• Oculoplastics/Orbit

    In this multicenter randomized trial, teprotumumab was more effective than placebo in reducing clinical activity and proptosis in patients with active thyroid-associated ophthalmopathy.

    A drug originally developed as a cancer therapy, teprotumumab is a fully human monoclonal antibody that inhibits the insulin-like growth factor 1 (IGF-1) receptor.

    "This treatment represents an unheralded advance and is the result of more than 20 years of research," said Raymond S. Douglas, MD, PhD, the study's senior author and professor of ophthalmology and visual sciences at the University of Michigan.

    Study design

    The multicenter, double-masked, randomized, placebo-controlled trial included 45 patients in the placebo group and 42 in the teprotumumab (River Vision Development) group. Medication or placebo was administered intravenously to patients with active, moderate to severe thyroid-associated ophthalmopathy every 3 weeks for a total of 24 weeks. Response was defined as a reduction of 2 or more points in the Clinical Activity Score and a reduction of 2 mm or more in proptosis.


    Therapeutic effects were rapid and evident by 6 weeks: 43% of the teprotumumab group had a response, compared with just 4% in controls (P<0.001). By 24 weeks, 69% of teprotumumab patients had responded to treatment, more than 3-fold higher than the control group (20%, P<0.001). The only drug-related adverse event was hyperglycemia in patients with diabetes, which was successfully controlled by adjustment in diabetes medication.


    Although the study does reach a statistically significant difference, the number of subjects is low given the incidence of thyroid eye disease. The 2 populations of patients are relatively well matched; however, this is not a homogenous disease, and there are subtle differences between treatment groups such as smoking status and time since initiation of treatment for thyroid disease.

    Clinical significance

    At this time, successful treatment of active thyroid eye disease has been reported with orbital radiation, intravenous methylprednisolone and the biologic agents rituximab, etanercept, adalimumab, toclizumab and teprotumumab. A randomized, prospective, case-controlled study comparing each of the above treatments along with a placebo group in treating active thyroid eye disease would be useful to evaluate which agent is most effective. In addition, side effects and the cost of each therapy should be considered.