PTH-085 Ustekinumab for refractory Crohn’s disease (CD) in adolescents: experience from two UK IBD centres

Introduction There is an increasing incidence of CD in adolescents and young persons (AYP). Whilst anti-TNF use in AYP is well established, little is reported on the efficacy and safety of vedolizumab. We describe our multicentre experience. Methods Data was retrospectively collected on 14–23yr olds starting vedolizumab at University College London Hospital (UCLH) and The Royal London Hospital (RLH) from June 2015–18. Endpoints were: clinical (i) response (reduction in Harvey Bradshaw Index (HBI) of ≥3 or sustained HBI ≤4 points) (ii) remission (HBI ≤4 points), and biological (i) response (50% reduction in CRP) and (ii) remission (CRP 5 mg/L) at weeks 14, 30 and 54. Results Table 1 summarises the baseline characteristics of 35 AYP commenced on vedolizumab. 34 patients were included in the analysis at week 54. 28 patients who received induction treatment commenced 8 weekly maintenance infusions at week 14. Overall 28 patients had stopped treatment before week 54 (including 14 for primary non-response and 7 for loss of response). The median time to stopping vedolizumab was 7 months (IQR 4–29, 95%CI 5–10). Analysing paired data only, mean (sd) HBI showed a downward trend from baseline to week 14, and was significantly decreased from baseline (4.5(4.3)) to week 22 (2.5(2.9), n=20, p=0.03), to week 30 (2.4(2.9), n=16, p=0.02), and week 54 (2.0(3.4), n=9, p=0.02). Mean (s.d.) CRP (mg/L) showed a downward trend from baseline to weeks 14 and 22, and was significantly decreased from baseline (17.8(16.9)) to week 30 (8.3(7.2), n=16, p=0.04). This trend was sustained but did not achieve significance at week 54 (7(6.0), n=9, p=0.2). Mean (sd) weight (kg) showed an upward trend from baseline to weeks 14 and 22 and was significantly increased from baseline (61.5(11.7)) to week 30 (65.6(12.4), n=13, p=0.004), and week 54 (66.3(15.5), n=9, p=0.006). At weeks 14, 30 and 54, the rates of clinical (i) response and (ii) remission were (i) 56, 37 and 24% respectively and (ii) 47, 37, 24% respectively. At weeks, 14, 30 and 54, the rates of biological (i) response and (ii) remission were (i) 29, 25, and 11% respectively and (ii) 10, 15 and 9% respectively. Conclusions We report on the use of vedolizumab in AYP at 2 tertiary IBD centres. Our experience suggests that whilst medium term (6 month) effectiveness in an anti-TNF experienced cohort is comparable with outcomes from adult and trial data, this is not sustained to a year. This may be reflective of a cohort of patients with early onset CD with a more aggressive phenotype and coexisting perianal disease. Further studies may help identify which adolescents would most benefit from vedolizumab. This is of growing importance in the face of an expanding therapeutic armamentarium in CD.