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Tytuł:
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Ozanimod Induction and Maintenance Treatment for Ulcerative Colitis.
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Autorzy:
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Sandborn WJ; From the University of California, San Diego, La Jolla (W.J.S.), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) - both in California; Robarts Clinical Trials, Robarts Research Institute, and the Department of Medicine, Western University, London, ON (B.G.F.), and the University of Calgary, Calgary, AB (S. Ghosh) - all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V.); and Northwestern University, Evanston, IL (S.B.H.).
Feagan BG; From the University of California, San Diego, La Jolla (W.J.S.), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) - both in California; Robarts Clinical Trials, Robarts Research Institute, and the Department of Medicine, Western University, London, ON (B.G.F.), and the University of Calgary, Calgary, AB (S. Ghosh) - all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V.); and Northwestern University, Evanston, IL (S.B.H.).
Wolf DC; From the University of California, San Diego, La Jolla (W.J.S.), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) - both in California; Robarts Clinical Trials, Robarts Research Institute, and the Department of Medicine, Western University, London, ON (B.G.F.), and the University of Calgary, Calgary, AB (S. Ghosh) - all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V.); and Northwestern University, Evanston, IL (S.B.H.).
D'Haens G; From the University of California, San Diego, La Jolla (W.J.S.), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) - both in California; Robarts Clinical Trials, Robarts Research Institute, and the Department of Medicine, Western University, London, ON (B.G.F.), and the University of Calgary, Calgary, AB (S. Ghosh) - all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V.); and Northwestern University, Evanston, IL (S.B.H.).
Vermeire S; From the University of California, San Diego, La Jolla (W.J.S.), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) - both in California; Robarts Clinical Trials, Robarts Research Institute, and the Department of Medicine, Western University, London, ON (B.G.F.), and the University of Calgary, Calgary, AB (S. Ghosh) - all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V.); and Northwestern University, Evanston, IL (S.B.H.).
Hanauer SB; From the University of California, San Diego, La Jolla (W.J.S.), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) - both in California; Robarts Clinical Trials, Robarts Research Institute, and the Department of Medicine, Western University, London, ON (B.G.F.), and the University of Calgary, Calgary, AB (S. Ghosh) - all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V.); and Northwestern University, Evanston, IL (S.B.H.).
Ghosh S; From the University of California, San Diego, La Jolla (W.J.S.), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) - both in California; Robarts Clinical Trials, Robarts Research Institute, and the Department of Medicine, Western University, London, ON (B.G.F.), and the University of Calgary, Calgary, AB (S. Ghosh) - all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V.); and Northwestern University, Evanston, IL (S.B.H.).
Smith H; From the University of California, San Diego, La Jolla (W.J.S.), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) - both in California; Robarts Clinical Trials, Robarts Research Institute, and the Department of Medicine, Western University, London, ON (B.G.F.), and the University of Calgary, Calgary, AB (S. Ghosh) - all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V.); and Northwestern University, Evanston, IL (S.B.H.).
Cravets M; From the University of California, San Diego, La Jolla (W.J.S.), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) - both in California; Robarts Clinical Trials, Robarts Research Institute, and the Department of Medicine, Western University, London, ON (B.G.F.), and the University of Calgary, Calgary, AB (S. Ghosh) - all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V.); and Northwestern University, Evanston, IL (S.B.H.).
Frohna PA; From the University of California, San Diego, La Jolla (W.J.S.), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) - both in California; Robarts Clinical Trials, Robarts Research Institute, and the Department of Medicine, Western University, London, ON (B.G.F.), and the University of Calgary, Calgary, AB (S. Ghosh) - all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V.); and Northwestern University, Evanston, IL (S.B.H.).
Aranda R; From the University of California, San Diego, La Jolla (W.J.S.), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) - both in California; Robarts Clinical Trials, Robarts Research Institute, and the Department of Medicine, Western University, London, ON (B.G.F.), and the University of Calgary, Calgary, AB (S. Ghosh) - all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V.); and Northwestern University, Evanston, IL (S.B.H.).
Gujrathi S; From the University of California, San Diego, La Jolla (W.J.S.), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) - both in California; Robarts Clinical Trials, Robarts Research Institute, and the Department of Medicine, Western University, London, ON (B.G.F.), and the University of Calgary, Calgary, AB (S. Ghosh) - all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V.); and Northwestern University, Evanston, IL (S.B.H.).
Olson A; From the University of California, San Diego, La Jolla (W.J.S.), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) - both in California; Robarts Clinical Trials, Robarts Research Institute, and the Department of Medicine, Western University, London, ON (B.G.F.), and the University of Calgary, Calgary, AB (S. Ghosh) - all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W.); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V.); and Northwestern University, Evanston, IL (S.B.H.).
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Corporate Authors:
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TOUCHSTONE Study Group
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Źródło:
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The New England journal of medicine [N Engl J Med] 2016 May 05; Vol. 374 (18), pp. 1754-62.
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Typ publikacji:
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Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: Boston, Massachusetts Medical Society.
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MeSH Terms:
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Colitis, Ulcerative/*drug therapy
Indans/*therapeutic use
Oxadiazoles/*therapeutic use
Receptors, Lysosphingolipid/*agonists
Administration, Oral ; Adolescent ; Adult ; Aged ; Double-Blind Method ; Female ; Humans ; Indans/adverse effects ; Induction Chemotherapy ; Maintenance Chemotherapy ; Male ; Middle Aged ; Oxadiazoles/adverse effects ; Remission Induction
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Contributed Indexing:
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Investigator: M Sparrow; S Vermeire; J Churchev; I Kotzev; D Takov; B Dragomirov; B Vladimirov; S Stoynov; Z Krastev; L Yordanova; K Tchernev; B Feagan; B Feagan; D Karamanolis; E Tsianos; S Potamianos; R Schnabel; GG Kiss; T Gyökeres; A Taller; D Rachmilewitz; E Goldin; Y Avni; R Oren; F Konikoff; O Segol; JS Delgado; BI Jang; HJ Kim; HS Kim; SH Park; JH Cheon; DI Park; SA Jung; KC Huh; KM Lee; M Lowenberg; F Wolfhagen; R Ouwendijk; M Schultz; S Inns; I Wallace; M Haines; R Gearry; M Wisniewska-Jarosinska; R Petryka; K Niezgoda; K Janik; M Orlowski; K Stec-Michalska; R Filip; A Janke; M Gonciarz; J Huk; T Tacikowski; J Rozciecha; E Bunkova; V Simanenkov; O Alexeeva; M Osipenko; M Livzan; L Lenskaya; M Pesegova; A Gordienko; A Yakovlev; A Doletskiy; I Bunganic; M Gregus; J Osvaldova; A Sokol; O Abrahamovych; O Golovchenko; N Kharchenko; S Prokopchuk; G Fadieienko; L Glushko; Y Lymar; M Stanislavchuk; V Vdovychenko; A Dorofeev; K Mylytsya; O Datsenko; Y Martynovskyi; S Vasylyuk; D Wolf; M DeMicco; R Hardi; P Bekal; S Katz; KL Isaacs; W Sandborn; C Devereaux; M Noar; RP Fogel; W Sandborn; B Feagan; D Wolfe; S Hanauer; S Ghosh; S Vermeire; G D'Haens
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Molecular Sequence:
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ClinicalTrials.gov NCT01647516
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Substance Nomenclature:
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0 (Indans)
0 (Oxadiazoles)
0 (Receptors, Lysosphingolipid)
Z80293URPV (ozanimod)
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Entry Date(s):
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Date Created: 20160505 Date Completed: 20160524 Latest Revision: 20220410
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Update Code:
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20240104
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DOI:
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10.1056/NEJMoa1513248
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PMID:
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27144850
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Background: Ozanimod (RPC1063) is an oral agonist of the sphingosine-1-phosphate receptor subtypes 1 and 5 that induces peripheral lymphocyte sequestration, potentially decreasing the number of activated lymphocytes circulating to the gastrointestinal tract.
Methods: We conducted a double-blind, placebo-controlled phase 2 trial of ozanimod in 197 adults with moderate-to-severe ulcerative colitis. Patients were randomly assigned, in a 1:1:1 ratio, to receive ozanimod at a dose of 0.5 mg or 1 mg or placebo daily for up to 32 weeks. The Mayo Clinic score was used to measure disease activity on a scale from 0 to 12, with higher scores indicating more severe disease; subscores range from 0 to 3, with higher scores indicating more severe disease. The primary outcome was clinical remission (Mayo Clinic score ≤2, with no subscore >1) at 8 weeks.
Results: The primary outcome occurred in 16% of the patients who received 1 mg of ozanimod and in 14% of those who received 0.5 mg of ozanimod, as compared with 6% of those who received placebo (P=0.048 and P=0.14, respectively, for the comparison of the two doses of ozanimod with placebo). Differences in the primary outcome between the group that received 0.5 mg of ozanimod and the placebo group were not significant; therefore, the hierarchical testing plan deemed the analyses of secondary outcomes exploratory. Clinical response (decrease in Mayo Clinic score of ≥3 points and ≥30% and decrease in rectal-bleeding subscore of ≥1 point or a subscore ≤1) at 8 weeks occurred in 57% of those receiving 1 mg of ozanimod and 54% of those receiving 0.5 mg, as compared with 37% of those receiving placebo. At week 32, the rate of clinical remission was 21% in the group that received 1 mg of ozanimod, 26% in the group that received 0.5 mg of ozanimod, and 6% in the group that received placebo; the rate of clinical response was 51%, 35%, and 20%, respectively. At week 8, absolute lymphocyte counts declined 49% from baseline in the group that received 1 mg of ozanimod and 32% from baseline in the group that received 0.5 mg. The most common adverse events overall were anemia and headache.
Conclusions: In this preliminary trial, ozanimod at a daily dose of 1 mg resulted in a slightly higher rate of clinical remission of ulcerative colitis than placebo. The trial was not large enough or of sufficiently long duration to establish clinical efficacy or assess safety. (Funded by Receptos; TOUCHSTONE ClinicalTrials.gov number, NCT01647516.).
Comment in: N Engl J Med. 2016 Aug 25;375(8):e17. (PMID: 27557326)
Comment in: N Engl J Med. 2016 Aug 25;375(8):e17. (PMID: 27557327)
