ePortfolio #1

Teprotumumab

(Tepezza®)

Teprotumumab, marketed as Tepezza® is a monoclonal antibody developed for the treatment of an autoimmune disorder resulting in Thyroid eye disease (TED).  Individuals with TED often experience symptoms ranging from mild to severe, including dry eyes, orbital pain, irritation, and eyelid retraction, proptosis/exophthalmos (protrusion/bulging of eyes from orbital socket), diplopia (double vision), and strabismus (abnormal alignment of the eye) (1).  Past treatments included glucocorticoid steroids, orbital radiation, and orbital decompression surgery, reducing discomfort but not addressing the autoimmune condition.  Tepezza®, manufactured by Horizon Therapeutics plc, was discovered and approved by the United States Food and Drug Administration (USFDA) in 2020.  Teprotumumab is administered through intravenous infusion at a dosage of 10mg/kg of body mass for the first infusion and 20mg/kg for 7 additional infusions at 3-week intervals totaling 24 weeks(2).  Severe side effects include loss of hearing and considerations should be taken for individuals with hyperglycemia, diabetes, and/or irritable bowel syndrome (IBS).

In TED there is a failure for the body to properly regulate thyroid stimulating hormone receptor (TSH-R) and insulin like growth factor 1 receptor (IGF-1R) complex antibody signaling in orbital fibroblasts.   When IGF-1R is overexpressed autoantibodies are signaled to the area, resulting in cytokine production that leads to inflammation of cells and tissues located around the eye (3).  Teprotumumab is an IgG1 antibody that works by blocking autoantibodies from binding to IGF-1R (4).  This action is thought to reduce the inflammatory response mediated by IGF-1R.  In a study conducted by Horizon Therapeutics, results published seem to indicate that after 24 weeks of a positive correlation in the reduction of symptoms could be observed and shows promise for future long-range treatment of TED (5).

References

  1. Slentz, D. H., Nelson, C. C., & Smith, T. J. (2020). Teprotumumab: a novel therapeutic monoclonal antibody for thyroid-associated ophthalmopathy. Expert opinion on investigational drugs, 29(7), 645–649. https://doi.org/10.1080/13543784.2020.1772752
  2. Yvon, C., Khong, J. J., Malhotra, R. et al. (2023). Teprotumumab. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. https://www.ncbi.nlm.nih.gov/books/NBK585036/
  3. Douglas, R. S. MD, PhD, Wang, Y. MD, Dailey, R. A. MD, Harris, G. J. MD, Wester, S. T. MD, Schiffman, J. S. MD, Tang, R. A. MD, Fowler, B. MD, Fleming, J. MD, Smith, T. J. MD. (2021). Teprotumumab in Clinical Practice: Recommendations and Considerations From the OPTIC Trial Investigators. Journal of Neuro-Ophthalmology 41(4):p 461-468.| DOI: 10.1097/WNO.0000000000001134. https://journals.lww.com/jneuro-ophthalmology/fulltext/2021/12000/teprotumumab_in_clinical_practice__recommendations.6.aspx
  4. Ugradar, S., Kang, J., Kossler, A. L. et al. (2022).  Teprotumumab for the treatment of chronic thyroid eye disease. Eye 36, 1553–1559. https://doi.org/10.1038/s41433-021-01593-z
  5. Couch S. M. (2022). Teprotumumab (Tepezza) for Thyroid Eye Disease. Missouri medicine, 119(1), 36–41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312457/