Vedolizumab vs ustekinumab: Which holds greater advantage for patients with CD?

Treatment with either vedolizumab or ustekinumab delivers significant and meaningful benefits to patients with Crohn’s disease (CD), but each has its distinct therapeutic profile with complementary advantages, reports a real-world study presented at CCC 2026.

“Vedolizumab may be preferred for patients at high risk for surgical complications but carries increased infectious and haematologic risks,” said lead study author Dr M Kenan Rahima, chief internal medicine resident at TriHealth, US. On the other hand, “ustekinumab demonstrates superior systemic inflammation control with a potentially safer profile.”

Rahima and his team conducted this retrospective cohort study using the TriNetX US Collaborative Network, which covers 69 healthcare organizations. They included adult patients with CD who initiated vedolizumab (n=4,697) or ustekinumab (n=10,771) with ≥3-month washout from aminosalicylates.

Participants underwent propensity score matching (1:1) to balance demographics, comorbidities, and prior medication exposure, resulting in 4,567 matched pairs. Rahima and colleagues assessed the primary and secondary outcomes over 3 years using Kaplan-Meier survival analysis, hazard ratios (HRs), and 95 percent confidence intervals (CIs) with log-rank testing.

Procedural outcomes

Patients with CD who received vedolizumab had fewer outpatient visits (HR, 0.50, 95 percent CI, 0.40‒0.63; p<0.001), stricturoplasty/dilation procedures (HR, 0.62, 95 percent CI, 0.43‒0.87; p=0.006), fistulectomy (HR, 0.60, 95 percent CI, 0.37‒0.97; p=0.036), and reduced perianal abscess drainage (HR, 0.58, 95 percent CI, 0.35‒0.98; p=0.038) than those treated with ustekinumab. [Inflamm Bowel Dis 2026;doi:10.1093/ibd/izag006.017]

However, the use of vedolizumab vs ustekinumab resulted in a significantly higher all-cause mortality (2.4 percent vs 1.6 percent; HR, 1.47, 95 percent CI, 1.09‒1.97; p=0.010).

Vedolizumab-treated patients were also at greater risk of developing thrombocytopenia (2.0 percent vs 1.1 percent; HR, 1.83, 95 percent CI, 1.28‒2.61; p=0.001), sepsis (3.2 percent vs 2.3 percent; HR, 1.36, 95 percent CI, 1.05‒1.75; p=0.019), pneumonia (2.9 percent vs 2.0 percent; HR, 1.41, 95 percent CI, 1.07‒1.85; p=0.013), and Clostridioides difficile infection (1.7 percent vs 1.1 percent; HR, 1.50, 95 percent CI, 1.04‒2.16; p=0.028) than those who received ustekinumab.

No significant between-group differences were observed on hospitalization rates, emergency visits, and inflammatory bowel disease surgery.

Inflammation control

Furthermore, ustekinumab was superior to vedolizumab in terms of systemic inflammation control, as shown by the lower rates of elevated C-reactive protein ≥10 mg/L (10.8 percent vs 12.9 percent; HR, 1.17, 95 percent CI, 1.01‒1.35; p=0.033) and hypoalbuminaemia (9.6 percent vs 12.1 percent; HR, 1.24, 95 percent CI, 1.07‒1.44; p=0.005).

In contrast, vedolizumab demonstrated better faecal calprotectin normalization <150 μg/g than ustekinumab (11.6 percent vs 10.3 percent; HR, 0.85, 95 percent CI, 0.75‒0.97; p=0.017), indicating superior local intestinal inflammation control.

“These real-world findings support individualized treatment selection based on patient-specific risk factors and warrant confirmatory prospective head-to-head trials,” Rahima said.

Vedolizumab is an anti-integrin agent, while ustekinumab is an anti-interleukin-12/23 monoclonal antibody. Both agents are used as conventional biologics for the treatment of moderate-to-severe CD.

“Despite increasing utilization, real-world comparative effectiveness data remain limited, particularly regarding long-term clinical outcomes, safety events, and biomarker normalization patterns,” according to Rahima and colleagues.