Subcutaneous Tocilizumab for Thyroid Eye Disease: Simplified Dosing and Delivery

Copperman, Thomas S; Idowu, Oluwatobi O; Kersten, Robert C.; Vagefi, M. Reza

doi:10.1097/iop.0000000000001346

Cited by 25 publications

(31 citation statements)

References 9 publications

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“…Tocilizumab has also been reported to be effective when administered subcutaneously in 4 biweekly doses over 8 weeks. 52 Tumor necrosis factor alpha (TNF-) inhibitors include etanercept, adalimumab and infliximab.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Teprotumumab

Winn

Kersten

2021

Ophthalmology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Teprotumumab

Winn

Kersten

2021

Ophthalmology

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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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“… 83 Tocilizumab therapy consists of four infusions given every 4 weeks for a total of 16 weeks, although subcutaneous injections have also been tried and found to be effective. 84 A randomized clinical trial showed that tocilizumab significantly reduced CAS by 2 points or greater in 93% of patients with moderate-to-severe, corticosteroid-resistant TED at week 16 versus 59% in the placebo group. 70 There was no improvement in diplopia.…”

Section: Management For Active Tedmentioning

confidence: 99%

Updates on the understanding and management of thyroid eye disease

2021

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Thyroid eye disease (TED) is a complex disease associated with myriad clinical presentations, including facial disfigurement, vision loss, and decreased quality of life. Traditionally, steroid therapy and/or radiation therapy were commonly used in the treatment of active TED. While these therapies can help reduce inflammation, they often do not have a sustainable, significant long-term effect on disease outcomes, including proptosis and diplopia. Recent advances in our understanding of the pathophysiology of TED have shifted the focus of treatment toward targeted biologic therapies. Biologics have the advantage of precise immune modulation, which can have better safety profiles and greater efficacy compared to traditional approaches. For instance, the insulin-like growth factor-1 receptor (IGF-1R) has been found to be upregulated in TED patients and to colocalize with the thyroid-stimulating hormone receptor (TSHR), forming a signaling complex. Teprotumumab is an antibody targeted against IGF-1R. By inhibiting the IGF-1R/TSHR signaling pathway, teprotumumab may reduce the production of proinflammatory cytokines, hyaluronan secretion, and orbital fibroblast activation in patients with TED. Due to promising phase II and III clinical trial results, teprotumumab has become the first biologic US Food and Drug Administration (FDA)-approved for the treatment of TED. In addition, there are currently ongoing studies looking at the use of antibodies targeting the neonatal Fc receptor (FcRn) in various autoimmune diseases, including TED. FcRn functions to transport immunoglobulin G (IgG) and prevent their lysosomal degradation. By blocking the recycling of IgG, this approach may dampen the body’s immune response, in particular the pathogenic IgG implicated in some autoimmune diseases. Advances in our understanding of the pathophysiology of TED, therefore, are leading to more targeted therapeutic options, and we are entering an exciting new phase in the management of TED. This review will cover recent insights into the understanding of TED pathophysiology and novel treatment options as well as ongoing studies of new potential treatment options for TED.

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Subcutaneous Tocilizumab for Thyroid Eye Disease: Simplified Dosing and Delivery

Cited by 25 publications

References 9 publications

Teprotumumab

Teprotumumab

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

Updates on the understanding and management of thyroid eye disease

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