RESUMO
BACKGROUND: Teprotumumab, a novel IGF-1R antibody, has been shown to significantly reduce the signs of acute and chronic Thyroid Eye Disease (TED). Light sensitivity is a reported symptom in patients with TED. There is a lack of a prospective study that has explored the effects on light sensitivity in a large cohort of patients with acute and chronic TED following treatment with teprotumumab. METHODS: Consecutive patients who were diagnosed with TED and reported light sensitivity at baseline were considered for study eligibility. All patients had measurements of Visual Light Sensitivity Questionnaire-8 (VLSQ-8), proptosis, clinical activity score (CAS), and MRD1 (distance between the upper eyelid margin and corneal reflex, mm) and MRD2 (distance between the lower eyelid margin and corneal reflex, mm) before and after treatment. RESULTS: Ninety patients (41 acute, 49 chronic) met the inclusion criteria. The mean (SD) age was 47.3 (14.3). Eighty-six (95.6%) patients completed all 8 infusions. There was a significant reduction in the total score and across all categories of the VLSQ-8 (p < 0.01 for all). Seventy-two (80%) patients had a clinically significant improvement (≥2 reduction) in at least one category. There was no significant difference in the total VLSQ-8 score between the acute and chronic group (p = 0.8). CONCLUSION: Teprotumumab improves light sensitivity in patients with acute and chronic TED. The results of this study highlight that the improvements in light sensitivity following treatment are not directly related to the mechanical changes in TED, suggesting another underlying mechanism is potentially involved.
RESUMO
BACKGROUND: Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of acute and chronic thyroid eye disease (TED) related to hyperthyroidism. Given the lower incidence of TED associated with hypothyroidism / euthyroidism, there is a paucity of data regarding the efficacy of teprotumumab in this group. METHODS: In this multicenter study, consecutive patients who had been diagnosed with TED, presenting with either hypothyroidism or euthyroidism as their baseline thyroid dysfunction and treated with teprotumumab were included. All patients had measurements of proptosis, clinical activity scores (CAS), diplopia scores and four-point strabismus scores before and after therapy. RESULTS: Twenty-six patients met the inclusion criteria. Mean age was 48 ± 14 years old and mean duration of TED prior to treatment was 31 ± 43 months. All patients received 8 infusions. Mean (SD) reduction in proptosis for study orbits was 2.7 mm (1.8) (p < 0.05) and 1.8 mm (2.0) for the fellow orbit (p < 0.05). In the study orbit, mean (SD) CAS was 2.3 (1.3) before therapy and 1.0 (1.0) following therapy (p < 0.05). At baseline, mean (SD) diplopia score was 1.2 (1.1) and 0.9 (1.1) following therapy (p < 0.05). CONCLUSION: Teprotumumab reduces proptosis and inflammation in patients presenting with TED associated with hypothyroidism and euthyroidism. The results of this study highlight the potential for teprotumumab therapy in this subgroup and also provide a unique insight into the potential role of the IGF-1R in these patients.
RESUMO
Thyroid eye disease (TED) is the most common extra thyroidal manifestation of Graves' disease (GD). It may also present in those who are hypothyroid or euthyroid. The characteristic clinical manifestations of TED: chemosis, lid swelling, proptosis and diplopia are driven by a combination of inflammation and extracellular matrix modification. It has recently emerged that one of the major drivers of this molecular signature is the over-expression of the insulin like growth factor-1 receptor (IGF-1R) on key effector cells in TED pathogenesis. The overexpression of the IGF-1R is coupled with a dysregulation of the IGF-1R axis, which links other pathways that modulate inflammation, such as fibrosis and extracellular matrix organization, in patients with TED. This overexpression is also found to persist from the acute stage into the chronic phase. Teprotumumab, a fully human immunoglobulin (Ig) G1 monoclonal antibody that inhibits the IGF-1R, recently gained approval in the US for the treatment of TED. In phase 2 and phase 3 clinical studies, teprotumumab showed efficacy in reducing inflammation, proptosis, diplopia and burden on quality of life, in patients who were treated. Post introduction studies have confirmed the results of the phase 2 and phase 3 studies. Since 2020, over 5, 800 patients have been treated with teprotumumab and it appears to be well tolerated. The American Thyroid Association and the European Thyroid Association have recommended it as first line therapy for patients with moderate to severe TED, who display features of proptosis and diplopia.