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      Rapid response of thyroid eye disease, peripheral edema, and acropathy to teprotumumab infusion

      case-report

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          Abstract

          Purpose

          We present a case of rapid improvement in symptoms of thyroid eye disease and amelioration of worsening peripheral edema and acropathy with infusion of teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor.

          Observations

          A 66 year old female with history of Hashimoto thyroiditis developed progressive thyroid eye disease (TED), peripheral edema, and acropathy attributable to acute Graves disease. Her signs and symptoms, refractory to oral steroid and diuretic therapy, rapidly improved following a standard dosing regimen of teprotumumab (one infusion 10 mg/kg then seven infusions 20 mg/kg) to resolution.

          Conclusions & importance

          Teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor, is the first medication approved by the FDA for use in TED. Teprotumumab may contribute to the treatment of extraocular manifestations of Graves disease, chief among these peripheral soft tissue manifestations.

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          Most cited references9

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          Graves' ophthalmopathy.

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            Teprotumumab, an insulin-like growth factor-1 receptor antagonist antibody, in the treatment of active thyroid eye disease: a focus on proptosis

            Thyroid eye disease is a disabling autoimmune disease associated with orbital inflammation and tissue remodeling which can result in significant proptosis, leading to visual alterations and is potentially sight threatening. Current evidence indicates that autoantibodies to the insulin-like growth factor 1 receptor (IGF-1R), along with the thyroid-stimulating hormone receptor (TSHR), mediate the pathogenesis in susceptible individuals. Teprotumumab, a monoclonal IGF-1R antagonist, has demonstrated previously in a 24 week, randomized, controlled trial to produce significant changes in composite outcomes of proptosis and clinical activity score as compared with placebo. Further examination of the proptosis results reported here, indicate that the proptosis outcome (≥ 2 mm reduction) was met in 71.4% of the teprotumumab-treated patients as compared with 20% of the placebo-treated patients (p < 0.001). Additionally, the proptosis benefit was observed early in the trial (study week 6), and all individual patients demonstrated some benefit at week 24. Improvement was noted among smokers, non-smokers, men and women, and particularly those with higher levels of proptosis at baseline. The level of proptosis reduction with teprotumumab reported here is similar to that seen with decompression surgery. If these results are confirmed in the ongoing Phase 3 trial, teprotumumab will offer an alternative to surgery and its associated complications.
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              Teprotumumab: Interpreting the Clinical Trials in the Context of Thyroid Eye Disease Pathogenesis and Current Therapies.

              Teprotumumab, a monoclonal antibody targeted against the insulin-like growth factor 1 (IGF-1) receptor, was recently approved by the United States Food and Drug Administration for the treatment of thyroid eye disease (TED). Phase 1 studies of teprotumumab for the treatment of malignancies demonstrated an acceptable safety profile but limited effectiveness. Basic research implicating the IGF-1 receptor on the CD-34+ orbital fibrocyte in the pathogenesis of TED renewed interest in the drug. Two multicenter, randomized, double-masked, clinical trials (phase 2 and 3) evaluated the efficacy of 8 infusions of teprotumumab every 3 weeks versus placebo in 170 patients with recent-onset active TED, as defined by a clinical activity score (CAS) of at least 4. Teprotumumab was superior to placebo for the primary efficacy end points in both studies: overall responder rate as defined by a reduction of 2 or more CAS points and a reduction of 2 mm or more in proptosis (69% vs. 20%; P < 0.001; phase 2 study) and proptosis responder rate as defined by a reduction of 2 mm or more in proptosis (83% vs. 10%; P < 0.001; phase 3 study). In both studies, treatment with teprotumumab compared with placebo achieved a significant mean reduction of proptosis (-3.0 mm vs. -0.3 mm, phase 2 study; -3.32 mm vs. -0.53 mm, phase 3 study) and CAS (-4.0 vs. -2.5, phase 2 study; -3.7 vs. -2.0, phase 3 study). Teprotumumab also resulted in a greater proportion of patients with a final CAS of 0 or 1, higher diplopia responder rate, and a larger improvement in the Graves' Ophthalmopathy Quality of Life overall score. More than half of patients (62%, phase 2 trial; 56%, phase 3 trial) who were primary end point responders maintained this response at 51 weeks after the last dose of therapy. The most common adverse events reported with teprotumumab included muscle spasms (25%), nausea (17%), alopecia (13%), diarrhea (13%), fatigue (10%), hearing impairment (10%), and hyperglycemia (8%). Teprotumumab is contraindicated for those with inflammatory bowel disease and who are pregnant. Although the current dosing regimen has proven effective for TED, dose-ranging studies including variable concentrations, infusion frequencies, and durations of teprotumumab therapy in the setting of TED have not been performed.
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                Author and article information

                Contributors
                Journal
                Am J Ophthalmol Case Rep
                Am J Ophthalmol Case Rep
                American Journal of Ophthalmology Case Reports
                Elsevier
                2451-9936
                02 March 2024
                June 2024
                02 March 2024
                : 34
                : 102031
                Affiliations
                [1]Rutgers New Jersey Medical School, Department of Ophthalmology & Visual Science, 90 Bergen St. Ste. 6100, Newark, NJ, 07103, USA
                Author notes
                [* ]Corresponding author. 90Bergen St. Ste. 6177, Newark, NJ, 07103, USA. turbinre@ 123456njms.rutgers.edu
                Article
                S2451-9936(24)00041-0 102031
                10.1016/j.ajoc.2024.102031
                10937103
                38487336
                f79a8da3-4837-4a61-8785-9ff0d1b00b6d
                © 2024 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 25 September 2023
                : 5 February 2024
                : 20 February 2024
                Categories
                Case Report

                thyroid eye disease,graves disease,thyroid dermopathy,peripheral edema,acropathy,teprotumumab

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