Effectiveness and safety of ustekinumab in Crohn's disease: short and long-term results of a multi-refractory cohort

Abstract Background To evaluate the short and long-term effectiveness and safety of ustekinumab (UST) in a real-world multirefractory Crohn’s disease (CD) cohort. Methods An observational, retrospective and single-center study of CD patients treated with UST since June, 2017, with at least, 16 weeks of treatment. All patients were identified in the ENEIDA Registry. Demographic, disease, and outcome variables were collected. Clinical remission and response (measured by the physician global assessment and Harvey Bradshaw Index (HBI) score) as well as biological response (measured by C-reactive protein (CRP) and fecal calprotectin) were evaluated at weeks, 16, 26, 52 and at the end of the follow-up. Kaplan-Meier survival curves were performed to analyze drug persistence and multivariate analysis to identify predictors of response. Treatment-related adverse events were assessed. Results 64 patients included, mean age of, 49 years (35–60), 56.2% men and CD duration of, 15.5 years (8–22)., 53% had ileocolic involvement and, 59% stricturing and/or penetrating disease., 40% presented perianal disease, 35% active smoking and, 33% patients had extraintestinal manifestations., 92.2% had prior failure to biologics (44% failed at, 1 and, 48.5% failed ³2) and, 9.4% had failed to vedolizumab., 57.8% required prior surgery for IBD., 40.6% initiated UST for treatment of postoperative recurrence. Baseline clinical activity was present in, 87.5% patients (60% moderate-severe activity). Rates of clinical remission, response and no response were, respectively, 40.7%, 47.5% and, 12% at week, 16;, 56.8%, 32.8% and, 10.3% at week, 26;, 60%, 30% y, 10% at week, 52. At the end of the follow-up, more than, 2/3 of patients (76.3%) had clinical response or remission (figure 1). Overall, a significant reduction of HBI score was observed from baseline to week, 16 and maintained at W26 and W52 (figure 2). Likewise, a biological response was observed with a significant reduction of CRP (baseline of, 26.7 mg/dL) at different times of evaluation (figure 3)., 74.9% continued with UST for up to three years (figure 4). In the multivariate analysis, the only independent factor associated with non-response was previous therapy with vedolizumab (OR:, 0.055 [IC95%:, 0.005–0.551], p=0.001). The safety profile was favorable; only, 2 patients (3.1%) stopped the drug due to side effects (arthralgias and bladder neoplasia). Fig, 1. Remission, response, and no response rates. Fig, 2. Evolution of HBI score from baseline to W52. Fig, 3. Evolution of CRP from baseline to W52. Fig, 4. Persistence of ustekinumab during the follow-up period. Conclusion UST is effective and safe in a real-life refractory CD cohort, with a persistence of the drug of, 75% at, 3 years. Previous vedolizumab therapy is associated with UST treatment failure.