Silvio Danese1, Janusz Rudziński2, Wolfgang Brandt3, Jean-Louis Dupas4, Laurent Peyrin-Biroulet5, Yoram Bouhnik6, Dariusz Kleczkowski7, Peter Uebel8, Milan Lukas9, Mikael Knutsson10, Fredrik Erlandsson10, Mark Berner Hansen10, Satish Keshav11. 1. Istituto Clinico Humanitas, Milan, Italy. 2. 10 Wojskowy Szpital Kliniczny z Polikliniką, Bydgoszcz, Poland. 3. Facharzt für Innere Medizin, Potsdam, Germany. 4. Centre Hospitalier Universitaire, Amiens, France. 5. Inserm U954 and Department of Gastroenterology, Université de Lorraine, Vandœuvre-lès-Nancy, France. 6. Hôpital Beaujon, Paris, France. 7. Endoskopia Sp. z o. o., Sopot, Poland. 8. P. Uebel Haus der Gesundheit, Ludwigshafen, Germany. 9. IBD Clinical and Research Centre, ISCARE Lighthouse and 1st Medical Faculty, Charles University, Prague, Czech Republic. 10. AstraZeneca R&D, Mölndal, Sweden. 11. Department of Medicine, John Radcliffe Hospital, Oxford, UK.
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. DESIGN: 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. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number: NCT01482884. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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. DESIGN: 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. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number: NCT01482884. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: Stefan Wirtz; Vanessa Popp; Markus Kindermann; Katharina Gerlach; Benno Weigmann; Stefan Fichtner-Feigl; Markus F Neurath Journal: Nat Protoc Date: 2017-06-01 Impact factor: 13.491
Authors: Vipul Jairath; Guangyong Zou; Claire E Parker; John K Macdonald; Mahmoud H Mosli; Reena Khanna; Lisa M Shackelton; Margaret K Vandervoort; Turki AlAmeel; Mohammad Al Beshir; Majid AlMadi; Talal Al-Taweel; Nathan S S Atkinson; Sujata Biswas; Thomas P Chapman; Parambir S Dulai; Mark A Glaire; Daniel Hoekman; Andreas Koutsoumpas; Elizabeth Minas; Mark A Samaan; Simon Travis; Geert D'Haens; Barrett G Levesque; William J Sandborn; Brian G Feagan Journal: J Crohns Colitis Date: 2016-01-07 Impact factor: 9.071