Phase 3 KEPLER trial shows vedolizumab remission benefit in pediatric ulcerative colitis

Intravenous vedolizumab (Entyvio; Takeda) achieved clinical remission in nearly half of pediatric patients with moderate to severe ulcerative colitis (UC) at 1 year, according to results from the phase 3 KEPLER trial (NCT04779307) presented at the 21st Congress of the European Crohn’s and Colitis Organisation and supported by new clinical insights from investigators and study authors.^1,2

UC in pediatric populations remains a therapeutic challenge, with limited approved options and often more aggressive disease than in adults. Ninfa Candela, MD, executive medical director of clinical development at Takeda and coauthor of the KEPLER abstract, emphasized that unmet need remains significant in this population.

“Children and adolescents with ulcerative colitis (UC) typically have more extensive inflammation, more intense symptoms, and faster disease progression than adults,” Candela said. “Even though cases of pediatric UC are rising around the world, it remains an area with surprisingly limited treatment options approved for use by health authorities, and patients often have to cycle through multiple therapies.”

Clinical remission achieved in nearly half of pediatric patients at 1 year

The KEPLER phase 3 trial evaluated intravenous vedolizumab in children and adolescents aged 2 to 17 years with moderate to severe UC who had an inadequate response to conventional therapies, including corticosteroids, immunomodulators, and tumor necrosis factor (TNF) antagonists.

The study enrolled 120 treated patients, with 93 randomly assigned to maintenance dosing after demonstrating a clinical response during the induction phase. The primary end point—clinical remission at week 54—was achieved by 47.3% of patients in the maintenance population. Secondary end points included remission at week 14, achieved by 34.7% of patients, and sustained remission at weeks 14 and 54, observed in 29.0%.

Candela noted that these outcomes should be interpreted within the context of a population with significant prior treatment failure.

“The week 54 remission (primary end point) rate of more than 47% is meaningful clinically, especially if we consider the study population,” she said. “This was a moderate to severe pediatric UC population who had already failed or lost response to conventional therapies and/or anti-TNF agents.”

She added that durable remission is particularly important in pediatric disease management.

“In pediatric UC, it is important to maintain remission over time, and the week 54 remission rate observed in the KEPLER trial reflects durable disease control,” Candela said.

Exposure-driven dosing strategy achieved consistent drug levels across age and weight groups

The KEPLER trial used a weight-tiered dosing strategy to achieve consistent therapeutic exposure across a broad pediatric age and weight range. Patients were stratified into weight-based dosing groups to ensure comparable vedolizumab exposure levels to those demonstrated to be effective and safe in adult populations.

Candela explained that the dosing design was informed by prior pediatric pharmacologic research.

“The dosing strategy was exposure driven, based on a previous, successful phase 2 trial,” she said. “The goal in KEPLER was to ensure that all children achieved vedolizumab drug exposures comparable to those associated with efficacy and safety in adults.”

She added that pharmacokinetic findings supported this approach.

“The pharmacokinetic data support that this weight-tiered approach delivers predictable, consistent vedolizumab levels from toddlers through adolescents,” Candela said.

Efficacy observed in patients with prior biologic or corticosteroid exposure

Treatment sequencing is a key concern in pediatric UC, particularly for patients who have failed biologic therapy or remain corticosteroid-dependent. The KEPLER trial demonstrated efficacy across multiple treatment-experienced subgroups, including those with prior TNF antagonist exposure.

Candela highlighted the relevance of these findings for clinical practice.

“In the KEPLER trial, vedolizumab demonstrated meaningful efficacy in patients who had prior exposure to anti-TNF therapy as well as in those with a history of corticosteroid use,” she said. “Additionally, this benefit was durable, extending through 1 year of maintenance therapy.”

These results suggest vedolizumab may offer a potential treatment option for pediatric patients with limited remaining therapeutic alternatives.

Safety profile consistent with adult data and no new safety signals identified

Safety findings from the KEPLER trial were consistent with the established safety profile of vedolizumab, with no new safety signals identified. Treatment-emergent adverse events occurred in most patients, with a smaller proportion considered treatment related, and discontinuations were uncommon.

Candela emphasized that safety findings were reassuring.

“With that perspective and looking at the KEPLER results, what stood out to me was the consistency of the overall safety profile and the safety profile over time—especially given the age range of the patients and the long duration of follow-up,” she said.

She added that most adverse events reflected either underlying disease or common pediatric conditions.

“Most [treatment-emergent adverse effects] were mild to moderate and reflected either underlying disease activity or common pediatric infections,” Candela said. “Additionally, there was no signal suggesting an increased risk of serious or opportunistic infections and no evidence of systemic immune suppression.”

Immunogenicity findings were also consistent with adult studies. “The incidence of anti-vedolizumab antibodies was low, consistent with what we see in adults, and neutralizing antibodies were uncommon,” Candela said.

Potential regulatory implications and expanded treatment landscape

Vedolizumab is currently approved for adults with moderate to severe ulcerative colitis, but pediatric approval has remained limited. The KEPLER trial was designed to support regulatory submissions to expand pediatric indications.

“The study results suggest that vedolizumab IV may help address gaps in the current treatment landscape for patients as young as 2 years old,” Candela said. “We aim to submit the marketing applications in the United States and the European Union this year for intravenous Entyvio for the treatment of moderate to severe ulcerative colitis.”

If approved, vedolizumab could represent an important addition to treatment options for pediatric UC, particularly for patients with refractory disease or prior biologic exposure.

References

1. Positive phase 3 data demonstrate potential for Entyvio (vedolizumab) to address treatment gap for children and adolescents with moderate to severe ulcerative colitis. News release. Takeda. February 19, 2026. Accessed February 19, 2026. https://www.takeda.com/newsroom/newsreleases/2026/entyvio-phase-3-pediatric-data/
2. Turner D, Kierkuś J, Korczowski B, et al. DOP037 Efficacy and safety of intravenous vedolizumab in paediatric patients with moderate to severe ulcerative colitis: results from the KEPLER phase 3 trial. J Crohns Colitis. 2026;20(suppl 1):jjaf231.074. doi:10.1093/ecco-jcc/jjaf231.074