- Authors
- Sands, Bruce E., MD; Chen, Jingjing, PhD; Feagan, Brian G., MD; Penney, Mark, PhD; Rees, William A., Ph.D; Danese, Silvio, MD, PhD; Higgins, Peter D.R., MD, PhD; Newbold, Paul, PhD; Faggioni, Raffaella, PhD; Patra, Kaushik, PhD; Li, Jing, PhD; Klekotka, Paul, MD, PhD; Morehouse, Chris, MS; Pulkstenis, Erik, PhD; Drappa, Jörn, MD, PhD; van der Merwe, René, MBChB; Gasser, Robert A., MD
- Part of
- Gastroenterology (New York, N.Y. 1943), 2017-07, Vol.153 (1), p.77-86.e6
- Abstract
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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 (TNF) 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 (CDAI) was used to measure disease activity. Results The primary outcome, clinical response (either a 100-point decrease in CDAI score from baseline or clinical remission, defined as CDAI score below 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% CI, 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 to placebo. Conclusions In a phase 2a trial of patients with moderate to severe Crohn’s disease who had failed treatment with TNF antagonists, 8 and 24 weeks of treatment with MEDI2070 were associated with clinical improvement. Clinicaltrials.gov no: NCT01714726.
- Subjects
- Adult; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Clinical Trial; Crohn Disease - drug therapy; Double-Blind Method; Female; Gastroenterology and Hepatology; Headache - chemically induced; Humans; IL22; IL23; Interleukin-22; Interleukin-23 - antagonists & inhibitors; Interleukins - blood; Male; Middle Aged; Nasopharyngitis - chemically induced; Phase II; Retreatment; Severity of Illness Index; Treatment Outcome; Young Adult