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Failure of interleukin 13 blockade in ulcerative colitis
  1. Herbert Tilg1,
  2. Arthur Kaser2
  1. 1Department of Internal Medicine I, Gastroenterology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria
  2. 2Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
  1. Correspondence to Professor Herbert Tilg, Department of Internal Medicine I, Medical University Innsbruck, Innsbruck 6020, Austria; Herbert.Tilg{at}i-med.ac.at; Professor Arthur Kaser, Div of Gastroenterology and Hepatology, Dept of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UK; ak729@cam.ac.uk

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Contrary to a decade ago, clinical development in ulcerative colitis (UC) has become highly active with multiple promising innovative assets currently in early and late phase clinical studies. The anti-integrin α4β7 monoclonal antibody vedolizumab has been leading this wave, and has received marketing authorisation by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) based on an excellent efficacy and safety record.

One of the targets that had raised high hopes several years ago was interleukin 13 (IL-13), together with IL-4 and IL-5 the signature cytokine of a T helper 2 (Th2) immune response. As such, its blockade was hypothesised as a brilliant therapeutic strategy in diseases such as allergic asthma and UC. However, in this issue of Gut, results from a trial with anrukinzumab in active UC are reported,1 which, together with results of a trial with tralokinumab reported in the January issue,2 crush enthusiasm for anti-IL-13 blockade as a therapeutic strategy in UC.

Anrukinzumab is a humanised IgG1 antibody, which binds IL-13 and inhibits IL-13's binding to the IL-4Rα chain, part of the IL-13 receptor complex, while it does not block binding of IL-13 to IL-13Rα1 or α2 chains. In a randomised, double-blind, phase IIa study conducted in 38 centres in 10 countries, a total of 84 patients (out of 152 screened) were randomised to three doses (200 mg, 400 mg and 600 mg) anrukinzumab or placebo, with five doses of study medication administered over a 14-week treatment period.1 As a first in a UC trial, fold-change from baseline faecal calprotectin at week 14 was chosen as the primary end point—which turned out not to be significantly different for the three treatment …

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