Real World Evidence on the effectiveness of ustekinumab in Crohn's Disease: Induction phase results from the prospective, observational RUN-CD Study

Abstract Background Prospective, observational real world studies on the effectiveness and safety of ustekinumab (UST) in Crohn’s disease (CD) are required in addition to RCTs, usually confined to selected patients, which may not represent special treatment patterns and everyday clinical practice. The aim of the present 3-year RUN-CD study was to investigate the induction phase effectiveness of UST vs. other biologics (OB) in CD in terms of clinical and steroid-free remission at week 16. To the best of our knowledge, RUN-CD is currently the largest prospective real world evidence (RWE) study with UST in CD using propensity score adjustment. Methods Between 2017–2020, 901 CD-patients starting a new therapy with UST or OB, were enrolled in 44 IBD-experienced centers across Germany. After exclusion of missing outcomes, the final sample consisted of 657 patients. Clinical remission (HBI ≤ 4), and steroid-free remission (HBI ≤ 4 and no systemic use of steroids or budesonide during the last 8 weeks) were considered as outcomes at week 16. To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 339 UST (naïve: 34) and 318 OB CD-patients were included (ADA: 50.3%, IFX: 37.4%, VDZ: 12.3%) (naïve: 203). PS removed systematic differences between both groups (30.8% smokers, 15.1% perianal disease, 36.2% surgical resection, 40.5% EIM). The effectiveness of UST for clinical and steroid-free remission was comparable to that of OB at week 16. Besides, in bio-naïve patients, clinical remission was numerically, though not significantly, higher in UST vs OB (Table 1). Similar results were observed in the bio-experienced UST vs. OB groups [remission: 59.3% vs 55.4%; OR: 1.17 (0.73–1.90)]. For both the remission rates were higher in the bio-naïve than in the bio-experienced groups (p<0.05 for both). Conclusion In this prospective RUN-CD study, with propensity score weighted groups, UST showed similar induction effectiveness in comparison with OB therapies. Remarkably higher remission rates were observed in this RWE study than in prior RCTs. An additional favorable safety profile supports consideration of UST as a first-line targeted therapy for CD.