title: Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients With Moderate to Severe Crohn's Disease: A Phase 2a Study.
abstract: MEDI2070 is a human monoclonal antibody that selectively inhibits interleukin 23 (IL23), a cytokine implicated in the pathogenesis of Crohn's disease (CD). We analyzed its safety and efficacy in treatment of CD in a phase 2a study.
  
  
  
  We conducted a double-blind, placebo-controlled study of 119 adults with moderate to severe CD failed by treatment with tumor necrosis factor antagonists. Patients were randomly assigned (1:1) to groups given MEDI2070 (700 mg) or placebo intravenously at weeks 0 and 4. Patients received open-label MEDI2070 (210 mg) subcutaneously every 4 weeks from weeks 12 to 112. The CD Activity Index was used to measure disease activity.
  
  
  
  The primary outcome, clinical response (either a 100-point decrease in CD Activity Index score from baseline or clinical remission, defined as CD Activity Index score <150) at week 8 occurred in 49.2% of patients receiving MEDI2070 (n = 59) compared with 26.7% receiving placebo (n = 60; absolute difference, 22.5%; 95% confidence interval, 5.6%-39.5%; P = .010). Clinical response at week 24 occurred in 53.8% of patients who continued to receive open-label MEDI2070 and in 57.7% of patients who had received placebo during the double-blind period and open-label MEDI2070 thereafter. The most common adverse events were headache and nasopharyngitis. Higher baseline serum concentrations of IL22, a cytokine whose expression is induced by IL23, were associated with greater likelihood of response to MEDI2070 compared with placebo.
  
  
  
  In a phase 2a trial of patients with moderate to severe Crohn's disease who had failed treatment with tumor necrosis factor antagonists, 8 and 24 weeks of treatment with MEDI2070 were associated with clinical improvement. ClinicalTrials.gov ID: NCT01714726.
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: bruce.sands@mssm.edu.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Sands
authors.affiliation: MedImmune, Gaithersburg, Maryland.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Robarts Clinical Trials, University of Western Ontario, London, Ontario.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: MedImmune, Cambridge, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Penney
authors.affiliation: MedImmune, Gaithersburg, Maryland.
authors.forename: William A
authors.initials: WA
authors.lastname: Rees
authors.affiliation: Humanitas Clinical and Research Center, Milan, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Danese
authors.affiliation: University of Michigan, Ann Arbor, Michigan.
authors.forename: Peter D R
authors.initials: PDR
authors.lastname: Higgins
authors.affiliation: MedImmune, Gaithersburg, Maryland.
authors.forename: Paul
authors.initials: P
authors.lastname: Newbold
authors.affiliation: MedImmune, Mountain View, California.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Faggioni
authors.affiliation: MedImmune, Gaithersburg, Maryland.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Patra
authors.affiliation: MedImmune, Mountain View, California.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Amgen, Thousand Oaks, California.
authors.forename: Paul
authors.initials: P
authors.lastname: Klekotka
authors.affiliation: MedImmune, Gaithersburg, Maryland.
authors.forename: Chris
authors.initials: C
authors.lastname: Morehouse
authors.affiliation: MedImmune, Gaithersburg, Maryland.
authors.forename: Erik
authors.initials: E
authors.lastname: Pulkstenis
authors.affiliation: MedImmune, Gaithersburg, Maryland.
authors.forename: Jörn
authors.initials: J
authors.lastname: Drappa
authors.affiliation: MedImmune, Cambridge, United Kingdom.
authors.forename: René
authors.initials: R
authors.lastname: van der Merwe
authors.affiliation: MedImmune, Gaithersburg, Maryland.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Gasser
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D053759:Interleukin-23 / Q000037:antagonists & inhibitors; D007378:Interleukins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009304:Nasopharyngitis / Q000139:chemically induced; D019233:Retreatment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053759:Interleukin-23; D007378:Interleukins; D000097043:Interleukin-22; C000622252:MEDI2070
keywords: Clinical Trial; IL22; IL23; Phase II