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Nova chance para a cura da oftalmopatia de Graves: Teprotumumabe


Artigo publicado nesta semana no NEJM relata a experiência altamente positiva com um novo agente biológico para tratamento da oftalmopatia associada a casos mais severos de hipertireoidismo autoimune.

A inibição do receptor do fator de cescimento similar à insulina (IGF-1R) resultou em melhora detectável dos olhos em 69% dos 88 pacientes estudados, contra 20% no grupo placebo. Para-efeitos ocorreram apenas em diabéticos, com descontrole leve da glicemia.

O Abstract você pode ler no seguimento.

Teprotumumab for Thyroid-Associated Ophthalmopathy

Terry J. Smith, M.D., George J. Kahaly, M.D., Ph.D., Daniel G. Ezra, M.D., James C. Fleming, M.D., Roger A. Dailey, M.D., Rosa A. Tang, M.D., Gerald J. Harris, M.D., Alessandro Antonelli, M.D., Mario Salvi, M.D., Robert A. Goldberg, M.D., James W. Gigantelli, M.D., Steven M. Couch, M.D., Erin M. Shriver, M.D., Brent R. Hayek, M.D., Eric M. Hink, M.D., Richard M. Woodward, Ph.D., Kathleen Gabriel, R.N., Guido Magni, M.D., Ph.D., and Raymond S. Douglas, M.D., Ph.D.
N Engl J Med 2017; 376:1748-1761

BACKGROUND
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 =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 (P<0.001). 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 (P<0.001). 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.