Teprotumumab reduces extraocular muscle and orbital fat volume in thyroid eye disease

PurposeThyroid eye disease (TED) is a progressive, debilitating and potentially vision-threatening autoimmune disease. Teprotumumab, a novel human monoclonal antibody, has been shown to reverse the clinical manifestations of TED. Patients receiving teprotumumab have been shown in two multicenter, randomized placebo-controlled trials to have decreased proptosis, diplopia and inflammation after 24 weeks of treatment. This study aims to analyse volumetric and inflammatory changes on orbital imaging prior to and after teprotumumab treatment from one of these trials.DesignRetrospective review.SubjectsSix patients enrolled in the phase III teprotumumab clinical trial (OPTIC, NCT03298867) with active TED who received 24 weeks of teprotumumab and had pre- and post-treatment orbital imaging (CT or MRI). Additionally, 12 non-TED patients (24 orbits) were analysed as a comparative control group.Methods3D volumetric calculations of the extraocular muscles (EOMs), orbital fat, and bony orbit were measured using previously validated image processing software. 3D volumetric results and changes in EOM inflammation were compared with clinical measurements of TED.ResultsTotal EOM volume within each orbit was markedly reduced post-teprotumumab in all patients (n=six patients, 12/12 orbits, p<0.02). There was no statistical difference in post-treatment EOM volume when compared to non-TED controls. Total orbital fat volume was also reduced in 11 of 12 studied orbits (n=six patients, p=0.04). Overall EOM inflammation based on MRI signal intensity ratio was reduced in 8/8 orbits (n=four patients, p<0.01).ConclusionOrbital imaging demonstrated decreased EOM volumes and orbital fat tissue volumes after teprotumumab treatment.

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Orbital fat expansion in thyroid eye disease is related to age

European Journal of Ophthalmology ◽

10.1177/1120672119852322 ◽

2019 ◽

Vol 30 (5) ◽

pp. 1004-1007 ◽

Cited By ~ 1

Author(s):

Shoaib Ugradar ◽

Daniel B Rootman

Keyword(s):

Standard Deviation ◽

Muscle Volume ◽

Thyroid Eye Disease ◽

Secondary Outcome ◽

Eye Disease ◽

Decompression Surgery ◽

Analysis Tool ◽

Orbital Fat ◽

Orbital Volume ◽

Fat Volume

Purpose: To objectively measure the differential expansion of orbital fat and muscle volume in patients with thyroid eye disease. Methods: In this retrospective study, eligible participants were adults with clinical evidence of thyroid eye disease and high-resolution computed tomography scans of their orbits. Patients with a history of decompression surgery and/or medical or other conditions that could alter the orbital anatomy were excluded. Three dimensional reconstructions of the orbits allowed the calculation of the fat volume, muscle volume and bony orbital volume using the MIMICS imaging analysis tool. Both orbits from each patient were included without bias through the use of the generalized estimating equation. The primary outcome was the measurement of fat volume. Secondary outcome measures included the correlation of the muscle volume, bony orbital volume and exophthalmometry with age. Results: Fifty patients with thyroid eye disease who were included contributed 100 orbits. The sample included 29 females (age 57, standard deviation = 14.8) and 21 males (age 52, standard deviation = 18.14). Mean (standard deviation) exophthalmometry measurement was 21.58 (4.01). Fat volume and exophthalmometry were negatively correlated with age (p = 0.00001 and p = 0.00001, respectively). Muscle volume (p = 0.985) and bony orbital volume (p = 0.484) did not correlate with age. Conclusion: Older patients with thyroid eye disease have less expansion of fat volume compared with younger patients. There are no associations between age and the bony orbital volume or muscle volume. These results support the growing body of evidence which suggests that the pathophysiology of TED is different in older patient.

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Self-reported visual dysfunction in multiple sclerosis: results from the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25)

Multiple Sclerosis Journal ◽

10.1177/135245850000600604 ◽

2000 ◽

Vol 6 (6) ◽

pp. 382-385 ◽

Cited By ~ 28

Author(s):

Laura J Balcer ◽

Monika L Baier ◽

Amy M Kunkle ◽

Richard A Rudick ◽

Bianca Weinstock-Guttman ◽

...

Keyword(s):

Multiple Sclerosis ◽

Visual Function ◽

Reference Group ◽

Clinical Manifestations ◽

Phase Iii ◽

Eye Disease ◽

Visual Dysfunction ◽

Scale Scores ◽

Visual Function Questionnaire ◽

Composite Scores

Visual impairment is one of the most common clinical manifestations of Multiple Sclerosis (MS), and is strongly related to overall health-related quality of life (HRQOL) in MS and other disorders. However, the assessment of vision-specific HRQOL in patients with MS has been limited. The purpose of this study was to examine self-reported visual dysfunction in a clinically heterogeneous MS cohort using the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25). The VFQ-25 was administered by telephone interview to a subset of participants in a follow-up study to a phase III trial of interferon β-1a for relapsing-remitting MS. Mean VFQ-25 composite scores and selected sub-scale scores were significantly lower (worse) among patients in our MS cohort (n=35) compared with a published reference group of patients with no history of chronic eye disease (n=118). These differences were observed despite a relatively younger age and tighter distribution of binocular visual acuities in the MS cohort. Patients with MS in this study thus demonstrated a greater degree of self-reported visual dysfunction, as measured by the VFQ-25, compared with an eye disease-free reference group. The VFQ-25 is a potentially useful measure of vision-specific HRQOL in patients with MS.

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Orbital Fat Decompression for Thyroid Eye Disease

Ophthalmic Plastic and Reconstructive Surgery ◽

10.1097/iop.0000000000000260 ◽

2015 ◽

Vol 31 (3) ◽

pp. 215-218 ◽

Cited By ~ 26

Author(s):

Marta Calsina Prat ◽

Alexandra L. Braunstein ◽

Lora R. Dagi Glass ◽

Michael Kazim

Keyword(s):

Thyroid Eye Disease ◽

Eye Disease ◽

Orbital Fat

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Thyroid Eye Disease, Teprotumumab, and Hearing Loss: An Evolving Role for Otolaryngologists

Otolaryngology ◽

10.1177/01945998211004240 ◽

2021 ◽

pp. 019459982110042

Author(s):

Alexander Chern ◽

Lora R. Dagi Glass ◽

David A. Gudis

Keyword(s):

Hearing Loss ◽

Growth Factor ◽

Side Effects ◽

Human Monoclonal Antibody ◽

Multidisciplinary Treatment ◽

Thyroid Eye Disease ◽

Eye Disease ◽

Insulin Like Growth Factor ◽

Placebo Cohort ◽

Receptor Inhibitor

Teprotumumab is a human monoclonal antibody and IGF-1R (insulin-like growth factor 1 receptor) inhibitor approved for treatment of thyroid eye disease in adults. Recent clinical trials have demonstrated side effects, notably hearing loss, in the treatment cohort as compared with the placebo cohort. These unexpected otologic side effects may be understood through a mechanistic understanding of IGF-1 (insulin-like growth factor 1). As otolaryngologists who historically play a significant role in the multidisciplinary treatment of thyroid disease and its associated complications, we should be aware of and monitor the otologic side effects of teprotumumab. Clinicians who prescribe teprotumumab should strongly consider monitoring patients’ hearing with an audiologist and otolaryngologist.

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Teprotumumab for the treatment of chronic thyroid eye disease

Eye ◽

10.1038/s41433-021-01593-z ◽

2021 ◽

Author(s):

Shoaib Ugradar ◽

Julia Kang ◽

Andrea L. Kossler ◽

Erin Zimmerman ◽

Jenna Braun ◽

...

Keyword(s):

Volumetric Analysis ◽

Thyroid Eye Disease ◽

Eye Disease ◽

Soft Tissue Volume ◽

Before And After ◽

The Mean ◽

Clinically Significant ◽

Fat Volume ◽

Post Therapy ◽

Orbital Soft Tissue

Abstract Background Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of active Thyroid eye disease (TED). The current study reviews its efficacy in chronic TED. Methods In this retrospective review, consecutive patients with chronic stable TED (>2 years), who had received ≥3 infusions of teprotumumab were included. All patients had measurements of proptosis, and calculation of the CAS and diplopia scores before and after therapy. Five-point strabismus scores were also calculated. Patients who had imaging within 4 months prior to therapy and 6 weeks post therapy underwent orbital 3D volumetric analysis. Results Thirty-one patients met the inclusion criteria. The mean (SD) duration of TED was 81 months (56) and the mean (SD) number of infusions received by each patient was 7 (2). Mean (SD) reduction in proptosis for each study orbit was 3.5 mm (0.4) and 3 mm (0.3) for the fellow orbit. The CAS response was 90% for the study orbit and 87% for the fellow orbit. Of the 15 patients who had diplopia at baseline, 67% had a clinically significant response, while 47% had complete resolution following treatment. Following teprotumumab, mean (SD) reduction of muscle tissue was 2011 mm3 (1847) in the study orbit and 1620 mm3 (1759) in the fellow orbit. The mean (SD) reduction of fat volume was 2101 mm3 (1681) in the study orbit and 1370 mm3 (1181) in the fellow orbit. Conclusion Teprotumumab significantly reduces proptosis, inflammation, diplopia, strabismus and orbital soft tissue volume in patients with chronic TED.

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Orbital Fat Herniation Through the Superior Orbital Fissure in Thyroid Eye Disease

Ophthalmic Plastic and Reconstructive Surgery ◽

10.1097/iop.0000000000001768 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Author(s):

Karen M. Wai ◽

Natalie Wolkow ◽

Suzanne K. Freitag

Keyword(s):

Thyroid Eye Disease ◽

Eye Disease ◽

Superior Orbital Fissure ◽

Orbital Fat ◽

Fat Herniation

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Faculty Opinions recommendation of Orbital fat decompression for thyroid eye disease: retrospective case review and criteria for optimal case selection.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718765802.793507597 ◽

2015 ◽

Author(s):

Gene Howard

Keyword(s):

Thyroid Eye Disease ◽

Eye Disease ◽

Case Review ◽

Retrospective Case ◽

Orbital Fat ◽

Case Selection

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Guselkumab, an inhibitor of the IL-23p19 subunit, provides sustained improvement in signs and symptoms of active psoriatic arthritis: 1 year results of a phase III randomised study of patients who were biologic-naïve or TNFα inhibitor-experienced

RMD Open ◽

10.1136/rmdopen-2020-001457 ◽

2021 ◽

Vol 7 (1) ◽

pp. e001457

Author(s):

Christopher T Ritchlin ◽

Philip S Helliwell ◽

Wolf-Henning Boehncke ◽

Enrique R Soriano ◽

Elizabeth C Hsia ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Treated Patient ◽

Human Monoclonal Antibody ◽

Clinical Manifestations ◽

Study Participant ◽

Signs And Symptoms ◽

Phase Iii ◽

Sustained Improvement ◽

Randomised Study ◽

Tnfα Inhibitor

ObjectiveEvaluation of the efficacy and safety of guselkumab, a human monoclonal antibody targeting the interleukin-23p19 subunit, in patients with psoriatic arthritis (PsA) through 1 year.MethodsAdults who met ClASsification criteria for Psoriatic ARthritis, with active disease (≥3 swollen and ≥3 tender joints; C reactive protein ≥0.3 mg/dL) despite standard treatment (31% previously received ≤2 tumour necrosis factor inhibitors (TNFi)), were randomised (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week0, Week4, then Q8W; or placebo with cross-over to guselkumab 100 mg Q4W at Week24 (PBO→Q4W) through Week48. Clinical efficacy through Week52 (employing non-responder imputation) and adverse events (AEs) through Week60 were evaluated.ResultsOf 381 treated patients, 90% completed the study. Numerical increases in the proportions of patients achieving ≥20% improvement in ACR criteria (ACR20) were observed post-Week24, reaching 73% (94/128) and 60% (76/127) for Q4W-randomised and Q8W-randomised patients, respectively, by Week52. Proportions of patients achieving ACR50/ACR70/skin responses and minimal/very low disease activity were maintained, as were improvements in physical function and health-related quality of life, through Week52 in guselkumab-randomised patients. Response to guselkumab was maintained in both TNFi-naïve and TNFi-experienced patients. Serious AEs and serious infections occurred in similar proportions of guselkumab Q4W-randomised (3% and 0%) and Q8W-randomised (6% and 2%) patients through Week60, with no new safety concerns versus observations through Week24. No guselkumab-treated patient and two patients receiving placebo died; no study participant developed opportunistic infection or inflammatory bowel disease.ConclusionGuselkumab provided sustained improvement across multiple clinical manifestations of PsA, maintaining a favourable benefit-risk profile, through 1 year regardless of prior TNFi exposure.

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