Efficacy and safety of mirikizumab in a randomized phase 2 study of patients with Ulcerative Colitis

Sandborn WJ, Ferrante M, Bhandari BR, Berliba E, Feagan BG, Hibi T, Tuttle JL, Klekotka P, Friedrich S, Durante M, Morgan-Cox M, Laskowski J, Schmitz J, D'Haens GR

Gastroenterology. 2019;doi: https://doi.org/10.1053/j.gastro.2019.08.043. [Epub ahead of print]

Introduction

Hajir Ibraheim © Hajir Ibraheim

Interleukin-23 (IL23) contributes to the pathogenesis of chronic inflammatory diseases, including Ulcerative Colitis (UC), by maintaining and amplifying T helper 17 cells and stimulating many innate immune cells. IL-23 is a heterodimeric cytokine composed of a p40 subunit (shared by IL12) and a p19 subunit (IL-23p19). Ustekinumab, a monoclonal antibody targeting the shared p40 subunit, is effective for treatment of Crohn’s Disease (CD) and psoriasis [1–3]. However, studies in patients with psoriasis have suggested that selective targeting of the IL23 pathway by blocking IL-23p19 is more effective than ustekinumab [4, 5]. Whilst promising phase 2 results have been observed in CD patients following treatment targeting IL-23p19 [6, 7], the role of this therapeutic strategy in UC is unknown. Mirikizumab (LY3074828) is a humanised immunoglobulin G4 (IgG4)-variant monoclonal antibody that binds to the IL-23p19 subunit. The current study evaluated the efficacy and safety of mirikizumab for the treatment of patients with moderate-to-severely active UC. 

Catherine Walsh © Catherine Walsh

Ireland

Name of group: The IBD section of the British Society of Gastroenterology (BSG).
Number of active members: 60
Number of meetings per year: 2
President and Secretary: 
Emma Anderson, Chairperson
Aine Keogh, Secretary
Joanne Rae, Assistant Secretary 

National Representatives: Aine Keogh and Cathy Walsh
Joined ECCO in: 2004
Incidence of IBD in the country: Approx. 35,000

Dominik Bettenworth  © Dominik Bettenworth

Raja Atreya © Raja Atreya

Germany

Name of group: The “Competence Network IBD (Kompetenznetz Darmerkrankungen)” is the interest group that oversees IBD-related activities in Germany. It incorporates the German IBD Study Group (GISG), which conducts collaborative IBD studies in Germany, the “German work group for Inflammatory Bowel Diseases (DACED), which is the IBD research organisation, the WG Bildgebung, which focusses on imaging-related projects, and the WG Zöliakie, which concentrates on coeliac disease. The “Competence Network IBD” also collaborates with diverse other groups (e.g. FA-CED, which represents IBD study nurses).

Number of active members: The Competence Network IBD comprises more than 700 members while the GISG has more than 170 members. There are 226 ECCO Members in Germany.

Number of meetings per year: There is one annual meeting of the Competence Network IBD that takes place during the yearly meeting of the German Society for Gastroenterology, Digestive and Metabolic Diseases.

President and Secretary: The current chairperson of the Competence Network IBD is Bernd Bokemeyer (Minden).

National Representatives: Raja Atreya, Erlangen and Dominik Bettenworth, Münster.

Joined ECCO in: Germany has been a proud member of ECCO since 2004.

Incidence of IBD in the country: 3–3.9/100,000 in Ulcerative Colitis and 6.6/100,000 in Crohn’s Disease

Edouard Louis © ECCO

The BIOCYCLE project has now been ongoing for over 4 years. This project, funded by the European commission under the Horizon 2020 program, aims at exploring different aspects of the question of treatment de-escalation in moderate-severe Crohn’s disease, first requiring a combination therapy with anti-TNF and antimetabolites to control the disease. Once the disease has been stabilized, an unsolved question is to whether it is possible to de-escalate therapy. This question is important for several reasons including safety, tolerance, quality of life or costs to name the most prominent. Biocycle includes a randomized three arms, controlled clinical trial, called SPARE, on 200 patients in 6 European countries (France, United Kingdom, Belgium, Sweden, The Netherlands and Germany) and Australia, several patients and health care providers’ surveys in Europe and the USA, a biomarker research program and pharmaco-economic analysis. ECCO is mainly involved in the monitoring of the project (through the Sci Com and the Clin Com) and is the work package leader for dissemination of the results. Biocycle is a 7.5 years-long project and has been launched in April 2015.