Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients With Moderate to Severe Crohn's Disease: A Phase 2a Study.

Abstract

BACKGROUND & AIMS:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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: Bruce E Sands, Jingjing Chen, Brian G Feagan, Mark Penney, William A Rees, Silvio Danese, Peter D R Higgins, Paul Newbold, Raffaella Faggioni, Kaushik Patra, Jing Li, Paul Klekotka, Chris Morehouse, Erik Pulkstenis, Jörn Drappa, René van der Merwe, Robert A Gasser Jr
• Journal: Gastroenterology (Gastroenterology) Vol. 153 Issue 1 Pg. 77-86.e6 (Jul 2017) ISSN: 1528-0012 [Electronic] United States
• PMID: 28390867 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Interleukin-23
• Interleukins
• MEDI2070

Topics

• Adult
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Crohn Disease (drug therapy)
• Double-Blind Method
• Female
• Headache (chemically induced)
• Humans
• Interleukin-23 (antagonists & inhibitors)
• Interleukins (blood)
• Male
• Middle Aged
• Nasopharyngitis (chemically induced)
• Retreatment
• Severity of Illness Index
• Treatment Outcome
• Young Adult
• Interleukin-22