Indicators of Suboptimal Treatment Among Patients With Crohn's Disease Treated With Ustekinumab or Risankizumab and Treatment Journey Among Ustekinumab Discontinuers in the United States

Background and Aims Patients with Crohn's disease (CD) may experience suboptimal response to advanced therapies (ATs), including interleukin (IL)‐12/23 inhibitor ustekinumab and IL‐23 inhibitor risankizumab. In an evolving treatment landscape, this study evaluated indicators of suboptimal treatment with these agents. Methods This retrospective study used medical and pharmacy claims from the Komodo Research Data database (06/17/2022–11/30/2023). Adults with CD who initiated ustekinumab or risankizumab (index date) with ≥ 12 months of baseline coverage and without baseline CD‐indicated AT use were included. Baseline characteristics were balanced using inverse probability of treatment weights. The primary outcome was a composite indicator of suboptimal treatment comprising CD‐related surgery, CD‐related inpatient or emergency department (i.e., acute care) visits, AT switch, augmentation with corticosteroids, 5‐aminosalicylic acid or immunomodulators, or dose escalation. Time to event from maintenance phase was analyzed using Kaplan–Meier and Cox proportional hazards models. Results A total of 2218 patients initiated ustekinumab and 858 initiated risankizumab; baseline characteristics were balanced for ustekinumab versus risankizumab (mean age: 44.9 vs. 44.4 years; female: 53.3% vs. 53.6%; corticosteroid use: 63.8% vs. 64.7%). After 6 months of maintenance, the risk of suboptimal treatment was similar (37.0% ustekinumab vs. 35.2% risankizumab; hazard ratio [HR] = 1.13; p = 0.121), including risk of CD‐related surgery (HR = 0.63; p = 0.081), switch to a new AT (HR = 1.35; p = 0.368), and corticosteroid augmentation (HR = 1.00; p = 0.999). The risk of CD‐related acute care was significantly higher on risankizumab (HR = 0.70; p = 0.013). Conclusions Over one‐third of AT‐naïve patients with CD experienced suboptimal treatment after 6 months of ustekinumab or risankizumab maintenance therapy. Similar risks between cohorts highlight potential unmet needs with these agents. Future work should focus on more recently approved IL‐23 agents, including guselkumab and mirikizumab.