Teprotumumab is a novel biologic agent that has proven efficacy in patients with thyroid eye disease (TED) and potential for compressive optic neuropathy, but adverse events have been noted with its use.
Study design
Teprotumumab, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, was approved by the US FDA in 2020 for the treatment of TED. The authors conducted a systematic review of the published literature regarding the mechanism of action of teprotumumab and its use on patients with TED.
Outcomes
In TED, orbital fibroblasts overexpress IGF-1R, leading to the release of inflammatory cytokines and increased production of hyaluronan. This mechanism is the main contributing factor for the significant enlargement of fat and muscle within the orbit. Teprotumumab blocks the signaling that upregulates proinflammatory cytokines and hyaluronan release. In patients with TED, teprotumumab has been shown to improve proptosis and diplopia, and to reduce inflammation by reversing the enlargement of soft tissues in acute and chronic stages. This improvement can be rapid (within weeks) and may have a long-lasting effect. Some evidence also suggests that teprotumumab may have a role in improving compressive optic neuropathy related to TED. However, adverse effects seen with teprotumumab use include hearing loss, hyperglycemia, and muscle spasm.
Limitations
Teprotumumab is not approved for use in pregnant or lactating women. While this review includes case series and case reports suggesting that teprotumumab might be beneficial in compressive optic neuropathy, further studies are needed to solidify teprotumumab's efficacy for this condition.
Clinical significance
The introduction of teprotumumab in TED is an exciting and revolutionary intervention, as it is the only medication that reduces the fat and muscle expansion within the orbit. It has proved its efficacy in reducing proptosis, diplopia, and inflammation in patients with TED, although many patients remain non-responders to treatment. Studies have yet to define the optimal duration of maintenance therapy with TED, the role of re-treatment, or the effect of teprotumumab on recovery if a patient were to require a reconstructive surgical intervention. Although teprotumumab is fairly safe when under supervision, serious adverse effects have been reported. Hence, careful patient selection and monitoring are imperative for successful treatment and reduction of complications. Teprotumumab is expensive, and obtaining insurance authorization can be time-consuming and challenging. It should be prescribed in conjunction with care by a multidisciplinary team, including a primary care physician, an oculoplastic surgeon, and an endocrinologist.