title: Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy and safety from a phase IIa randomised multicentre study.
abstract: OBJECTIVE
  Interleukin 13 (IL-13) is thought to play a key role as an effector cytokine in UC. Anrukinzumab, a humanised antibody that inhibits human IL-13, was evaluated for the treatment of UC.
  
  
  METHODS
  In a multicentre, randomised, double-blind, placebo-controlled study, patients with active UC (Mayo score ≥4 and <10) were randomised to anrukinzumab 200, 400 or 600 mg or placebo. Patients received five intravenous administrations over 14 weeks. The primary endpoint was fold change from baseline in faecal calprotectin (FC) at Week 14. Secondary endpoints included safety, pharmacokinetics and IL-13 levels.
  
  
  RESULTS
  The modified intention-to-treat population included 84 patients (21 patients/arm). Fold change of FC from baseline at Week 14 was not significantly different for any treatment groups compared with the placebo. The study had a high dropout rate, in part, related to lack of efficacy. The exploratory comparisons of each dose were not significantly different from placebo in terms of change from baseline in total Mayo score, clinical response, clinical remission and proportion of subjects with mucosal healing. An increase in serum total IL-13 (free and bound to anrukinzumab) was observed for all anrukinzumab groups but not with placebo. This suggests significant binding of anrukinzumab to IL-13. The safety profile was not different between the anrukinzumab and placebo groups.
  
  
  CONCLUSIONS
  A statistically significant therapeutic effect of anrukinzumab could not be demonstrated in patients with active UC in spite of binding of anrukinzumab to IL-13.
  
  
  BACKGROUND
  ClinicalTrials.gov number NCT01284062.
authors.affiliation: McMaster University, Hamilton, Ontario, Canada Medical University of Vienna, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.affiliation: Hospital Clinic I Provincial de Barcelona, CIBERehd, IDIBAPS, Barcelona, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Panés
authors.affiliation: Premier Medical Group, Fishkill, New York, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Khurana
authors.affiliation: Szent János Hospital, Budapest, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Toth
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Hua
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Comer
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Hinz
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Page
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Margot
authors.initials: M
authors.lastname: O'Toole
authors.affiliation: InVentiv Health Clinical, Burlington, Massachusetts, USA.
authors.forename: Tara McDonnell
authors.initials: TM
authors.lastname: Moorehead
authors.affiliation: Pfizer CRDC, Shanghai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Pfizer CRDC, Shanghai, China.
authors.forename: YanHui
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Cataldi
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018793:Interleukin-13 / Q000037:antagonists & inhibitors* / Q000097:blood; D007958:Leukocyte Count; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; C578095:IL13 protein, human; D007166:Immunosuppressive Agents; D018793:Interleukin-13; D039841:Leukocyte L1 Antigen Complex; C000599521:anrukinzumab
keywords: INTERLEUKINS; ULCERATIVE COLITIS