Two Studies Shed Light on IBD Treatment After Anti-TNF Failure

Both tofacitinib (Xeljanz) and vedolizumab (Entyvio) are effective options for people with ulcerative colitis who fail at least one anti-tumor necrosis factor (anti-TNF) therapy, a real-world study in France revealed.

However, response was superior with tofacitinib among people after primary failure to biologics and multiple therapeutic failure, the researchers report, including endoscopic improvement and mucosal healing.  

Anthony Buisson, MD, presented the results February 18 at ECCO ’22 Virtual, the European Crohn’s and Colitis Organisation 2022 Congress.

The French Comparison

Although multiple therapeutic options are available to treat ulcerative colitis (UC) after anti-TNF failure, “there are no data comparing tofacitinib to vedolizumab in the real world,” said Buisson, a gastroenterologist at Clermont Auvergne University in Clermont-Ferrand, France.

In addition, network meta-analysis data are inconclusive, he said.

This led Buisson and colleagues to study adults with symptomatic UC with prior exposure to at least one anti-TNF treatment. They assessed 126 patients in a tofacitinib group and 178 in a vedolizumab group. The groups were comparable except for higher disease activity at baseline in the tofacitinib group.

The retrospective study was conducted at nine academic centers. Patients started either tofacitinib or vedolizumab between January 2019 and June 2021.

The primary endpoint, corticosteroid-free clinical remission at 16 weeks, was achieved by 45% of the tofacitinib group and 40% of the vedolizumab group. This difference was not statistically significant.

However, endoscopic improvement at week 16 did differ significantly, and was achieved by 24% of the tofacitinib group vs 7% of the vedolizumab group (P = .0036).

“Tofacitinib and vedolizumab are effective to induce corticosteroid-free clinical remission at week 16 in patients with UC who failed at least one anti-TNF agent,” Buisson said.

“Vedolizumab seems to be less effective in cases of more severe UC and prior history of primary failure to any biologic,” he added.

Buisson said he and his colleagues plan to continue the study beyond 16 weeks to look at long-term outcomes.

The Science From Spain

In another study presented at ECCO ’22 Virtual, investigators from Spain compared vedolizumab to ustekinumab (Stelara) after at least one anti-TNF treatment failure, this time among people with Crohn’s disease.

Finding effective treatments after an anti-TNF failure is essential, Maria Jose Garcia, MD, said when presenting the results of the VERSUS-CD trial. “Over 20% to 30% of Crohn’s disease patients are nonresponders or develop intolerance to anti-TNF therapies. Also, anti-TNF responders can experience a loss of response over time.”

Both vedolizumab and ustekinumab are effective for Crohn’s, she said. “But no clinical trial has compared both treatments, and limited data exist in real life.”

To remedy this situation, Garcia and colleagues studied 755 people from 30 medical centers in a national database in Spain who failed a previous anti-TNF agent, including 195 people switched to vedolizumab and 560 switched to ustekinumab. Luminal activity, perianal disease, or postoperative recurrence of Crohn’s were the indications for treatment.

The study’s main objective was to compare the short- and long-term treatment survival rate of vedolizumab and ustekinumab after anti-TNF therapy failure in clinical practice. Evaluating efficacy and safety were secondary aims.

“The treatment survival rate with ustekinumab was higher than with vedolizumab” over 5 years of follow-up, said Garcia, a gastroenterologist at Hospital Universitario Marqués de Valdecilla-IDIVAL in Santander, Spain. The difference was statistically significant (P < .001).

Just less than half (43%) of the 327 patients discontinued treatment over time, including 142 in the vedolizumab group and 185 in the ustekinumab group. The most frequent cause was primarily non-response.

Infection, arthralgia, and infusion reactions were the most common adverse events. The safety profile was similar between groups, Garcia said.

“In clinical practice, vedolizumab and ustekinumab are both effective after anti-TNF failure or intolerance in CD,” Garcia said. Adding that, “the retention rate of ustekinumab was higher compared to vedolizumab.”

When asked if the results will change how she practices, Garcia responded, “This confirms the first choice is ustekinumab more than vedolizumab in clinical practice, because it seems the clinical remission and durability of the treatment is superior.”

More Options Means More Questions

“Looking back almost 25 years ago, the struggle was how to work with just one biologic and how to make it last for patients who have already failed all the available therapies. All these years later, we have such riches that the question we most often deal with is ‘What’s my first treatment?’ for patients with inflammatory bowel disease,” Arun Swaminath, MD, told Medscape Medical News, when asked to comment on both studies.

“Increasingly, we are seeing industry do head-to-head trials of drugs, but this is a time-consuming and expensive process,” added Swaminath, chief of gastroenterology and director of the inflammatory bowel diseases program at Lenox Hill Hospital in New York City.

The study from Buisson and colleagues in UC approaches the design of a head-to-head trial, Swaminath said. “In the end, their primary endpoint was a statistical dead heat between the two options.”

In the VERSUS-CD study, vedolizumab was compared with ustekinumab “with more patients not discontinuing ustekinumab therapy compared to vedolizumab,” he said. “This study also seems to favor sicker patients being treated with ustekinumab.”

“In both cases, we are starting to see the ‘order’ of treatments take shape, even before the benefit of head-to-head trials,” Swaminath said.

Buisson reports receiving grant support from AbbVie, Celltrion, Pfizer, and Takeda, as well as personal fees from AbbVie, Amgen, Arena, Biogen, Celltrion, Ferring, Janssen, MSD, Nexbiome, Pfizer, Roche, sanofi-aventis, Takeda, Tillots, and Vifor Pharma. Garcia reports receiving financial support for traveling and educational activities from MSD, Janssen, AbbVie, Takeda, and Ferring. Swaminath reports receiving advanced IBD fellowship support from Janssen and Takeda and is on the advisory board for Boehringer Ingelheim.

ECCO 2022 Congress: DOP Abstract 76 and DOP Abstract 78. Presented February 18, 2022.

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on Twitter:  @MedReporter.

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