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Vedolizumab (Entyvio) was superior to adalimumab (Humira) for clinical remission and endoscopic mucosal healing in moderate-to-severe active ulcerative colitis at 52 weeks, according to a presentation at the European Crohn's and Colitis Organisation congress in Copenhagen.

Findings from the showed that 31.3% (n=120/383) of patients who received IV vedolizumab achieved the trial's primary endpoint of clinical remission -- defined as a total Mayo score ≤2 with no subscore >1 -- at week 52, compared with 22.5% (n=87/386) of those treated with subcutaneous (SC) adalimumab at week 52, for a statistically significant difference (P=0.0061), according to Bruce E. Sands, MD, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues.

Furthermore, at week 52, vedolizumab was associated with significantly higher rates of mucosal healing (Mayo endoscopic sub-score ≤1), with 39.7% of the vedolizumab arm achieving this outcome versus 27.7% in the adalimumab arm (P=0.0005). A non-statistically significant difference in favor of adalimumab was seen in the percentage of patients using oral corticosteroids at baseline, who then discontinued corticosteroids and were in clinical remission at week 52.

VARSITY, sponsored by vedolizumab manufacturer Takeda, was the first prospective of two biologics for moderate-to-severe active UC. Vedolizumab is a gut-selective inhibitor of the adhesion molecule integrin alpha-4 beta-7, while adalimumab is a tumor necrosis factor (TNF) alpha inhibitor.

"The VARSITY study addresses critical questions concerning the selection of biologic therapy in ulcerative colitis," Sands said in a . "The goal of treatment in ulcerative colitis is to achieve clinical remission and mucosal healing, and these results clearly highlight the benefits seen with vedolizumab versus adalimumab on these important outcomes."

Sands added that fewer overall and serious adverse events, including infections, occurred in patients treated on vedolizumab versus adalimumab.

VARSITY recruited patients at 333 sites in 37 countries. The phase IIIb, double-blind, double-dummy, active-controlled trial randomized 769 refractory patients to standard doses of vedolizumab at active IV infusions of 300 mg/placebo SC injections (n=383) or adalimumab at active SC injections (160/80/40 mg)/placebo IV infusions (n=386). No dose escalation was allowed. Prior TNF inhibitor exposure was capped at 25% of the patient population, the authors stated.

While the study was not powered to compare the safety of the two biologics, both agents were generally safe and well tolerated. Patients treated with vedolizumab had a lower rate of overall adverse events over 52 weeks than those receiving adalimumab at 62.7% versus 69.2%. There was a lower rate of infections with vedolizumab (33.5%) compared with adalimumab (43.5%). The rate of serious adverse events was also slightly lower in vedolizumab-treated patients (11.0% vs 13.7%).

"As this is the first prospective, head-to-head study of two biologics in UC, these findings will likely impact the clinical positioning of these two agents," noted Benjamin H. Click, MD, of the Cleveland Clinic in Ohio to 番茄社区.

"At standard doses, the results seem to favor vedolizumab over adalimumab," said Click, who was not involved in the study. "However, important study limitations may dampen the full clinical impact."

Click cited the inclusion of anti-TNF-experienced participants, and the lack of dose escalation as limitations, and suggested that factors other than the mechanism of action may have partially accounted for the observed outcome differences.

"Regardless, this study should be lauded as ushering in a new era of prospective comparative effectiveness studies in IBD [inflammatory bowel disease]," he said.

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