Teprotumumab bij een actieve oogziekte van Graves

De behandeling van de oogziekte blijft moeizaam en lastig. De oogziekte komt voor bij de ziekte van Graves en Hashimoto. Huidige behandelingen, die voornamelijk bestaan uit prednison, hebben een beperkte werkzaamheid maar wel veel bijwerkingen. Met teprotumumab kan mogelijk de insuline-achtige groeifactor I receptor (IGF-IR) geremd worden. Dat zou een nieuwe aanpak zijn om het onderliggende auto-immuun ziekteverloop van de oogziekte te verzwakken.

Teprotumumab for thyroid-associated ophthalmopathy
Terry J. Smith en anderen
N Engl J Med 2017; 376:1748-1761 May 4, 2017DOI: 10.1056/NEJMoa1614949

Teprotumumab treatment in patients with active thyroid eye disease
ClinicalTrials.gov number, NCT01868997

Thyroid-associated ophthalmopathy, a condition commonly associated with Graves’ disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy.

Methods

We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of more than 3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves’ ophthalmopathy–specific quality-of-life questionnaire. Adverse events were assessed.

Results

In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24. Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response. Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes.

Conclusions

In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997.)