P548 Ustekinumab shows favourable safety profile and drug persistence rates in patients with Crohn’s Disease – results from a tertiary IBD centre

Abstract

Abstract Background 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 biologic followed by a switch of class when patients lose response. Ustekinumab (UST), an IL12/23p40 antagonist is used in CD, often after anti-TNF failure. The aim of the study was to report on outcomes of UST therapy with a median follow-up period of nearly 24 months. Methods All CD patients who commenced UST therapy were identified from EMR at two tertiary referral centers 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, endoscopic data, and sustained maintenance of UST. Statistical analysis was carried out using the IBM® SPSS® Statistics software package Version: 28.0.0.0. Results A total of 249 CD patients (M=133 (53%); median age 41 years) were included, with a median follow-up period of nearly 24 months (5-79 months). 94 (38%) patients had stricturing (B2), penetrating (B3) and perianal phenotype at baseline and 104 (42%) had undergone previous resection/s. 207 (83%) had documented moderate to severe disease activity and 211 (85%) patients were exposed to at least one biologic prior to treatment with UST. 66 (27%) patients were on concomitant thiopurines at the start of treatment. 224 (90%) patients in our cohort showed clinical response to UST and all remained on treatment at the end of 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 corresponding significant reduction in faecal calprotectin levels (median reduction: 506 mcg/g to 335 mcg at 104w; p<0.001). Only 10 (4%) patients had side-effects which were directly attributed to UST therapy. Conclusion UST is an effective therapeutic option in CD for both bio-naïve and previous biologic failure patients. Although our cohort had 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. UST has good drug-persistence rates making it economically feasible in the long term. Clinicians could safely continue UST for longer durations to manage CD.