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

Abstract

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.

Will biological agents supplant systemic glucocorticoids as the first-line treatment for thyroid-associated ophthalmopathy?

“…Efficacy in the fellow eye was similar to that in the study eye with regard to both proptosis and CAS improvement. The effects of teprotumumab appear to be durable as recent follow-up findings suggest that many responders experience sustained improvement, months following the treatment period (94). Thus, the results with teprotumumab are comparable to the best results thus far attained with surgical decompression (95).…”

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

“…This study was particularly significant, as this is the first medical therapy that has demonstrated a reduction in proptosis. Douglas determined that patients with higher baseline proptosis had a greater response to teprotumumab than patients with lower baseline proptosis (mean reduction 3.7 vs. 2.6 mm) [53]. Further, there was improvement in proptosis in all gender-and smoking-stratified groups.…”

“…Though IGF-1R is a widely expressed receptor, IGF-1R expression is increased on fibroblasts from the orbit, skin, and thyroid of patients with Graves' disease. The upregulation of IGF-1R and the TSHR in orbital fibroblasts has been proposed to lead to the accumulation of hyaluronan within orbital fat and muscle [10,53,54].…”

<p>Thyroid Eye Disease: How A Novel Therapy May Change The Treatment Paradigm</p>

“…Thyroid eye disease (TED) is a complex autoimmune disease characterized by orbital inflammation (active disease), with subsequent tissue remodeling and fibrosis when the disease becomes inactive 2,3. As TED progresses, it leads to proptosis, strabismus, corneal ulceration, and even optic neuropathy 2,4,5…”

“…Several treatment strategies are available, which focus on immune suppression 1. Though some provide short-term relief, they do not necessarily lead to disease course modification 2. The management of TED remains a major clinical and therapeutic challenge, as insufficient treatment can negatively impact patients’ quality of life (QoL) 2,6,7.…”