Inadequate Efficacy of Biologics for Treating Proximal Ileal Lesions in Crohn's Disease: A Prospective Multicenter Study

Background & Aims: Although biologic therapy has revolutionized the treatment of Crohn's disease (CD), surgery remains unavoidable in cases involving ileal complications. We aimed to evaluate the efficacy of biologics on proximal ileal lesions using balloon-assisted enteroscopy (BAE). Methods: This open-label multicenter prospective study was conducted at tertiary referral centers in Japan. We enrolled 253 patients with active ileal CD who were treated with biologics (infliximab/adalimumab/ustekinumab/vedolizumab). BAE was performed at week 0 and week 26, and endoscopic findings were centrally assessed. We evaluated the rate of endoscopic remission (defined as having a maximum modified Simple Endoscopic Score for Crohn's disease <4) at week 26 and patient prognosis (CD-related hospitalization and surgery). Results: At baseline, 74 patients (29.2%) had proximal ileal ulcerations without terminal ileal ulcerations. The second BAE showed that endoscopic remission was achieved in 91 patients (36.0%). Of the patients with complete ulcer healing of the terminal ileum, 28.6% (22/77) had residual ulcers in the proximal ileum. The rate of endoscopic remission in the proximal ileum (50.9%) was relatively lower compared with the colon (63.4%) and terminal ileum (56.7%), a trend consistently observed across all treatment agents. After a median follow-up of 134 weeks, residual ulcerations in the proximal ileum were associated with a poorer prognosis (P = .0126 for hospitalization and P = .0014 for surgery). Conclusions: A substantial proportion of patients with CD exhibited ulcerations in the proximal ileum, which correlated with a poorer prognosis. These lesions proved challenging to heal, regardless of the type of biologic used.