P472 Efficacy of intravenous ustekinumab re-induction in patients with Crohn’s disease with a loss of response

Ustekinumab (UST) has been shown to be effective in inducing and maintaining remission in patients with Crohn’s disease (CD). However, a significant number of patients do not respond or experience a secondary loss of response (LOR). We assessed the utility of UST intravenous (IV) re-induction (~6 mg/kg) to achieve clinical and endoscopic response or remission in patients with active CD on UST maintenance therapy. A multi-centre retrospective cohort study was performed. Adult patients (>18 years old) who received an IV re-induction dose of UST for either partial response or secondary LOR to UST, based on clinical, biochemical or endoscopic criteria, were identified at two Canadian academic centres. Post-reinduction, clinical remission was defined as an HBI < 5 off corticosteroids. Biochemical response and remission were defined as ≥ 50% decrease and normalisation, respectively, of faecal calprotectin (FCP) and/or CRP. Endoscopic remission was defined as a SES-CD score of < 3 and endoscopic response was defined as a decrease in SES-CD ≥ 50%. Adequate drug concentrations were defined as a UST level of ≥ 1 μg/ml. The primary outcome of interest was complete clinical, biochemical and endoscopic remission. Secondary outcomes included clinical remission, biomarker response, and safety. Twenty-eight patients (median age 35.5 years, 46% women) underwent IV reinduction between January 2017 and July 2018. The indication for re-induction was partial response in 43% (n = 12) and LOR in 57% (n = 16). The majority of patients (89%) received re-induction while receiving UST maintenance q 4 weeks. The median time to re-induction was 18.5 months (interquartile range [IQR]: 13.0–34.8). Clinical outcomes were assessed at a median of 14 weeks (IQR: 13–17) post re-induction. The primary outcome was achieved in 28.6% (n = 8). Clinical remission with biochemical response was achieved in 53.8% of patients (n = 14). Therapeutic drug monitoring for UST was performed in 10 patients prior to reinduction, and 18 patients post-reinduction. Pre-reinduction UST concentrations were ≥ 1 μg/ml (mean 3.8 ± 3.5 μg/ml) in 80%, compared with 100% of post-reinduction UST concentrations (mean 6.4 ± 4.2 μg/ml). The mean UST concentration post-reinduction was significantly higher in patients having achieved the primary outcome compared with those who did not (9.7 ± 4.1 vs. 4.8 ± 3.1 μg/ml, p = 0.01). No serious adverse events were reported following UST re-induction. Ustekinumab IV reinduction can be used safely to induce complete remission and response in patients with Crohn’s disease with partial response or losing response, even in the context of previously defined adequate UST drug concentrations. Further studies evaluating this strategy are warranted.

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