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Key points: Utilization of orbital decompressions (ODS) increased (CAGR: +3.2%) from 2000 to 2019.FDA approved teprotumumab in January 2020; ODS utilization decreased (CAGR: −14.9%) from 2019 to 2022.In 2022, total spending was substantially higher for teprotumumab ($325 million) than surgery ($580,000). [ABSTRACT FROM AUTHOR]

Background: Dry eye syndrome occurs in up to 85% of patients with thyroid eye disease (TED). Lacrimal gland enlargement correlates with subjective tearing and a reduction in quality of life in patients with TED. Methods: In this prospective longitudinal study, patients presenting for the treatment of TED were considered for eligible. Primary outcomes included a change in the volume of the lacrimal gland and the production of tears following treatment with teprotumumab. The volume of lacrimal glands and proptosis was calculated using 3D volumetric analysis. Tear production was measured by Schirmer's test and associated symptoms were assessed using the VLSQ‐8. The orbit with the most proptosis was designated the study orbit and the contralateral orbit was designated the fellow orbit. Results: Twenty patients were included. Mean (SD) age was 61 (18) and mean duration of TED prior to therapy was 48 months (47). Lacrimal gland volume in the study orbit decreased from 768 mm3 (288) to 486 mm3 (173) (p < 0.01) following therapy. For the fellow orbit, volume reduced from 637 mm3 (261) to 379 mm3 (147) (p < 0.01). Schirmer's test reading (STR) in the study orbit increased from 14.5 mm (8.2) to 23 mm (10) (p < 0.01) (59%) following treatment. In the fellow orbit, STR increased from 12.7 mm (7) to 21 mm (9) post therapy (69%) (p < 0.01). There was a significant improvement on all parts of the VLSQ‐8. Conclusion: Teprotumumab significantly reduces TED related expansion of the lacrimal gland, increases tear production, and improves dry eye symptoms. [ABSTRACT FROM AUTHOR]

Objective: To assess a series of patients receiving teprotumumab therapy and objectively quantify the rates of otologic adverse events. Study Design: A prospective cohort study of adult patients receiving teprotumumab between May 2020 and January 2022. Setting: Tertiary referral center. Methods: Prior to treatment initiation, an ototoxicity‐specific audiometric battery was completed, which included conventional audiometry (frequencies 250‐8000 Hz), ultrahigh‐frequency audiometry (9000‐20,000 Hz), tympanometry, speech discrimination scores, and distortion product otoacoustic emissions (DPOAEs). Testing was then repeated after treatment completion. Results: In total, 35 patients were recruited, with a median (range) age of 48.5 years (21‐74), and 8 (22.8%) were male. The most common subjective symptom reported was a hearing decline (25.7%), followed by aural fullness (17.1%) and tinnitus (14.3%). Fourteen patients had both pre‐ and posttreatment audiometric data. Among them, 3 patients (21.4%) were found to have changes in standard frequency audiometry, and 10 (71.4%) had changes in high‐frequency audiometry, with 2 patients having changes in both. Less than half (n = 5) of the 11 patients with changes in standard or high‐frequency pure tone hearing noted subjective hearing decline. Changes in DPOAE were noted in 4 patients out of 13 (30.7%). Two patients discontinued treatment due to hearing decline. Finally, 3 patients (8.6%) were diagnosed with patulous eustachian tube (PET) by an otolaryngologist, and another 3 patients are suspected to have PET based on symptom description during ophthalmologic follow‐up. Conclusion: In our cohort, a high incidence of otologic symptoms was found to be associated with teprotumumab usage. Subjective hearing decline, changes in ultrahigh‐frequency hearing as well as eustachian tube dysfunction may be encountered and suggest the potential ototoxicity of teprotumumab. [ABSTRACT FROM AUTHOR]

We report a 51‐year‐old woman with thyroid eye disease and biopsy‐proven pretibial myxedema that was subsequently treated with teprotumumab with improvement. [ABSTRACT FROM AUTHOR]

Graves' orbitopathy (GO) is an orbital autoimmune disorder and the main extrathyroidal manifestation of Graves' disease, the most common cause of hyperthyroidism. GO affects about 30% of Graves' patients, although fewer than 10% have severe forms requiring immunosuppressive treatments. Management of GO requires a multidisciplinary approach. Medical therapies for active moderate‐to‐severe forms of GO (traditionally, high‐dose glucocorticoids) often provide unsatisfactory results, and subsequently surgeries are often needed to cure residual manifestations. The aim of this review is to provide an updated overview of current concepts regarding the epidemiology, pathogenesis, assessment, and treatment of GO, and to present emerging targeted therapies and therapeutic perspectives. Original articles, clinical trials, systematic reviews, and meta‐analyses from 1980 to 2021 were searched using the following terms: Graves' disease, Graves' orbitopathy, thyroid eye disease, glucocorticoids, orbital radiotherapy, rituximab, cyclosporine, azathioprine, teprotumumab, TSH‐receptor antibody, smoking, hyperthyroidism, hypothyroidism, thyroidectomy, radioactive iodine, and antithyroid drugs. Recent studies suggest a secular trend toward a milder phenotype of GO. Standardized assessment at a thyroid eye clinic allows for a better general management plan. Treatment of active moderate‐to‐severe forms of GO still relies in most cases on high‐dose systemic—mainly intravenous—glucocorticoids as monotherapy or in combination with other therapies—such as mycophenolate, cyclosporine, azathioprine, or orbital radiotherapy—but novel biological agents—including teprotumumab, rituximab, and tocilizumab—have achieved encouraging results. [ABSTRACT FROM AUTHOR]

To compare the effects of different treatment modalities on active, moderate‐to‐severe Graves' orbitopathy (GO). We searched PubMed and Embase for randomized controlled trials published up to 30 Nov 2020, of different modalities for the treatment of active, moderate‐to‐severe GO. We performed Bayesian network meta‐analyses. This study is registered with PROSPERO (CRD42020166287). Fifteen RCTs were identified. Network meta‐analysis showed that in comparison with placebo, teprotumumab, mycophenolate plus intravenous glucocorticoids (IVGCs), mycophenolate, rituximab, azathioprine, IVGCs, orbital radiotherapy, oral glucocorticoids (OGCs) were effective treatments (ordered from most effective to least effective). Teprotumumab was more efficacious in reducing proptosis than IVGCs. No significant difference in changes in diplopia grade was recorded between teprotumumab, rituximab, orbital radiotherapy and IVGCs. Low (4.5–5 g), middle (6 g) and high (7–8 g) cumulative doses of IVGCs were shown to be more effective than OGC in improving the overall response rate, but the very low‐group (<3 g) seemed to have a lower risk of adverse events. We found that teprotumumab offered the highest level of efficacy in terms of the overall response rate and was more efficacious in reducing proptosis than IVGCs. With regard to different dosages of IVGCs, the cumulative dose of 4.5–5 g of IVGCs seems to be the most appropriate schedule in terms of efficacy and safety outcomes. Due to the limited number of patients treated with teprotumumab and the lack of comparison with other effective therapeutics, teprotumumab might not become the standard first‐line therapy for active, moderate‐to‐severe GO. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]