Ustekinuma b for Crohn's Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, a Nationwide Prospective Observational Cohort Study.

Tessa Straatmijer,Gerard Dijkstra,Vince B C Biemans,Nanne K H De Boer,Sander Van Der Marel,Frank Hoentjen,Marjolijn Duijvestein,Marieke Pierik,Bas Oldenburg,Annemarie C De Vries ,Cyriel Y Ponsioen ,Marijn C Visschedijk ,Rachel West ,Jeroen M Jansen ,J Haans ,Alexander Bodelier ,Willemijn A Van Dop ,P W J Maljaars ,Christien J Van Der Woude ,Andrea E Van Der Meulen‐De Jong

doi:10.1093/ecco-jcc/jjab081

Abstract

Ustekinumab is a monoclonal antibody that selectively targets p40, a shared subunit of the cytokines interleukin [IL]-12 and IL-23. It is registered for the treatment of inflammatory bowel diseases. We assessed the 2-year effectiveness and safety of ustekinumab in a real world, prospective cohort of patients with Crohn's disease [CD]. Patients who started ustekinumab were prospectively enrolled in the nationwide Initiative on Crohn and Colitis [ICC] Registry. At weeks 0, 12, 24, 52 and 104, clinical remission Harvey Bradshaw Index≤ 4 points], biochemical remission (faecal calprotectin ≤ 200 μg/g and/or C-reactive protein ≤5 mg/L], perianal fistula remission, extra-intestinal manifestations, ustekinumab dosage and safety outcomes were determined. The primary outcome was corticosteroid-free clinical remission at week 104. In total, 252 CD patients with at least 2 years of follow-up were included. Of all included patients, the proportion of patients in corticosteroid-free clinical remission was 32.3% [81/251], 41.4% [104/251], 39% [97/249] and 34.0% [84/247] at weeks 12, 24, 52 and 104, respectively. In patients with combined clinical and biochemical disease activity at baseline [n = 122], the corticosteroid-free clinical remission rates were 23.8% [29/122], 35.2% [43/122], 40.0% [48/120] and 32.8% [39/119] at weeks 12, 24, 52 and 104, respectively. The probability of remaining on ustekinumab treatment after 52 and 104 weeks in all patients was 64.3% and 54.8%, respectively. The main reason for discontinuing treatment after 52 weeks was loss of response [66.7%]. No new safety issues were observed. After 104 weeks of ustekinumab treatment, one-third of CD patients were in corticosteroid-free clinical remission.

Highlights

Crohn’s disease [CD] is a chronic inflammatory bowel disease [IBD] with heterogeneous symptoms including abdominal pain, diarrhoea, rectal bleeding and malnutrition
After 104 weeks of ustekinumab treatment, one-third of CD patients were in corticosteroid-free clinical remission
The effectiveness of ustekinumab in inducing and maintaining clinical remission in CD patients has been demonstrated in the IM-UNITI trials.[2]

Summary

Introduction

Crohn’s disease [CD] is a chronic inflammatory bowel disease [IBD] with heterogeneous symptoms including abdominal pain, diarrhoea, rectal bleeding and malnutrition. One of the newer therapeutic options for CD is ustekinumab, a fully human monoclonal antibody targeting the p40 subunit of interleukin [IL]-12 and IL-23. This inhibits T-helper 1 and T-helper 17 pathways involved in CD. Real-world data with long-term follow-up to assess effectiveness, safety and loss of response is required given the need for continued treatment in CD. If predictors of response or intolerance are identified, therapy can be applied to those patients who are likely to benefit, which leads to improved outcomes of IBD

Methods

Results

Conclusion