Vedolizumab Outperforms Infliximab in Second-Line Therapy for Ulcerative Colitis

Patients with ulcerative colitis (UC) who do not respond to first-line therapy show better outcomes with vedolizumab (Entyvio) than with infliximab, according to a trial, which is the first to directly compare second-line treatments for the disease. Vedolizumab was more effective than infliximab in achieving steroid-free clinical remission by week 14 in patients who had failed a first-line subcutaneous anti-TNF therapy, as reported by Guillaume Bouguen, M.D., Ph.D., from CHU Rennes – Pontchaillou Hospital, France. The drug also outperformed infliximab in inducing endoscopic improvement, with safety outcomes aligning with prior trial profiles for both medications (1^✔ ✔Trusted Source
European Union Clinical Trials Register

Go to source). The research was presented at the European Crohn’s and Colitis Organisation 2025 Congress.

The study reports only short-term outcomes, so it remains unclear whether vedolizumab's advantage will last or if infliximab may become more effective over time, said Tauseef Ali, M..D, AGAF, executive medical director at SSM Health St. Anthony Digestive Care, Oklahoma City. Bouguen noted that the trial was unblinded at week 14, with follow-up data up to week 54 to be presented soon.

Challenges in Treating Ulcerative Colitis Beyond First-Line Therapy

Treating ulcerative colitis beyond the first line is becoming increasingly challenging due to numerous therapeutic options and a lack of strong evidence to guide decision-making, according to Bouguen. Prior to this, no head-to-head trials had compared second-line advanced therapies for UC. To fill this gap, Bouguen and colleagues conducted a randomized, double-blind trial to assess whether vedolizumab, an integrin receptor agonist, is superior to infliximab, a TNF antagonist, in patients who had failed a first-line subcutaneous TNF antagonist.

The trial enrolled patients with moderate to severe disease despite at least 12 weeks of treatment with golimumab (Simponi) or adalimumab (Humira), from 24 centers across France. Participants were randomly assigned to receive either 300 mg of intravenous vedolizumab or 5 mg/kg of infliximab. Clinical assessments were made at baseline and at weeks 2 and 6, with the primary endpoint being steroid-free clinical remission at week 14.

Of the 165 patients assessed for eligibility, 78 were assigned to vedolizumab and 73 to infliximab, with 77 and 70 patients, respectively, available for assessment at week 14. About 40% of participants were women, with an average age of nearly 40 years.

Most patients in both groups had previously been treated with adalimumab, and nearly 60% had experienced a loss of response to therapy.

Steroid-Free Clinical Remission: Vedolizumab vs Infliximab

At week 14, 34.6% of patients treated with vedolizumab achieved steroid-free clinical remission, compared to 19.2% in the infliximab group. Endoscopic remission was achieved by 19.5% of patients on vedolizumab vs 8.3% on infliximab, and endoscopic improvement was observed in 46.8% vs 29.2%, respectively.

There were no significant differences between the two groups in clinical response rates or mean C-reactive protein (CRP) levels from baseline to week 14, and no significant difference in fecal calprotectin levels at week 14. Bouguen noted that factors like age, sex, Mayo score, CRP levels, and concomitant immunosuppressant use were not significant predictors of clinical remission.

The overall incidence of adverse events, including respiratory tract and Clostridioides difficile infections, was similar between the two groups, although patients on infliximab experienced higher rates of disease worsening and infusion reactions.

Questions remain about the findings, as study coinvestigator Matthieu Allez, M.D., Ph.D., expressed surprise, noting that infliximab is generally considered a stronger treatment for ulcerative colitis, especially when used with combination immunosuppressant therapy. He emphasized that while more therapy can be given with infliximab, vedolizumab appears to show better results.

Addressing a Critical Gap in Ulcerative Colitis Treatment

Tauseef Ali, M.D., AGAF, highlighted the trial’s importance in addressing a critical gap in UC treatment: whether switching within the anti-TNF class or switching to vedolizumab is more effective after a first-line anti-TNF fails. However, while the trial suggests vedolizumab may be more effective than infliximab, Ali cautioned that the results should be interpreted carefully for clinical practice, particularly given the lack of significant differences in clinical response rates between the two drugs.

Ali also pointed out the study's limitations, such as being conducted in just one country, involving only patients who failed subcutaneous anti-TNF therapy, and lacking biomarker stratification. He emphasized that factors like drug serum levels, immunogenicity, urgency of response, access, and cost should also guide decision-making.

Reference:

1. European Union Clinical Trials Register - (https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-002673-21/FR)

Source-GI & Hepatology News