P699 Ustekinumab therapy after biologic failure in patients with Crohn’s Disease – A real-world single centre experience​​

Majumder, S.(1,2,3)*;Bazarova, A.(4);Lorenzo Parigi, T.(1,3); Love , M.(5);Davis , J.(3);Ghosh, S.(6); Iacucci , M.(1,3,7);N. Shivaji, U.(1,3,7);

(1)University of Birmingham, Institute of Immunology and Immunotherapy, Birmingham, United Kingdom;(2)India Institute- University of Birmingham, Fellowship, Birmingham, United Kingdom;(3)University Hospitals Birmingham NHS Foundation Trust, Gastroenterology, Birmingham, United Kingdom;(4)Institute for Biological Physics University of Cologne, Biological Physics, Cologne, Germany;(5)University Hospitals Birmingham NHS Foundation Trust, Gastroenterology, Gastroenterology, United Kingdom;(6)College of Medicine and Health- University College Cork, APC Microbiome, Cork, Ireland;(7)National Institute for Health Research NIHR Birmingham Biomedical Research Centre- University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Institute of Immunology and Immunotherapy, Birmingham, United Kingdom;


Patients with Crohn’s disease (CD) often require multiple biological therapies due to loss of response. Anti-TNF drugs are generally used as first-line biologics followed by a switch of class. Ustekinumab (UST), an IL-12/23p40 antagonist is used often after anti-TNF failure. ​​The aim of the study was to report on the outcomes of UST therapy with a median follow-up period of nearly 24 months. ​


All CD patients who commenced UST therapy were identified from EMR at a tertiary referral centre between January 2017 and December 2021. All relevant demographic and clinical data were collected. Data on clinical response (defined as a downgrade in disease activity based on clinician assessment & biochemical parameters), steroid-free duration, and long-term response to UST at 52 and 104 weeks were recorded. The response was assessed clinically and supported by biomarkers, cross-sectional imaging, colonoscopic data, and sustained maintenance of UST. The statistical analysis was carried out using the IBM® SPSS® Statistics software package Version:​


A total of 147 CD patients (M=65, 44%; median age 38years) were included in the analysis with a median follow-up period of 24 months (range 5-67 months). 82 (56%) patients had stricturing (B2), penetrating (B3) and perianal phenotype at baseline, and 50 (34%) had undergone the previous resection/s. 109 (75%) had documented moderate to severe disease activity and 139 (95%) patients were exposed to at least one biologic prior to treatment with UST. A total of 34 (23%) patients were on concomitant thiopurines at the start of treatment. Among 147 patients in our cohort, 143 (97%) showed clinical response to UST and remained on treatment at the end of the follow-up period. The distribution of patients as per disease activity at baseline, 52 and 104 weeks is illustrated in Figure 1. An improvement in haemoglobin levels was observed post-therapy with UST, which was statistically significant at 104 weeks (p<0.001), with a corresponding significant reduction in faecal calprotectin levels (median reduction from 976 mcg/g  333 mcg at 104w; p<0.001). Only 13(8.8%) patients had side effects that were directly attributed to UST therapy.​


UST is an effective therapeutic option in patients with CD who have failed previous biologic therapy.​​ In our cohort with a large proportion of patients with complicated and refractory disease, clinical response was observed regardless of their previous exposure status to biologics, and disease phenotype. ​​UST appears to be well tolerated with a reasonable safety profile. ​​The consistent response rates even after prolonged treatment periods mean that clinicians could safely continue UST for longer durations, where options are limited.