S7 Crohn’s Disease: What to Do After Antitumour Necrosis Factor-α Therapy Fails?

Abstract

Background: Ustekinumab and vedolizumab are commonly used for the treatment of Crohn’s disease (CD) after antitumour necrosis factor-α (anti-TNF-α) therapy fails. The optimal choice is still debated. However, some evidence suggests the superiority of Ustekinumab. The aim of this study was to compare the effectiveness of ustekinumab and vedolizumab as second line therapy in CD patients. Methods: Retrospective single-center study including patients with CD who started on ustekinumab or vedolizumab, after failure of or intolerance to anti-TNF-α therapy, between January 2017 and December 2021. Clinical response was defined as a reduction in Harvey-Bradshaw index (HBI) of ≥3 points comparing with initial value or HBI<5 points if initial HBI≥7 points and clinical remission as HBI≤4 points. Biochemical outcomes were erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and faecal calprotectin, 6 and 12 months after initiating treatment. Objective response at 12 months was assessed by endoscopic studies, defined by improvement of mucosal inflammation and absence of deep ulcerations, or through imaging, defined as improvement in bowel wall thickness, inflammatory fat, mural blood flow and hyper-enhancement. Results: Totally, 52 CD patients were included, 37 patients were treated with ustekinumab (71.2%) and 15 with vedolizumab (28.8%). Among patients with ustekinumab, 26 were female, with a mean age at beginning of treatment of 41.05 ± 15.04 years. Considering the Montreal classification, 14 ustekinumab patients had ileal disease, 2 had colonic and 21 ileocolonic disease; 10 patients had nonstricturing, nonpenetrating disease, 15 had stricturing and 12 penetrating disease. Among patients with vedolizumab, 10 were female, with a mean age at beginning of treatment of 36.47 ± 12.87 years. According to Montreal classification, 3 vedolizumab patients had ileal disease and 12 had ileocolonic disease; 3 patients had nonstricturing, nonpenetrating disease, 8 had stricturing and 4 penetrating disease. No statistically significant differences were found between both groups regarding sex (P = 0.216), age (P = 0.305), disease behavior (P = 0.787) or location (ileal or ileocolonic) (P = 0.171). At 6 months, clinical response was observed in 15 ustekinumab patients (40.5%) and 9 vedolizumab patients (60.0%), without statistically significant differences (P = 0.202). Clinical remission occurred in 14 ustekinumab patients (37.8%) and 6 vedolizumab patients (40.0%), without statistically significant differences (P = 0.885). Furthermore, no statistically significant differences were found in biochemical parameters at 6 months, between the 2 groups. At 12 months, clinical response and remission was similar between both groups. Moreover, all biochemical parameters evaluated decreased in both groups, although without statistically significant differences, ESR (ustekinumab median -4.5 vs vedolizumab median -2.0, P = 0.393), CRP (ustekinumab median -2.35 vs vedolizumab median -2.10, P = 0.878), and faecal calprotectin (ustekinumab mean -329.5 vs vedolizumab mean -52.4, P = 0.077). An objective response at 12 months was observed in 58.8% ustekinumab patients and 50.0% vedolizumab patients, with no statistically significant differences (P = 0.149). Conclusion(s): In CD patients after anti-TNF-α therapy failure, both ustekinumab and vedolizumab showed clinical and biochemical improvements. After 1 year of treatment, about half of patients from both groups had positive objective response, assessed by endoscopic or imaging studies.