Ustekinumab (UST) binds to the p40 subunit of IL12 and IL23 to prevent IL12RB1 cell-surface receptor activation and thus inhibits downstream inflammatory signalling. It is approved for moderately to severely active Crohn’s disease (NICE TA456). We assessed the clinical outcomes and safety of UST in a ‘real-world’ cohort of refractory Crohn’s disease patients treated at a single UK centre.Methods
We retrospectively collected data from the electronic records of Crohn’s disease patients treated with UST at a single UK IBD tertiary referral centre. Patient demographics and adverse events were recorded. Clinical response to UST was evaluated at baseline and follow up using Harvey-Bradshaw Index (HBI) scores, C reactive protein (CRP), and faecal calprotectin (FC). Paired Student’s T Tests were used to determine statistical significance.Results
26 patients (mean age 36 years; age 18–62 years; M:F ratio=1:1.6) with a variety of Crohn’s disease phenotypes (L1=8; L2=6; L3=12) were treated with UST. 9 patients (35%) had stricturing disease and 5 patients (19%) penetrating disease. All patients had failed at least one anti-TNF agent. 15 patients (58%) had failed two anti-TNF agents, and 11 (42%) had failed an anti-TNF and subsequent vedolizumab therapy. 7 patients (27%) received immunomodulatory co-therapy (AZA=5; MTX=2), and 11 (42%) received bridging steroids.Results
12 week data was available for 20 patients. At 12 weeks, mean HBI significantly improved (5 vs 9; p<0.05). There was reduction in mean FC (763 vs 1026; ns), but no change in mean CRP (14 vs 11; ns). 10 patients (50%) demonstrated subjective and objective (FC +/-CRP +/- endoscopic) response to therapy. 6 of these patients received bridging steroids, of which all had reduced and 4 had completed their steroid course. Of all treated patients 2 discontinued UST (recurrence of a transitional cell carcinoma; primary non-response to therapy requiring surgery), and side effects were reported in 2 patients (Bell’s Palsy; lower respiratory tract infection).Conclusions
UST appears clinically effective and safe in this cohort of treatment-refractory Crohn’s disease patients after 12 weeks of therapy. Future work to combine ‘real world’ data and to assess longer term outcomes will help us to better understand and place the use of UST in the management of Crohn’s disease.