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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)77-86.e6
JournalGastroenterology
Volume153
Issue number1
DOIs
Publication statusPublished - Jul 1 2017

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Interleukin-23
Crohn Disease
Safety
Antibodies
Placebos
Nasopharyngitis
Tumor Necrosis Factor-alpha
Cytokines
Headache
Therapeutics
Monoclonal Antibodies
Confidence Intervals
Serum

Keywords

  • Clinical Trial
  • IL22
  • IL23
  • Phase II

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients With Moderate to Severe Crohn's Disease : A Phase 2a Study. / Sands, Bruce E.; Chen, Jingjing; Feagan, Brian G.; Penney, Mark; Rees, William A.; Danese, Silvio; Higgins, Peter D.R.; Newbold, Paul; Faggioni, Raffaella; Patra, Kaushik; Li, Jing; Klekotka, Paul; Morehouse, Chris; Pulkstenis, Erik; Drappa, Jörn; van der Merwe, René; Gasser, Robert A.

In: Gastroenterology, Vol. 153, No. 1, 01.07.2017, p. 77-86.e6.

Research output: Contribution to journalArticle

Sands, BE, Chen, J, Feagan, BG, Penney, M, Rees, WA, Danese, S, Higgins, PDR, Newbold, P, Faggioni, R, Patra, K, Li, J, Klekotka, P, Morehouse, C, Pulkstenis, E, Drappa, J, van der Merwe, R & Gasser, RA 2017, 'Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients With Moderate to Severe Crohn's Disease: A Phase 2a Study', Gastroenterology, vol. 153, no. 1, pp. 77-86.e6. https://doi.org/10.1053/j.gastro.2017.03.049
Sands, Bruce E. ; Chen, Jingjing ; Feagan, Brian G. ; Penney, Mark ; Rees, William A. ; Danese, Silvio ; Higgins, Peter D.R. ; Newbold, Paul ; Faggioni, Raffaella ; Patra, Kaushik ; Li, Jing ; Klekotka, Paul ; Morehouse, Chris ; Pulkstenis, Erik ; Drappa, Jörn ; van der Merwe, René ; Gasser, Robert A. / Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients With Moderate to Severe Crohn's Disease : A Phase 2a Study. In: Gastroenterology. 2017 ; Vol. 153, No. 1. pp. 77-86.e6.
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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.",
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T2 - A Phase 2a Study

AU - Sands, Bruce E.

AU - Chen, Jingjing

AU - Feagan, Brian G.

AU - Penney, Mark

AU - Rees, William A.

AU - Danese, Silvio

AU - Higgins, Peter D.R.

AU - Newbold, Paul

AU - Faggioni, Raffaella

AU - Patra, Kaushik

AU - Li, Jing

AU - Klekotka, Paul

AU - Morehouse, Chris

AU - Pulkstenis, Erik

AU - Drappa, Jörn

AU - van der Merwe, René

AU - Gasser, Robert A.

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N2 - 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.

AB - 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.

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