The Thyroid Hormones Event Amsterdam (THEA) score: a predictive score of the development of overt AITD, the Graves’ Events After Therapy (GREAT) score: a prediction score for the risk of recurrence after antithyroid drugs withdrawal and the Prediction Graves’ Orbitopathy (PREDIGO) score: a prediction score for the development of Graves’ orbitopathy in newly diagnosed patients with Graves’ hyperthyroidism. Their construction, clinical applicability, the possible preventative measurements which can be taken to diminish the risks and the potential future developments which can improve the accuracy of the predictive scores are discussed in this review.

scholarly journals IgG4 as a Biomarker in Graves’ Orbitopathy

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Michał Olejarz ◽  
Ewelina Szczepanek-Parulska ◽  
Daniela Dadej ◽  
Nadia Sawicka-Gutaj ◽  
Remigiusz Domin ◽  
...  
Keyword(s):  
Clinical Features ◽  
Thyroid Disease ◽  
Elevated Serum ◽  
Antithyroid Drugs ◽  
Clinical Activity ◽  
Inflammatory Disorder ◽  
Autoimmune Thyroid Diseases ◽  
Immunoglobulin G4 ◽  
Serum Igg4 ◽  
Graves Orbitopathy

Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory disorder associated with fibrosis and abundant tissue lymphoplasmacytic infiltrations. It typically affects the pancreas, the salivary glands, and the retroperitoneal space. However, it might also involve multiple other organs, including the orbit and the thyroid. Recent studies have suggested that IgG4 plays a role in the pathophysiology of autoimmune thyroid diseases. This ultimately led to the establishment of new clinical entities called IgG4-related thyroid disease and thyroid disease with an elevation of IgG4. The aim of this paper is to describe the pathophysiological, histopathological, and clinical features of Graves’ Disease (GD) and Graves’ Orbitopathy (GO) with elevated IgG4 levels. Multiple studies have demonstrated higher IgG4 serum concentrations in GD patients than in healthy euthyroid controls. Depending on the studied population, elevated serum IgG4 levels occur in 6.4-23% (average: 10.3%) of all patients with GD, 8.3-37.5% (average: 17.6%) of patients with GO, and 0-9.8% (average: 5.4%) of patients with GD without GO, while GO patients comprise 37.5-100% (average: 65.8%) of all GD patients with elevated IgG4 levels. Characteristic features of GD with elevated IgG4 levels include lower echogenicity of the thyroid gland on ultrasound examination, peripheral blood eosinophilia, higher prevalence of orbitopathy, and better response to antithyroid drugs with a tendency to develop hypothyroidism when compared to patients with GD and normal levels of IgG4. Typical signs of GO accompanied by increased concentration of IgG4 include younger age at diagnosis, and more severe course of the disease with a higher Clinical Activity Score (CAS).. We strongly recommend considering the diagnosis of GO with elevated IgG4 in patients with an established diagnosis of GD, elevated serum IgG4 levels, and clinical features of ophthalmic disease overlapping with those of IgG4-related orbital disease.

scholarly journals THE 2021 EUROPEAN GROUP ON GRAVES’ ORBITOPATHY (EUGOGO) CLINICAL PRACTICE GUIDELINES FOR THE MEDICAL MANAGEMENT OF GRAVES’ ORBITOPATHY

2021 ◽  
Author(s):  
Luigi Bartalena ◽  
George J. Kahaly ◽  
Lelio Baldeschi ◽  
Colin M Dayan ◽  
Anja Eckstein ◽  
...  
Keyword(s):  
Risk Factors ◽  
Oral Prednisone ◽  
High Serum ◽  
Patient Choice ◽  
Current Evidence ◽  
Antithyroid Drugs ◽  
Clinical Activity ◽  
Orbital Decompression ◽  
Choice Of Treatment ◽  
Graves Orbitopathy

Graves’ orbitopathy (GO) is the main extrathyroidal manifestation of Graves’ disease (GD). Choice of treatment should be based on assessment of clinical activity and severity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smoking, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments and selenium (selenium-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight threatening GO, antithyroid drugs are preferred when managing Graves’ hyperthyroidism. In moderate-to-severe and active GO, intravenous (iv) glucocorticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safety profile, costs and reimbursement, drug availability, long-term effectiveness and patient choice after extensive counselling, a combination of iv methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 grams (g) of iv methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, higher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplopia. Second-line treatments for moderate-to-severe and active GO include: a) a second course of iv methylprednisolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; c) orbital radiotherapy combined with oral or iv glucocorticoids, d) teprotumumab; e) rituximab and f) tocilizumab. Sight threatening GO is treated with several high single doses of iv methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint and eyelid surgery) is indicated for inactive residual GO manifestations.

scholarly journals Machine learning using clinical data at baseline predicts the efficacy of vedolizumab at week 22 in patients with ulcerative colitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jun Miyoshi ◽  
Tsubasa Maeda ◽  
Katsuyoshi Matsuoka ◽  
Daisuke Saito ◽  
Sawako Miyoshi ◽  
...  
Keyword(s):  
Machine Learning ◽  
Ulcerative Colitis ◽  
Prediction Model ◽  
Clinical Features ◽  
Unmet Need ◽  
Patient Treatment ◽  
Clinical Activity ◽  
Prediction Tool ◽  
Real World Data ◽  
Predictive Values

AbstractPredicting the response of patients with ulcerative colitis (UC) to a biologic such as vedolizumab (VDZ) before administration is an unmet need for optimizing individual patient treatment. We hypothesized that the machine-learning approach with daily clinical information can be a new, promising strategy for developing a drug-efficacy prediction tool. Random forest with grid search and cross-validation was employed in Cohort 1 to determine the contribution of clinical features at baseline (week 0) to steroid-free clinical remission (SFCR) with VDZ at week 22. Among 49 clinical features including sex, age, height, body weight, BMI, disease duration/phenotype, treatment history, clinical activity, endoscopic activity, and blood test items, the top eight features (partial Mayo score, MCH, BMI, BUN, concomitant use of AZA, lymphocyte fraction, height, and CRP) were selected for logistic regression to develop a prediction model for SFCR at week 22. In the validation using the external Cohort 2, the positive and negative predictive values of the prediction model were 54.5% and 92.3%, respectively. The prediction tool appeared useful for identifying patients with UC who would not achieve SFCR at week 22 during VDZ therapy. This study provides a proof-of-concept that machine learning using real-world data could permit personalized treatment for UC.

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

2021 ◽  
Vol 10 (4) ◽  
pp. 706
Author(s):  
José V. Pérez-Moreiras ◽  
María Varela-Agra ◽  
M. Consuelo Prada-Sánchez ◽  
Guillermo Prada-Ramallal
Keyword(s):  
Adverse Drug Reactions ◽  
Disease Recurrence ◽  
Clinical Activity ◽  
Eyelid Retraction ◽  
Single Center ◽  
Drug Reactions ◽  
Steroid Resistant ◽  
Single Center Experience ◽  
Graves Orbitopathy ◽  
The Absolute

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.

scholarly journals AB1027 EFFECTIVENESS OF SUBCUTANEOUS ANTI-INTERLEUCINE 6 TREATMENT IN PATIENTS WITH ACTIVE MODERATE-SEVERE GRAVES’ ORBITOPATHY REFRACTORY TO CONVENTIONAL THERAPY.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1806.2-1806
Author(s):  
L. Fernández de la Fuente Bursón ◽  
F. J. Toyos Sáenz de Miera ◽  
D. Ruiz-Montesinos ◽  
M. Gessa Sorroche ◽  
M. C. Díaz Ruiz ◽  
...  
Keyword(s):  
Demographic Data ◽  
Case Series ◽  
Multicenter Trial ◽  
Smoking History ◽  
Clinical Aspects ◽  
Clinical Activity ◽  
Nonsurgical Management ◽  
Usual Clinical Practice ◽  
Antithyroid Treatment ◽  
Graves Orbitopathy

Background:Graves’ Orbitopathy (OG) is the main extrathyroid manifestation of Graves’ disease (GD). Up to 25% of patients have moderate-severe inflammatory activity with a risk of major sequelae. Intravenous (i.v.) glucocorticoids (GC) pulses are the standard therapy. In refractory cases, several classic and some biological immunosuppressantsare used, obtaining variable responses. Interleukin 6 (IL6) is involved in the pathogenesis of OG, which has justified the off-label treatment with Tocilizumab (TCZ)1, whose use by route i.v. has shown favorable results in published small case series and a single multicenter trial2.Objectives:To analyse the ocular effectiveness of anti-IL6 therapy used subcutaneously (s.c.) in patients with moderate-severe active refractory OG in usual clinical practice.Methods:Retrospective descriptive observational study of a series of cases of moderate-severe OG patients treated with anti-IL6 s.c. The patient medical records of those who had received at least 1 cycle of anti-IL6 treatment were reviewed (December 2013-December 2019). The primary effectiveness outcome was the change of the Clinical Activity Score (CAS). Favorable response was considered: reduction of CAS≥2 points together with obtaining inactivity (CAS <3). Demographic data, personal medical history, clinical aspects of GD, previous therapies and data on the use and safety of anti-IL6 were collected. The SPSS11 package was used for statistical analysis, using non-parametric tests for quantitative variables. The study was approved by the local Ethical Committee.Results:12 of the 15 patients (80%) were women with a mean of 50.27 years (21-72). 60% (n=9) had smoking history, 40% (n=6) active. 26.7% (n=4) were diabetic, all without retinopathy. 100% of patients received imidazole antithyroid treatment. 46.7% (n=7) required β-blockers and 20% (n=3) diuretics. 66.7% thyroidectomy (n=10) and 20% (n=3) decompressive eye surgery and/or blepharoplasty were performed. Thyroid and ocular radiotherapy were used in 2 patients. 3 patients received botox. 80% (n=12) of them had previously received GC. 93.3% (n=14) were naïve to biological therapy, only 1 patient previously used Rituximab. All except one patient who was treated with SRL received TCZ as IL6 therapy. A significant favorable response was obtained in 100% of the patients (p=0.008), decreasing CAS average from 4.9 (2-7) to 1.7 (0-2) at the end of the therapy [Figure 1]. The severity of the OG changed from being moderate in 72.7% of the patients to mild in 66.7% of the total. The median time to inactivity was 8 months (2-15). 73.3% (n=11) of the patients finished the treatment reaching inactive OG, the rest (although inactive) maintained therapy. After 6 months, 100% of those who completed the treatment remained inactive with average CAS of 1.3 (0-2). Smoking did not influence the response, nor any other variable collected. Adverse events appeared in 26.7% (n=4) of the cases, all of them mild and without widrawal.Conclusion:Treatment with anti-IL6 s.c. steadily decreases the clinical activity measured by CAS in patients with moderate-severe refractory OG, despite poor prognosis factors (such as smoking), with a good safety profile.References:[1]Taylor PN, Zhang L, Lee RWJ, Muller I, Ezra DG, Dayan CM, et al. New insights into the pathogenesis and nonsurgical management of Graves’ orbitopathy. Nat Rev Endocrinol. 2020 Feb;16(2):104-116.[2]Perez-Moreiras JV, Gomez-Reino JJ, Maneiro JR, Perez-Pampin E, Romo Lopez A, Rodríguez Álvarez FM, et al. Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Gravesˊ Orbitopathy: A Randomized Clinical Trial. Am J Ophthalmol. 2018;195:181–90.Disclosure of Interests:None declared

The combination of venetoclax, lenalidomide, and rituximab in patients with newly diagnosed mantle cell lymphoma induces high response rates and MRD undetectability.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7505-7505
Author(s):  
Tycel Jovelle Phillips ◽  
Alexey Valeryevich Danilov ◽  
David Alan Bond ◽  
Alex Francisco Herrera ◽  
Kami J. Maddocks ◽  
...  
Keyword(s):  
Phase 1 ◽  
Safety Data ◽  
Standard Of Care ◽  
Primary Objective ◽  
Clinical Activity ◽  
Newly Diagnosed ◽  
Grade 5 ◽  
Unrelated Condition ◽  
Mantle Cell ◽  
Grade 3

7505 Background: MCL is a rare lymphoma without a standard of care but several regimens have demonstrated clinical activity, the majority based on traditional chemotherapy. We hypothesized that adding venetoclax (V) to R2 would be safe and effective in MCL pts irrespective of age, morphology or stage. Here we present safety and efficacy data from the on-going phase 1b study of R2 + V in pts with newly diagnosed MCL. Methods: This multi-center phase 1 study (NCT03523975) enrolled pts aged ≥18 yrs with untreated MCL. The primary objective was to characterize the safety and tolerability of R2 + V and determine the MTD. During induction (12 months (m)) pts received lenalidomide (L) 20 mg daily on day 1-21, Rituximab (R) was given weekly during c1 then on day 1 of every even cycle, V was escalated over 4 weeks to 400 mg beginning day 8. Each cycle is 28 days (d). The DLT period was 42 d beginning C1D8. In maintenance, R every 8 weeks for 36m, L at 10 mg or half of last dose during induction for 24 m and V for minimum 12 m. No pts have been transplanted. Pts with progression (PD) came off study. MRD was analyzed in parallel with scans during induction by clonoSEQ assay (Adaptive Biotechnologies). Results: As of Feb. 1st, 2021, we have enrolled all 28 planned pts on study. Pt characteristics/responses are summarized in Table. Among the 28 pts who have received at least one dose, the median treatment duration so far is 278d (IQR 170-560), with 24 pts still on treatment (Tx). 1 pt is off from a unrelated condition. All pts escalated to V 400 mg w/o any DLTs noted. Treatment-emergent adverse events (TEAEs) were reported in 100% of pts, and grade 3+ TEAEs were reported in 26 (93%) patients. The most common all-grade TEAEs (≥50% of pts), regardless of relationship to study Tx, were fatigue, neutropenia and diarrhea. Grade ≥3 TEAEs reported in ≥50% pts were neutropenia (68%) and thrombocytopenia (50%). No pts have withdrawn or d/c Tx due to AEs. There was one grade 5 event, in a non-evaluable pt, related to a PE that occurred prior to DLT period. In the 28 evaluable pts the ORR (CR/PR) was 96% (27/28 pts) with CR/CRu of 89%. Of the responding pts, two had PD, one w/ CR and one w/ PR. All pts with PD had baseline TP53 mutation. MRD testing was successful in all pts. At time of submission 20 of 28 (71%) were MRD - at 10-6. Conclusions: Interim results show that at the MTD the combination of V 400 mg daily, L 20 mg, with R is safe with a manageable toxicity profile and a high ORR and MRD - in pts with newly diagnosed MCL. Safety data is consistent with the AE profile noted for each drug without any unexpected or unique AEs. Updated results including BH3 profiling will be presented at the meeting. Clinical trial information: NCT03523975. [Table: see text]

Graves’ Orbitopathy: Extraocular Muscle/Total Orbit Area Ratio is Positively Related to the Clinical Activity Score

2011 ◽  
Vol 22 (3) ◽  
pp. 301-308 ◽  
Author(s):  
Rosario Le Moli ◽  
Alessandro Pluchino ◽  
Vincenzo Muscia ◽  
Concetto Regalbuto ◽  
Bruno Luciani ◽  
...  
Keyword(s):  
Extraocular Muscle ◽  
Area Ratio ◽  
Activity Score ◽  
Clinical Activity ◽  
Clinical Activity Score ◽  
Graves Orbitopathy

scholarly journals SAT-500 Response to Tocilizumab Retreatment in Refractory Thyroid Eye Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Daniel Kaplan ◽  
Benjamin Erickson ◽  
Andrea Kossler ◽  
Julie Chen ◽  
Chrysoula Dosiou
Keyword(s):  
Controlled Trial ◽  
Standard Of Care ◽  
Thyroid Eye Disease ◽  
Eye Disease ◽  
Clinical Activity ◽  
Current Standard ◽  
Compressive Optic Neuropathy ◽  
Effective Option ◽  
Graves Orbitopathy ◽  
Recurrent Inflammation

Abstract Background: The current standard of care for moderate to severe thyroid eye disease (TED) is intravenous methylprednisolone (IVMP), though alternative immunosuppressive options are emerging. In a recent randomized trial, Tocilizumab (TCZ), an anti-IL-6 receptor antibody, demonstrated improved efficacy for corticosteroid-resistant TED compared to placebo. Clinical response to TCZ retreatment, however, has not been previously reported. Clinical case: A 64-year old man presented with progressive diplopia, eyelid retraction and edema and retrobulbar pain. Initial labs revealed TSH 0.221 uIU/mL, free thyroxine (FT4) 1.11 ng/dL, total T3 172 ng/dL and a thyroid stimulating immunoglobulin (TSI) index of 329 (normal &lt; 140). The patient was a former cigarette smoker who had recently transitioned to e-cigarettes. He was treated with 12 weeks of IVMP with improvement in ocular redness and swelling. Three months following completion of treatment, he presented with worsening left sided proptosis, restrictive strabismus, and compressive optic neuropathy (CON) evidenced by deteriorating central acuity and color vision. He underwent urgent surgical decompression for CON with full restoration of visual acuity. He then received a second 12-week course of IVMP with concomitant orbital radiation. Of note, his hyperthyroidism was well controlled with methimazole. Two months after his second IVMP course, he had a third flare of ophthalmic symptoms. He was then treated with TCZ 8 mg/kg (800mg) IV monthly for six months. The patient’s Clinical Activity Score (CAS) improved from 4 to 2 and TSI index decreased from 610 to 92 (normal). He had significant improvement in periorbital edema, caruncle/plica swelling, and conjunctival injection. However, ten months following completion of the TCZ course he again complained of worsening diplopia and left proptosis. Of note, relapse of his TED symptoms was preceded by an increase in TSI from 92 to 300 two months prior. Orbital CT demonstrated progression of left orbitopathy and increased orbital apex crowding. Following these CT findings he was restarted on TCZ, of which he has now completed 5 additional infusions. His CAS has improved from 3 to 2 and TSI index has decreased from 284 to 100. Conclusion: This is the first reported case of response to successive courses of TCZ in relapsing, severe, corticosteroid-resistant TED. TCZ can be an effective option for refractory TED though retreatment may be necessary for recurrent inflammation. Further study of TCZ is required to determine its role in relapsing TED and the optimal duration of therapy needed. References: Perez-Moreiras et al., 2018. Efficacy of Tocilizumab in patients with moderate to severe corticosteroid resistant Graves’ orbitopathy: a randomized controlled trial. Am J Ophthalmol 195:181

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

2020 ◽  
Vol 9 (9) ◽  
pp. 2816
Author(s):  
Lara Sánchez-Bilbao ◽  
David Martínez-López ◽  
Marcelino Revenga ◽  
Ángel López-Vázquez ◽  
Elia Valls-Pascual ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Disease Activity ◽  
Therapeutic Option ◽  
Clinical Activity ◽  
Open Label ◽  
Serious Adverse Events ◽  
Low Disease Activity ◽  
Multicenter Observational Study ◽  
Graves Orbitopathy ◽  
One Year

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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