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  • Teprotumumab Effective for Thyroid-Associated Ophthalmopathy

    By Lynda Seminara and selected by Deepak P. Edward, MD
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    Journal Highlights

    The New England Journal of Medicine
    2017;376(18):1748-1761

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    The pathogenesis of thyroid-associated ophthalmopathy, which is commonly associated with Graves disease, is poorly understood, and current treatments are inconsistently effective and potentially unsafe. Smith et al. investigated wheth­er teprotumumab was effective at treat­ing active ophthalmopathy. They found that the drug, a human monoclonal antibody that inhibits insulin-like growth factor I receptor (IGF-IR), was more effective than placebo in reducing proptosis and Clinical Activity Score (CAS).

    This double-masked, 3-phase multicenter trial involved 87 patients (age range, 18-75 years) with ophthalmop­athy who were diagnosed within 9 months after symptom onset and had a CAS tally of ≥ 4 points (out of 7) in the study eye. During the 24-week inter­vention phase, patients were assigned randomly to receive either 8 intravenous infusions of teprotumumab (n = 42) or placebo (n = 45), with 1 infusion de­livered at baseline (10 mg/kg) and the others (20 mg/kg) delivered at 3-week intervals. The primary outcome was response in the study eye, defined as a decrease of ≥ 2 points in CAS and ≥ 2 mm in proptosis by week 24. Second­ary outcomes included proptosis and CAS results (i.e., continuous variables). Adverse events (AEs) were evaluated as safety endpoints.

    By week 24, 29 of 42 teprotumum­ab recipients (69%) demonstrated a response, versus 9 of 45 patients (20%) in the placebo group. Onset of response occurred earlier in the teprotumumab group, with 18 of 42 patients (43%) responding by week 6, versus 2 of 45 patients (4%) in the placebo group. Be­tween-group differences increased with time. Most AEs were mild and resolved without treatment. Hyperglycemia, the only drug-related AE, was controlled with medication adjustments.

    Although 1-year follow-up is ongoing, the authors concluded that 24-week teprotumumab therapy is clinically beneficial for active mod­erate-to-severe thyroid-associated ophthalmopathy. The comprehensive effects suggest that the therapeutic mechanism is upstream from the or­bital inflammation. The U.S. Food and Drug Administration has since desig­nated teprotumumab a breakthrough therapy.

    The original article can be found here.