title: Tralokinumab for moderate-to-severe UC: a randomised, double-blind, placebo-controlled, phase IIa study.
abstract: OBJECTIVE
  Interleukin-13 (IL-13) has been implicated as a key driver of UC. This trial evaluates the efficacy and safety of tralokinumab, an IL-13-neutralising antibody, as add-on therapy in adults with moderate-to-severe UC despite standard treatments.
  
  
  METHODS
  Non-hospitalised adults with UC (total Mayo score ≥6) were randomised to receive tralokinumab 300 mg or placebo subcutaneously every 2 weeks for 12 weeks. The primary end point was the rate of clinical response at week 8. Secondary efficacy end points included clinical remission and mucosal healing rates at week 8 and changes in total Mayo score, total modified Riley score, partial Mayo score and disease activity markers.
  
  
  RESULTS
  Clinical response rate was 38% (21/56) for tralokinumab vs. 33% (18/55) for placebo (p=0.406). Clinical remission rate was 18% (10/56) vs. 6% (3/55) (p=0.033) and mucosal healing rate was 32% (18/56) vs. 20% (11/55) (p=0.104) for tralokinumab vs placebo. Changes to week 8 in total Mayo score and total modified Riley score were similar for tralokinumab and placebo (least-squares mean difference between groups: -0.49 (p=0.394) and 0.25 (p=0.449), respectively). Partial Mayo score at week 4 was lower with tralokinumab than placebo (least-squares mean difference between groups: -0.90 (p=0.041)). No consistent patterns were observed for disease activity markers. Tralokinumab had an acceptable safety profile.
  
  
  CONCLUSIONS
  Add-on therapy with tralokinumab did not significantly improve clinical response. However, the higher clinical remission rate with tralokinumab than placebo suggests that tralokinumab may benefit some patients with UC. Tralokinumab was well tolerated.
  
  
  BACKGROUND
  ClinicalTrials.gov number: NCT01482884.
authors.affiliation: Istituto Clinico Humanitas, Milan, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Danese
authors.affiliation: 10 Wojskowy Szpital Kliniczny z Polikliniką, Bydgoszcz, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Rudziński
authors.affiliation: Facharzt für Innere Medizin, Potsdam, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brandt
authors.affiliation: Centre Hospitalier Universitaire, Amiens, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Dupas
authors.affiliation: Inserm U954 and Department of Gastroenterology, Université de Lorraine, Vandœuvre-lès-Nancy, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.affiliation: Hôpital Beaujon, Paris, France.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Bouhnik
authors.affiliation: Endoskopia Sp. z o. o., Sopot, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Kleczkowski
authors.affiliation: P. Uebel Haus der Gesundheit, Ludwigshafen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Uebel
authors.affiliation: IBD Clinical and Research Centre, ISCARE Lighthouse and 1st Medical Faculty, Charles University, Prague, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Lukas
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Knutsson
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Erlandsson
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Mark Berner
authors.initials: MB
authors.lastname: Hansen
authors.affiliation: Department of Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: Satish
authors.initials: S
authors.lastname: Keshav
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014945:Wound Healing; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents; C574065:tralokinumab
keywords: ULCERATIVE COLITIS