TY - JOUR
T1 - Mongersen, an oral SMAD7 antisense oligonucleotide, and crohn's disease
AU - Monteleone, Giovanni
AU - Neurath, Markus F.
AU - Ardizzone, Sandro
AU - Di Sabatino, Antonio
AU - Fantini, Massimo C.
AU - Castiglione, Fabiana
AU - Scribano, Maria L.
AU - Armuzzi, Alessandro
AU - Caprioli, Flavio
AU - Sturniolo, Giacomo C.
AU - Rogai, Francesca
AU - Vecchi, Maurizio
AU - Atreya, Raja
AU - Bossa, Fabrizio
AU - Onali, Sara
AU - Fichera, Maria
AU - Corazza, Gino R.
AU - Biancone, Livia
AU - Savarino, Vincenzo
AU - Pica, Roberta
AU - Orlando, Ambrogio
AU - Pallone, Francesco
PY - 2015/3/19
Y1 - 2015/3/19
N2 - Background Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7. Methods In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28. Results The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P
AB - Background Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7. Methods In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28. Results The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P
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U2 - 10.1056/NEJMoa1407250
DO - 10.1056/NEJMoa1407250
M3 - Article
C2 - 25785968
AN - SCOPUS:84925064199
VL - 372
SP - 1104
EP - 1113
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 12
ER -