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Teprotumumab for Thyroid-Associated Ophthalmopathy.

Abstract 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.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title the new england journal of medicine
Publication Year Start




PMID- 28467880
OWN - NLM
STAT- MEDLINE
DA  - 20170503
DCOM- 20170512
LR  - 20170512
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 376
IP  - 18
DP  - 2017 May 04
TI  - Teprotumumab for Thyroid-Associated Ophthalmopathy.
PG  - 1748-1761
LID - 10.1056/NEJMoa1614949 [doi]
AB  - 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. (Funded by River Vision
      Development and others; ClinicalTrials.gov number, NCT01868997 .).
FAU - Smith, Terry J
AU  - Smith TJ
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Kahaly, George J
AU  - Kahaly GJ
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Ezra, Daniel G
AU  - Ezra DG
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Fleming, James C
AU  - Fleming JC
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Dailey, Roger A
AU  - Dailey RA
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Tang, Rosa A
AU  - Tang RA
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Harris, Gerald J
AU  - Harris GJ
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Antonelli, Alessandro
AU  - Antonelli A
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Salvi, Mario
AU  - Salvi M
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Goldberg, Robert A
AU  - Goldberg RA
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Gigantelli, James W
AU  - Gigantelli JW
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Couch, Steven M
AU  - Couch SM
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Shriver, Erin M
AU  - Shriver EM
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Hayek, Brent R
AU  - Hayek BR
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Hink, Eric M
AU  - Hink EM
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Woodward, Richard M
AU  - Woodward RM
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Gabriel, Kathleen
AU  - Gabriel K
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Magni, Guido
AU  - Magni G
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
FAU - Douglas, Raymond S
AU  - Douglas RS
AD  - From the Department of Ophthalmology and Visual Sciences, Kellogg Eye Center
      (T.J.S., R.S.D.), and the Division of Metabolism, Endocrinology, and Diabetes,
      Department of Internal Medicine (T.J.S.), University of Michigan Medical School, 
      Ann Arbor; the Department of Medicine, Johannes Gutenberg University Medical
      Center, Mainz, Germany (G.J.K.); Moorfields Eye Hospital, London (D.G.E.); the
      University of Tennessee Health Science Center, Memphis (J.C.F.); the Oculofacial 
      Plastic Surgery Division, Oregon Health and Science University, Portland
      (R.A.D.); Eye Wellness Center, Neuro-Ophthalmology of Texas, Houston (R.A.T.);
      the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee
      (G.J.H.); the Department of Clinical and Experimental Medicine, University of
      Pisa, Pisa (A.A.), and the Endocrinology and Diabetology Unit, Fondazione IRCCS
      Ca' Granda, University of Milan, Milan (M.S.) - both in Italy; the Jules Stein
      Eye Institute, University of California, Los Angeles, Los Angeles (R.A.G.); the
      University of Nebraska Medical Center, Omaha (J.W.G.); Barnes-Jewish Hospital,
      Washington University, St. Louis (S.M.C.); the Department of Ophthalmology,
      University of Iowa Hospitals and Clinics, Iowa City (E.M.S.); the Department of
      Ophthalmology, Emory University, Atlanta (B.R.H.); the Department of
      Ophthalmology, University of Colorado, Aurora (E.M.H.); and River Vision
      Development, New York (R.M.W., K.G., G.M.).
LA  - eng
SI  - ClinicalTrials.gov/NCT01868997
GR  - R01 FD004792/FD/FDA HHS/United States
GR  - R01 EY008976/EY/NEI NIH HHS/United States
GR  - R01 EY011708/EY/NEI NIH HHS/United States
GR  - R01 DK063121/DK/NIDDK NIH HHS/United States
GR  - UM1 AI110557/AI/NIAID NIH HHS/United States
GR  - F31 EY007003/EY/NEI NIH HHS/United States
GR  - R01 EY021197/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Immunologic Factors)
RN  - 0 (R-1507 monoclonal antibody)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - AIM
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/adverse effects/*therapeutic use
MH  - Diabetes Complications
MH  - Double-Blind Method
MH  - Exophthalmos/drug therapy
MH  - Female
MH  - Graves Ophthalmopathy/complications/*drug therapy
MH  - Humans
MH  - Hyperglycemia/chemically induced
MH  - Immunologic Factors/adverse effects/*therapeutic use
MH  - Insulin-Like Growth Factor I/*antagonists & inhibitors
MH  - Intention to Treat Analysis
MH  - Logistic Models
MH  - Male
MH  - Middle Aged
MH  - Quality of Life
EDAT- 2017/05/04 06:00
MHDA- 2017/05/13 06:00
CRDT- 2017/05/04 06:00
AID - 10.1056/NEJMoa1614949 [doi]
PST - ppublish
SO  - N Engl J Med. 2017 May 4;376(18):1748-1761. doi: 10.1056/NEJMoa1614949.

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