P103 Ustekinumab: medium-term outcomes from a uk multi-centre real-world cohort

Introduction Ustekinumab (UST) is effective at inducing and maintaining remission of Crohn’s disease (CD). However, real-world practice varies regarding concomitant immunomodulator (IM) use and dosing regimens, with scarce data on factors predicting outcomes. We present a UK real-world (RW), multi-centre cohort. Methods A retrospective study was conducted of adult patients with CD initiated on UST between October 2016–18 at two tertiary London centres. Clinical endpoints were (i) remission (Harvey Bradshaw Index (HBI) ≤4), (ii) response, (reduction in HBI of ≥3 or sustained HBI≤4 points), at 3, 6 and 12 months. Biological endpoints were remission & response (CRP 5 mg/L, and 50% reduction in CRP respectively). Predictable variables were assessed by multivariate analysis using logistic regression. Results The baseline characteristics of 120 patients were: 59 (49%) male; median age 34 yrs (IQR 26–44); median disease duration 12 yrs (7–17); 80 (66%) ileocolonic disease; 88 (73%) stricturing or penetrating disease; 61 (51%) perianal disease. 117 (98%) were biologic exposed, 34 (28%) had failed ≥3 biologics and 67 (56%) had required previous surgery. 15 (13%) patients were on steroids at baseline. Mean HBI was 5 (sd 5, n=112), CRP 15 (sd 18, n=117) and faecal calprotectin 431 (sd 808, n=46). Clinical and biological endpoints are shown in figure 1. At 6 and 12 months, 79 (74%) and 68 (78%) patients were on escalated 8 weekly dosing. Dosing regimen did not impact outcomes. UST discontinuation occurred in 2 (1.7%), 13 (10.8%) and 33 (27.5%) patients by 3, 6 & 12 months. Reasons included (n): primary non-response (23), loss of response (9), sub-optimal response (4) and side effects (4). Adverse events occurred in 23 (19%) patients, including 12 patients requiring surgical intervention for progressive disease. Concomitant IM were prescribed in 56 (47%) patients at baseline and continued in 47 (39%) and 38 (32%) at 6 and 12 months, respectively. Concomitant use did not impact outcomes at any timepoint, nor affect median treatment persistence with UST. Prior anti-TNF exposure was a negative predictor of clinical remission at one year, OR 0.32 (95% CI 0.12–0.81, p≤0.02), but there was no association with disease location, phenotype, presence of perianal disease or those with a smoking history. Conclusions Ustekinumab is effective in the treatment of moderate-severe CD in a treatment refractory RW cohort. In keeping with trial data, prior anti-TNF exposure was a negative predictor of remission and concomitant IM use did not alter clinical or biological outcomes.