Clinical, Endoscopic, and Radiological Effectiveness of Ustekinumab in Bio-naive Versus Bio-experienced Patients With Crohn's Disease: Real-world Experience From a Large Canadian Center

Lay Summary In this large real-world study of patients with Crohn's Disease treated with ustekinumab, we observed high rates of clinical, endoscopic, radiological, and biochemical response and remission rates. Effectiveness was greater in bio-naive compared with bio-experienced patients. Introduction With the expanding therapeutic armamentarium for inflammatory bowel disease (IBD), real-world data may help inform drug positioning. We assessed clinical, endoscopic, imaging, and biochemical response/remission outcomes in patients with Crohn's disease (CD) treated with ustekinumab in a large Canadian IBD center. Methods A retrospective cohort study of CD patients was treated with ustekinumab. Clinical, endoscopic, radiological, and biochemical response and remission outcomes were stratified by prior biologic exposure status. Hazard ratios for biologic exposure status were estimated using Cox proportional hazard models and subgroup-specific incidence rates for healing. Results A total of 231 patients (55.9% female, median 45.8 years) were identified as receiving ustekinumab during the study period, with 2 patients subsequently excluded (N = 229). Of these patients, 79.0% (181 of 229) were bio-experienced, with 38.7% (70 of 181) having failed 1 biologic and 61.3% (111 of 181) having failed >= 2 biologics. At 3 months of follow-up after induction, clinical remission (Harvey-Bradshaw Index <= 4) was achieved by 59.1% (62 of 105) of bio-experienced patients and 79.4% (27 of 34) of bio-naive patients (relative risk [RR], 1.34; 95% CI, 1.06-1.70; P = .013). Endoscopic remission (absence of mucosal ulcers) was achieved in 37.9% (33 of 87) cases. Rate of endoscopic healing (either endoscopic response or remission) per 1000 person-months was 72.7 (95% CI, 42.4-125.1) and 50.2 (37.9-66.4); and the median time to endoscopic response was 8.4 months (95% CI, 6.4-9.8) and 15.4 months (95% CI, 10.3-17.9) in bio-naive vs bio-experienced patients, respectively. Imaging response/remission and steroid-free remission rates were higher in bio-naive patients. Conclusion In this large real-world cohort of CD patients with complex phenotypes and high rates of prior biologic exposure, we observed that ustekinumab was effective and safe with higher rates of improvement in bio-naive subjects across a range of end points.