Real World Evidence Comparing Vedolizumab and Ustekinumab in Anti-TNF Experienced Patients With Crohn's Disease

Introduction: Many patients with Crohn’s disease (CD) lose response or become intolerant to anti-TNF therapy. Newer classes of biologics have demonstrated efficacy in anti-TNF experienced patients, but real-world comparative effectiveness studies are limited and have yielded conflicting results. We sought to compare the effectiveness and safety of ustekinumab to vedolizumab in a large, geographically diverse United States (U.S.) population of adult patients with CD previously treated with TNF inhibitors. Methods: We conducted a retrospective cohort study using longitudinal claims data from a large national U.S. insurance company (Anthem, Inc.). We identified CD patients initiating vedolizumab or ustekinumab with evidence of anti-TNF treatment in the prior 6 months. Our primary outcome was treatment persistence > 52 weeks. Select secondary outcomes included: 1) all-cause hospitalization; 2) hospitalization for CD with surgery; 3) hospitalization for CD without surgery, and 4) hospitalization for infection. Propensity score fine stratification was used to control for confounding by demographic and clinical characteristics and prior treatments at baseline. Results: We identified 885 new users of ustekinumab and 490 new users of vedolizumab who met criteria for our primary analysis. We observed no difference in treatment persistence [adjusted RR 1.09 (95% CI 0.95 -1.25)]; however, ustekinumab was associated with lower all-cause hospitalization (adjusted HR 0.73 [0.59-0.91]) and non-surgical CD hospitalizations (adjusted HR 0.58 [0.40-0.83]) (Figure). Ustekinumab initiators were also less likely to be hospitalized for infection (adjusted HR 0.56 [ 0.34-0.92]). Conclusion: This real-world comparative effectiveness study of anti-TNF experienced CD patients initiating vedolizumab or ustekinumab showed similar treatment persistence rates beyond 52 weeks, although secondary outcomes such as all-cause hospitalization, non-surgical CD hospitalizations, and hospitalizations for infection favored ustekinumab initiation. We therefore advocate for individualized decision making in this medically refractory population, considering patient preference, prior Anti-TNF experience and other factors such as cost and route of administration.Figure 1.: Incidence and Effect Estimates for Primary and Secondary Endpoints in New Users of Ustekinumab vs Vedolizumab