Therapeutic sequencing in inflammatory bowel disease: Determining the optimal position of vedolizumab for long-term Crohn's disease control using real-world evidence

Background: Several biologics are available for the treatment of moderate to severe Crohn's disease, but data to optimize their use are scarce. Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking monoclonal antibody that was approved in 2014 for the treatment of moderate to severe Crohn's disease. Based on real-world evidence, a model was developed to examine the effect of VDZ's position in the treatment sequence on clinical outcomes. Objective: The aim of this study was to develop a model using real-world data to investigate how the positioning of VDZ in a sequence of biologic therapies for CD affects clinical effectiveness outcomes of quality-adjusted life-years (QALYS), patient-reported disease activity, and surgery rates. Methods: A semi-Markov sequential model was developed to identify the optimal position of VDZ in a treatment sequence that included corticosteroids (CS), two biologics, and best supportive care (BSC). Using real-world data, three sequences were compared: VDZ as first (position), second, and last biologic (with anti-tumor necrosis factor alpha agents adalimumab (ADA) and infliximab (IFX) and the anti-interleukin-12 and -23 agent ustekinumab (UST) as alternative biologic treatments). Published real-world evidence informed model inputs. Vedolizumab sequences were compared and ranked based on QALYS, patient-reported outcomes from Crohn's disease activity index scores, or proportion of patients undergoing surgery by the 10-year time horizon for model simulation. Sensitivity analyses were used to evaluate the impact of model input uncertainty. Results: Vedolizumab as the first biologic was the optimal position for this treatment according to all criteria, including yielding the highest QALYs (5.09) versus VDZ in second (4.97) and third (4.96) biologic sequence positions in sequences containing CS, anti-TNF alpha (aggregated data), UST, and BSC; 1780/2000 (89%) probabilistic simulations. In sequences containing ADA, VDZ, and UST biologics, ADA and VDZ in the first-line biologic position yielded QALYs of 5.09 versus 5.07, respectively. Adalimumab as the first biologic was best for clinical remission. Conclusions: This simulation model using real-world evidence indicates that positioning VDZ or ADA as the first biologic is likely to lead to improved long-term patient outcomes when compared to administering these treatments later or starting with IFX monotherapy.