Teprotumumab for the Treatment of Thyroid Eye Disease: Why Should We Keep Our Eyes “Wide Open”?—A Clinical and Pharmacovigilance Point of View

<b>Objectives:</b> Thyroid eye disease (TED) treatment has been recently revolutionized with the approval of teprotumumab, a targeted insulin growth factor 1 receptor (IGF1R) inhibitor. To date, teprotumumab is the only FDA-approved drug for treating TED. In this article, we would like to temper the current enthusiasm around IGF1R inhibitors. <b>Methods:</b> critical review of the literature by independent academic practitioners. <b>Results:</b> several questions should be raised. First, "<i>how an orphan drug has become a blockbuster with annual sales exceeding $1 billion?</i>" Teprotumumab infusions are expensive, costing about USD 45,000 for one infusion and USD 360,000 for eight infusions in a 75 kg patient. Teprotumumab approval was based on two randomized clinical trials investigating active (clinical activity score ≥ 4) TED patients. Despite this, teprotumumab was approved by the FDA for "the treatment of TED" without distinguishing between active and inactive forms. The second question is as follows: "<i>how can a new drug, compared only to a placebo, become the new standard without being compared to historically established gold standard medical or surgical treatments?</i>" Teprotumumab has never been compared to other medical treatments in active TED nor to surgery in chronic TED. Up to 75% of patients may experience proptosis regression after treatment discontinuation. Finally, ototoxicity has emerged as a potentially devastating side effect requiring frequent monitoring. Investigation into the long-term side effects, especially in women of childbearing age, is also warranted. <b>Conclusions:</b> Teprotumumab is undoubtedly a major treatment option in TED. However, before prescribing a drug, practitioners should assess its benefit/risk ratio based on the following: (i) evidence-based medicine; (ii) their empirical experience; (iii) the cost/benefit analysis; (iv) the long-term outcomes and safety profile.