Vedolizumab Beats Infliximab as Second-Line UC Therapy

BERLIN — Ulcerative colitis (UC) patients who fail on first-line therapy appear to have better outcomes with vedolizumab (Entyvio) than with infliximab, suggests EFFICACI, the first trial directly comparing second-line advanced therapies in patients with the disease.

Vedolizumab was superior to infliximab to achieving steroid-free clinical remission at week 14 in patients who had failed on a first-line subcutaneous anti–tumor necrosis factor (anti-TNF) therapy, said study presenter Guillaume Bouguen, MD, PhD, of the Gastroenterology Department, CHU Rennes – Pontchaillou Hospital, Rennes, France.

The drug also outperformed infliximab in the induction of endoscopic improvement, and its safety outcomes were “consistent with the known profile of both drugs in previous trials,” Bouguen said.

The research was presented at the European Crohn’s and Colitis Organisation 2src25 Congress.

The study reports only short-term outcomes, so it “remains unclear whether vedolizumab’s advantage is sustained over time or whether infliximab may catch up in effectiveness,” Tauseef Ali, MD, executive medical director, SSM Health St. Anthony Digestive Care, Crohn’s and Colitis Center, Oklahoma City, Oklahoma, told Medscape Medical News.

Bouguen noted that the trial was unblinded at week 14 and that patients were followed-up to week 54, data for which will be presented in the near future.

Head-to-Head Trial

Treating ulcerative colitis beyond the first line of therapy is “becoming challenging” because there are several therapeutic classes and drugs to choose from but no strong evidence to support physician decision-making, Bouguen said.

No head-to-head trials for second-line advanced therapies for UC had been performed, he said. So Bouguen and colleagues conducted a randomized, double-blind trial to determine whether vedolizumab, an integrin receptor agonist, is superior to infliximab, a TNF antagonist, in ulcerative colitis patients who had failed a first-line subcutaneous TNF antagonist.

They enrolled patients with moderate to severe disease, defined by a total Mayo score ≥ 6, despite at least 12 weeks of treatment with the TNF antagonists golimumab (Simponi) or adalimumab (Humira and others), from 24 centers across France.

Participants were randomly assigned to intravenous 3srcsrc mg vedolizumab or 5 mg/kg infliximab. Clinical biological assessments performed at baseline and at weeks 2 and 6. The primary endpoint was steroid-free clinical remission (Mayo score ≤ 2) at week 14.

Of 165 patients assessed for eligibility, 78 were randomly assigned to vedolizumab and 73 to infliximab, of whom 77 and 7src and patients, respectively, were available for assessment at week 14. Approximately 4src% of the participants were women, and the average age was almost 4src years.

The mean total Mayo score at baseline was comparable between the two groups (9.src vedolizumab; 8.7 infliximab). The majority in both groups had previously been treated with adalimumab, and almost 6src% had had experienced a loss of response to therapy.

Steroid-free clinical remission at week 14 was achieved by 34.6% of patients treated with vedolizumab vs 19.2% of those given infliximab (P=.src33).

Endoscopic remission at week 14 was achieved by 19.5% of patients in the vedolizumab group vs 8.3% of those treated with infliximab (P=.src5src7), while endoscopic improvement was seen in 46.8% and 29.2% of patients, respectively (P=.src273).

There were no statistically significant differences between the two treatment groups in rates of clinical response or mean C-reactive protein (CRP) levels between baseline and week 14, and there was no significant difference in fecal calprotectin levels at week 14.

Interestingly, Bouguen said that, from parameters such as age, sex, Mayo score, CRP levels, and concomitant immunosuppressant use, there were no significant predictors of clinical remission.

The overall incidence of adverse events, including respiratory tract and Clostridioides difficile infections, was comparable between the vedolizumab and infliximab groups, although patients receiving infliximab had higher rates of disease worsening and infusion reactions.

Questions Remain

Study co-investigator Matthieu Allez, MD, PhD, head of the Gastroenterology Department, Hôpital Saint-Louis, Assistance Publique Hopitaux de Paris, Paris, France, told Medscape Medical News that he was surprised by the findings.

“I think infliximab is a much better drug than vedolizumab,” considering the rate of immunosuppressant combination therapy that is administered in ulcerative colitis, said Allez, who was the session’s co-chair.

This is a “key aspect” as “you can give more” of such therapy to patients receiving infliximab, “but, in fact, it seems like they do better” with vedolizumab, Allez said.

Ali told Medscape Medical News that the trial “addresses a critical gap in the treatment of ulcerative colitis: Whether switching within the anti-TNF class or swapping to vedolizumab is more effective after failure of a first subcutaneous anti-TNF.”

“This question has real-world clinical relevance, as gastroenterologists often face this decision,” he added.

Ali, who was not involved in the study, said that even though the results “suggest that vedolizumab may be a more effective option than infliximab in this patient population” and there were no major safety concerns with either drug, “one must exercise caution in interpreting and applying the results to clinical practice.”

Moreover, the lack of statistically significant clinical response rates between the drugs “raises questions about whether the primary endpoint difference is clinically meaningful over the long term,” he said.

The study was conducted in only one country, thus potentially limiting its generalizability, Ali noted, and it included only patients who had failed on subcutaneous, not intravenous, anti-TNF therapy. There was also a lack of biomarker stratification, “making it unclear which patients would benefit most from switching vs swapping strategies,” he added.

“While vedolizumab may be preferable, many other factors,” such as drug serum levels, immunogenicity, urgency of response, access, and cost, “should guide decision-making,” Ali said.

The study was funded by the French national research program, with additional funding from Takeda.

Bouguen declared relationships with Abb