TY - JOUR
T1 - Ozanimod induction and maintenance treatment for ulcerative colitis
AU - TOUCHSTONE Study Group
AU - Sandborn, William J.
AU - Feagan, Brian G.
AU - Wolf, Douglas C.
AU - D'Haens, Geert
AU - Vermeire, Severine
AU - Hanauer, Stephen B.
AU - Ghosh, Subrata
AU - Smith, Heather
AU - Cravets, Matthew
AU - Frohna, Paul A.
AU - Aranda, Richard
AU - Gujrathi, Sheila
AU - Olson, Allan
AU - Sparrow, Miles
AU - Churchev, Jordan
AU - Kotzev, Iskren
AU - Takov, Dimitar
AU - Dragomirov, Borislav
AU - Vladimirov, Borislav
AU - Stoynov, Simeon
AU - Krastev, Zahariy
AU - Yordanova, Liliana
AU - Tchernev, Konstantin
AU - Karamanolis, Dimitrios
AU - Tsianos, Epameinondas
AU - Potamianos, Spyridon
AU - Schnabel, Róbert
AU - G. Kiss, Gyula
AU - Gyökeres, Tibor
AU - Taller, András
AU - Rachmilewitz, Daniel
AU - Goldin, Eran
AU - Avni, Yona
AU - Oren, Ran
AU - Konikoff, Fred
AU - Segol, Ori
AU - Delgado, Jorge Shmuel
AU - Jang, Byung Ik
AU - Kim, Hyo Jong
AU - Kim, Hyun Soo
AU - Park, Sang Hyoung
AU - Cheon, Jae Hee
AU - Park, Dong Il
AU - Jung, Sung Ae
AU - Huh, Kyu Chan
AU - Lee, Kang Moon
AU - Lowenberg, Marc
AU - Wolfhagen, Frank
AU - Ouwendijk, R.
AU - Schultz, Michael
N1 - Publisher Copyright:
Copyright © 2016 Massachusetts Medical Society. All rights reserved.
PY - 2016/5/5
Y1 - 2016/5/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84968903266&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1513248
DO - 10.1056/NEJMoa1513248
M3 - Article
C2 - 27144850
AN - SCOPUS:84968903266
SN - 0028-4793
VL - 374
SP - 1754
EP - 1762
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 18
ER -