Gastrointestinal Immunopathology Lab and IBD Unit, Humanitas Clinical and Research Center and Humanitas University, Milan, Italy.
Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium.
Nature Coast Clinical Research, Inverness, Florida, USA.
Inflammatory Bowel Disease Clinic, University of Calgary, Calgary, Canada.
Department of Gastroenterology and Hepatology, University of Zürich, Zürich, Switzerland.
Division of Gastroenterology, Rabin Medical Center, University of Tel-Aviv, Petah Tikva, Israel.
UOC Gastroenterologia, AO San Camillo Forlanini, Rome, Italy.
Lille University School of Medicine, University of Lille, Inserm U995, Lille, France.
Inflammatory Bowel Diseases Service, Concord Hospital, Sydney, New South Wales, Australia.
Formerly of Worldwide Research and Development, Pfizer Inc, Cambridge, Massachusetts, USA.
Worldwide Research and Development, Pfizer Inc, Cambridge, Massachusetts, USA.
Worldwide Research and Development, Pfizer Inc, Collegeville, Pennsylvania, USA.
Department of Medicine I, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Kiel, Germany.
Neutralising pro-inflammatory interleukin-6 (IL-6) may effectively treat Crohn's disease (CD). Effects of PF-04236921, an anti-IL-6 antibody, in adults with CD are reported.
Parallel-group, dose-ranging, double-blind trial with 4-week screening and 12-week treatment periods. After induction, patients entered 28-week follow-up or 48-week open-label extension (OLE) with 28-week follow-up. Adults with confirmed CD and inadequate response to anti-tumour necrosis factor (TNF) therapy were included. Induction study: 249 patients randomised 1:1:1:1 to placebo, PF-04236921 10, 50 or 200 mg by subcutaneous injection on days 1 and 28. OLE study: PF-04236921 50 mg every 8 weeks up to six doses followed by 28-week follow-up.
247 patients were randomised and received treatment in the induction study. The 200 mg dose was discontinued due to safety findings in another study (NCT01405196) and was not included in the primary efficacy analysis. Crohn's Disease Activity Index (CDAI)-70 response rates with PF-04236921 50 mg were significantly greater than placebo at weeks 8 (49.3% vs 30.6%, P<0.05) and 12 (47.4% vs 28.6%, P<0.05) and met the primary end point. Week 12 CDAI remission rates with PF-04236921 50 mg and placebo were 27.4% and 10.9%, respectively (16.5% difference; P<0.05). 191 subjects received treatment in the OLE. Common treatment-emergent and serious adverse events in both studies included worsening CD, abdominal pain and nasopharyngitis.
PF-04236921 50 mg induced clinical response and remission in refractory patients with moderate-to-severe CD following failure of anti-TNF therapy. GI abscess and perforation were observed, a specific focus of attention during future clinical development.
TRIAL REGISTRATION NUMBER:
NCT01287897 and NCT01345318.