When anti–tumor necrosis factor-alpha (anti-TNF) treatment fails to achieve remission for patients with ulcerative colitis (UC), tofacitinib (Xeljanz) appears more effective sooner than vedolizumab (Entyvio), suggests a Dutch registry study.

Data on nearly 150 patients with UC who had already undergone treatment with anti-TNF drugs showed that combined clinical and biochemical remission was about five times more likely with tofacitinib vs vedolizumab within 12 weeks of starting therapy.

However, the differences tailed off over subsequent weeks, such that there was no significant difference in combined remission rates at 52 weeks. There were also no notable differences in safety between the two drugs.

“These results may help in guiding clinical decision-making after anti-TNF failure in patients with UC,” the authors write.

The research was published online by Clinical Gastroenterology and Hepatology.

Real-World Evidence

“This study offers more real-world evidence than a standard randomized controlled trial, since there was no randomization between the two study groups and no strict inclusion and exclusion criteria,” co–senior authors Tessa Straatmijer, MD, PhD candidate, and Marjolijn Duijvestein, MD, Amsterdam University Medical Center, the Netherlands, told Medscape Medical News.

They continued: “It is known that tofacitinib is more rapid of action compared to vedolizumab. We therefore expected that the odds ratio of remission rates between the two groups would be higher at weeks 12 and 24, compared to week 52.

“We will continue with collecting data in our prospective cohort up to 10 years after initiating tofacitinib or vedolizumab,” Straatmijer and Duijvestein added. “Hopefully we can provide long-term outcomes after a couple of years.”

The authors highlight that for a “considerable proportion” of patients with UC, their condition does not respond to anti-TNF drugs, they experience adverse effects, or the response diminishes over time. Alternatives, such as vedolizumab and tofacitinib, are typically “prescribed after failure of the anti-TNF,” owing to their price and clinician experience.

While vedolizumab (an α4β7 integrin blocker) and tofacitinib (a Janus kinase inhibitor) have different mechanisms of action, head-to-head randomized controlled trials comparing their efficacy among patients with UC whose condition is refractory to anti-TNF are “lacking,” they add. “However, to guide physician decision-making on the most suitable drug choice after anti-TNF failure, effectiveness data comparing tofacitinib with vedolizumab is pivotal.”

To assess the comparative effectiveness and safety of the next therapeutic options, the team examined data from the Dutch Initiative on Crohn and Colitis registry.

They identified nearly 300 adult patients with clinical or biochemical disease activity who had initiated treatment with vedolizumab or tofacitinib. They excluded patients without prior anti-TNF treatment, those who had previously been treated with vedolizumab or tofacitinib, and those who did not have clinical and biochemical or endoscopic disease activity at baseline. The final analysis included 83 patients given vedolizumab and 65 treated with tofacitinib.

Patients given tofacitinib received 10 mg twice daily for the first 8 weeks, followed by maintenance treatment of 5 mg twice daily, with optional dose optimization in case of insufficient response. Vedolizumab was administered intravenously in line with the label; 300 mg was administered at weeks 0, 2, and 6, followed by 300 mg every 8 weeks, with a shortened infusion interval in cases of inadequate response.

There were few differences between the two groups at baseline, although patients given vedolizumab had been treated longer than those in the tofacitinib group (12 years vs 7 years). Vedolizumab patients were also more likely to be receiving concomitant oral prednisone at baseline (50.6% vs 30.8%).

Early Difference Fades

Corticosteroid-free clinical remission at week 12 was observed in 27.7% of patients in the vedolizumab group, rising to 38.6% at week 24 and 37.3% at week 52. Among those given tofacitinib, the rates of clinical remission were 56.9% at week 12, 60.0% at week 24, and 55.4% at week 52.

Propensity score-weight analysis revealed that tofacitinib patients were more likely to achieve corticosteroid-free clinical remission at weeks 12, 24, and 52 in comparison with those given vedolizumab, at odds ratio of 6.33, 3.02, and 1.86, respectively.

Biochemical remission rates among patients treated with vedolizumab were 25.3% at week 12, 28.9% at week 24, and 22.9% at week 52. For the tofacitinib group, the rates were 40.0%, 36.9%, and 27.7%, respectively. Biochemical remission was defined by C-reactive protein or fecal calprotectin levels.

The likelihood of biochemical remission was again greater with tofacitinib than with vedolizumab, at an odds ratio of 3.27 at week 12, 1.87 at week 24, and 1.81 at week 52.

Combined clinical and biochemical remission was more likely among patients given tofacitinib vs vedolizumab at week 12, at an odds ratio of 5.05, and at week 24, at an odds ratio of 2.11. However, at week 52, the difference was no longer significant, at an odds ratio of 1.17.

The authors note that there was no difference in the rate of infection between the two treatment groups, and the rate of severe adverse events was similar. However, three patients receiving tofacitinib experienced herpes simplex infections, compared with none of those given vedolizumab.

But compared to the tofacitinib group, patients taking vedolizumab were more likely to discontinue treatment before 52 weeks, primarily because of a lack of response to treatment.

“The present study underlines that both vedolizumab and tofacitinib are relatively safe treatment options in patients with UC in a 12-month period,” the team writes.

“Interesting” Efficacy Data

Approached for comment, Alan C. Moss, MD, a professor of gastroenterology at Boston University School of Medicine in Massachusetts, said that the findings are “interesting” for clinicians.

“We have so many treatment options right now, picking one over the other, particularly in patients like this who fail anti-TNF, is very important,” he told Medscape Medical News.

While he noted that registry data such as these are usually powered for “one outcome” (either efficacy or safety), “the immediate conclusions that come to mind are that certainly the efficacy of the two drugs in this patient population looks impressive.

“What we do note, though, is over time, as you get longer into the study, they start to become closer in terms of overall remission,” which Moss said fits with the current understanding that vedolizumab “takes longer to work.”

The take-away lesson from the study is that the short-term efficacy of tofacitinib is “superior,” Moss said, but, over the medium to long term, vedolizumab “may turn out to be more equivalent.”

Moss also pointed out that approximately 40% of patients given tofacitinib in the study began with the higher 10-mg twice-daily dose, “which is not the FDA-approved maintenance dose, and over time about a quarter stayed on the higher dose.

“What that tells us is that, yes, it works faster if you’re using the higher dose, and over time, a certain proportion of these patients needed a higher dose to get these results,” he said.

Consequently, Moss said that the two treatment groups were not “equivalent” in terms of the doses given relative to normal maintenance dose.

The Initiative on Crohn and Colitis Fellowship is sponsored by AbbVie, Pfizer, Takeda, Celgene, Janssen Pharmaceutica, Teva Pharmaceutical Industries, Cablon Medical, Ferring Pharmaceuticals, Mundipharma, Dr Falk Pharma, Sandoz, and Tramedico. Duijvestein has relationships with Echo Pharma, Robarts Clinical Trials, Inc, Janssen, Merck & Co, Inc, Pfizer, Takeda, Tillotts Pharma, and Dr Falk Pharma. Other authors have numerous relationships with industry. Moss has relationships with Pfizer and Janssen.

Clin Gastroenterol Hepatol. Published online May 25, 2022. Full text

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