A New Era in the Treatment of Thyroid Eye Disease

Abstract

Improved understanding of thyroid eye disease (TED) pathogenesis has facilitated identification of a targeted molecular approach for TED treatment offering the potential to halt or slow disease progression in a nonsurgical manner. Herein, we provide a summary of the current knowledge of TED management, followed by discussion of a novel insulin-like growth factor-1 receptor (IGF-1R) antagonist antibody and its potential to change the course of the disease.DESIGN: Perspective. METHODS: Review of the literature and authors' experience.RESULTS: Many publications demonstrate IGF-1R overexpression in TED, and its activation as an autoantigen as a critical factor in TED pathogenesis. Several in vitro studies demonstrate that IGF-1R inhibition attenuates downstream molecular events including cytokine and hyaluronan production, and cellular differentiation. These observations led to the hypothesis that blocking IGF-1R may abrogate the clinical progression of TED. The recent completion of phase 2 and 3 randomized, placebo-controlled trials demonstrate the efficacy and safety of teprotumumab, a fully human monoclonal IGF-1R antagonist antibody, in patients with moderate-to-severe, active TED. Both the phase 2 and the recent phase 3 study results demonstrate that more patients with active TED receiving teprotumumab experienced a meaningful improvement in proptosis.CONCLUSIONS: Current TED treatment strategies target inflammation and symptoms, but do not modify the disease course. Therefore, proptosis as well as strabismus and its resulting diplopia often remain, impacting patient well-being and quality of life over the long term. Targeted molecular therapy using teprotumumab demonstrates disease-modifying benefits with the potential to shift the paradigm for TED treatment. (Am J

Current Understanding of the Progression and Management of Thyroid Associated Orbitopathy: A Systematic Review

“…There was a significant difference in proptosis reduction between the teprotumumab group and the placebo group at weeks 6, 12, 18, and 24. Data from secondary endpoints are yet to be presented at the time of this review [56,57].…”

Medical management of thyroid eye disease – A paradigm shift

“…A landmark breakthrough is the introduction of specific IGF-1R blocker teprotumumab. [ 6 22 23 ] It has been demonstrated that eight infusions of teprotumumab over 24 weeks were associated with clinical improvement in patients with moderate-to-severe, active TED, shown by reductions in CAS, proptosis, subjective diplopia, and improved quality of life. [ 22 ] The reduction in proptosis was comparable to orbital decompression.…”

“…The biphasic natural history of TED as described over six decades ago by Francis Rundle[ 6 7 ] has an initial active, inflammatory, progressive component, followed by a static, noninflammatory, fibrotic sequelae. [ 8 9 ] The clinical course, however, is heterogenous with numerous permutations of severity and duration of inflammation and functional derangement.…”

Anaesthesia for ophthalmic procedures in patients with thyroid eye disease

“…3,10,14 However, no treatments have been shown to prevent or reverse the underlying tissue changes in TED. 15 When surgery is indicated, orbital decompression is typically performed first, then strabismus surgery and eyelid retraction considered last, as each preceding procedure may influence the appearance and outcome of the following operation. 16,17 Thyroid diseases have several implications for anaesthetists.…”