Real-World Clinical Effectiveness and Safety of Vedolizumab and Ustekinumab in Bio-naive Patients With Complex or Noncomplex Crohn’s Disease: Results From the EVOLVE Expansion Study

Real-world outcomes in patients with CD treated with vedolizumab or ustekinumab were evaluated in 2 retrospective, multicenter, observational studies that assessed patient chart data from the EVOLVE Expansion trial.^1-3 The retrospective analyses included patients with either complex or noncomplex CD.^4,5 The Evolve Expansion trial enrolled biologic-naive patients with previously diagnosed CD in whom treatment with ustekinumab or vedolizumab was initiated during the eligibility period in Australia, Belgium, or Switzerland. Complex CD was defined as the presence of 1 or more of the following conditions: active fistula at treatment initiation, any prior CD-related surgery since diagnosis, and any CD-related hospitalization within 12 months before the initiation of treatment. The main study endpoints were clinical outcomes, treatment persistence, and safety. A series of hierarchical algorithms was used to assess clinical outcomes, including clinical response, clinical remission, and mucosal healing.⁶

The patients with complex CD whose data were analyzed included 97 treated with ustekinumab and 99 treated with vedolizumab.⁴ After adjustment by inverse probability to treatment weighting, no significant differences in baseline characteristics were found between the 2 treatment cohorts. In the 2 cohorts, the median duration of disease was 9.2 to 9.7 months, and 51% to 52% of the patients had ileal disease without upper tract disease. Disease behavior at baseline was nonstricturing and nonpenetrating in 47% to 49% of patients and was stricturing in 29% to 35% of patients. Most of the patients had moderate disease (68%-70%); severe disease was noted in 16% to 17%. Characteristics of complex CD included fistula before the initiation of treatment (27%-28%), CD-related surgeries since diagnosis (67%-72%), and CD-related hospitalizations in the 12 months before the initiation of treatment (53%).

ABSTRACT SUMMARY Association of Non-switched Memory B-cell (MBC) Levels With Ozanimod (OZA) Efficacy in Patients (Pts) With Moderately to Severely Active Crohn’s Disease (CD): Results From the Phase 2 STEPSTONE Study

An exploratory analysis of data from the STEPSTONE study evaluated the association between circulating levels of specific lymphocyte populations and efficacy outcomes after 12 weeks of induction therapy with ozanimod (Abstract P3572). Among 52 patients, the most consistent results were observed for levels of non-switched memory B cells at baseline. Patients with higher vs lower levels of non-switched memory B cells at baseline were more likely to achieve an endoscopic response (P=.0046), endoscopic remission (P=.0054), remission based on the global Geboes histological score (P=.0046), and mucosal healing (P=.0039). Reductions in levels of non-switched memory B cells by week 12 were associated with reduced clinical and histologic disease activity.

The analysis generally showed no significant differences between the outcomes of patients with complex CD treated with ustekinumab vs vedolizumab. After 36 months of treatment, the weighted cumulative rate of response was 79.4% with ustekinumab or vedolizumab (P=.78), and the weighted cumulative rate of clinical remission was 82.9% to 83.1% (P=.58). The rate of weighted cumulative mucosal healing was 78.7% with ustekinumab vs 90.1% with vedolizumab (P=.12), and the rate of weighted cumulative treatment persistence was 70.9% with ustekinumab vs 73.9% with vedolizumab (P=.83). Similarly, after 12 or 24 months of follow-up, no significant differences in clinical outcomes were observed. During 36 months of follow-up, rates of serious infections were low (incidence rate of first occurrence per 100 patient-years [IRFO₁₀₀], 0.0 with ustekinumab vs 1.3 with vedolizumab; hazard ratio [HR], not estimable). With ustekinumab vs vedolizumab, the IRFO₁₀₀ was 7.7 vs 5.7 for serious AEs (HR, 0.72; 95% CI, 0.32-1.64; P=.44), 14.2 vs 11.5 for CD exacerbations (HR, 0.89; 95% CI, 0.47-1.67; P=.71), 2.3 vs 6.2 for CD-related surgeries (HR, 3.20; 95% CI, 0.91-11.28; P=.07), and 13.0 vs 9.0 for CD-related hospitalizations (HR, 0.83; 95% CI, 0.43-1.59; P=.57) (Figure 6).

Figure 6.

Risk of serious AEs, CD exacerbations, CD-related surgeries, and CD-related hospitalizations in biologic-naive patients with complex CD treated with vedolizumab vs ustekinumab during 36 months of follow-up from the EVOLVE expansion study.

AE, adverse event; CD, Crohn’s disease; IRR, incidence rate ratio; HR, hazard ratio; NE, nonestimable.

Adapted from Ferrante et al. Abstract 71. Presented at: ACG 2023; October 20-25, 2023; Vancouver, British Columbia, Canada.⁴

A related study retrospectively examined real-world data from patients with noncomplex CD in the EVOLVE study.⁵ Patients with noncomplex CD were those who did not have active fistula at baseline, had no prior CD-related surgery since diagnosis, and had no CD-related hospitalization before baseline. This study also used the hierarchical algorithms for clinical assessment, and inverse probability of treatment weighting was used to adjust patient data at baseline. The study included 218 patients treated with ustekinumab and 209 treated with vedolizumab. Patient baseline characteristics were similar in the 2 treatment cohorts. Among the patients with non-complex CD, after 36 months of follow-up, ustekinumab and vedolizumab yielded rates of clinical and safety endpoints that did not differ significantly on the basis of clinical response, clinical remission, mucosal healing, treatment persistence, serious AEs, serious infections, CD exacerbations, CD-related surgeries, and CD-related hospitalizations (P>.05 for each).