DOP003 Ustekinumab induces clinical and biological remission in biologic refractory Crohn’s disease patients: A real-world belgian cohort study

Abstract

Background: Ustekinumab (UST), a fully humanized IgG1 monoclonal antibody targeting IL12/23p40, was recently approved for moderate to severe Crohn's disease (CD). We report real world short-term efficacy data in a Belgian cohort (14 centres) with prior exposure to both anti-TNF and vedolizumab and correlate outcome with week 8 UST serum levels. Methods: Prospectively collected data were retrospectively analysed according intention-to-treat. Patients received IV UST (induction) and 90 mg SC q8 weeks from week 8. Primary endpoints were clinical response/remission at week 8 and 16. Clinical response/remission were defined as a reduction in Harvey Bradshaw Index (HBI) of ≥3 and a HBI ≤4 respectively. Biological response/remission were defined as 50% drop of C-reactive protein (CRP) and CRP <5mg/L respectively if CRP≥5mg/l at baseline. Serum UST samples were available in 94 patients at week 8 and were measured with an ELISA developed by KU Leuven with the same specificity, selectivity, accuracy and precision as the J&J assay. Paired analysis was performed for faecal calprotectin (fCal) when values at baseline and week 8 (=60) and week 16 (n=33) were available. Results: Demographic and baseline data of the study population of 157 (142 reached week 16) patients are presented in Table 1. At week 8, clinical response and remission were achieved in 56.7% (89/157) and 27.4% (43/157) of patients, respectively. At week 16, clinical response and remission was achieved in 53.5% (76/142) and 31.7% (45/142). Biological response and remission was achieved in 25.8% (31/120) and 8.3% (10/120) respectively at week 8 and in 23.8% (25/105) and 10.5% (11/105) at week 16 (Figure1). CRP significantly decreased from baseline (14.7 mg/L, IQR [8.8-27.7]) to 6.2 mg/L at week 8 (IQR [2.85-11.85], p<0.0001) and 6.6 mg/L (IQR [2.2-14.9] at week 16, p<0.0001). In subset with available paired samples, a 50% drop in fCal was observed in 33% (20/60) and in 39.4% (13/33) of patients at week 8 and 16. Week 8 UST levels were not significantly associated with (short-term) clinical response (p=0.15). However, a significant inverse correlation was seen between UST levels and CRP at week 8 (r=-0,322; p=0.002). At induction, 33.3% of patients (47/141) experienced arthralgia (excluding patients with ankylosing spondylitis (n=16)), disappearing in 25.5% and 34% of them at week 8 and 16 respectively. By week 16 only 3.2% of patients (5/157) had reported side effects (Clostridium and CMV infection, intense myalgia, pregnancy, deep venous thrombosis) and 5.7% of patients (9/157) required surgery associated to CD. Conclusions: UST is effective in inducing short term clinical response and remission in this highly refractory CD cohort, including a significant reduction in CRP levels and calprotectin (when available). UST levels at week 8 inversely correlate with CRP but not with short-term outcome [Table Presented] [Figure Presented]