麻豆传媒

Vedolizumab (Entyvio) was more effective at inducing remission in patients with chronic pouchitis after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis compared with placebo, a randomized phase IV trial showed.

Among 102 patients, there was a difference of 21 percentage points (95% CI 5-38) in the incidence of modified Pouchitis Disease Activity Index (mPDAI)-defined remission at 14 weeks in favor of vedolizumab versus placebo (31% vs 10%, P=0.01), reported Simon Travis, DPhil, of the University of Oxford in England, and colleagues.

This effect "appeared to be sustained" to week 34 (35% vs 18%), with a difference of 17 percentage points (95% CI 0-35), and an analysis of PDAI-defined remission showed similar results at both time points, the group detailed in the .

Other secondary findings showed a difference of 30 percentage points (95% CI 8-48) favoring vedolizumab at week 14 for mPDAI-defined response (63% vs 33%), which dipped to 22 percentage points (95% CI 2-40) at week 34 (51% vs 29%).

"The results confirm what we have hypothesized -- that treatment of chronic pouchitis with vedolizumab can help improve both patients' symptoms and inflammation in patients with IPAA," Shannon Chang, MD, of the New York University Grossman School of Medicine, told 麻豆传媒.

Vedolizumab, a gut-selective monoclonal antibody, was approved by the FDA as a treatment for moderate-to-severe ulcerative colitis and Crohn's disease. The drug appeared to be effective in treating chronic pouchitis -- an idiopathic inflammation of the pouch that was created during restorative proctocolectomy, with symptoms that last longer than 4 weeks -- by reducing intestinal inflammation.

"Controlling mucosal inflammation ultimately prevents bowel damage," Travis and team concluded.

Pouchitis is a common complication of IPAA, which is routinely performed in patients with ulcerative colitis who undergo colectomy. It develops in about half of all patients within 5 years of the creation of the pouch and is recurrent in half of those patients, the researchers said. Chronic pouchitis occurs in about one in five patients.

Symptoms of pouchitis include increased stool frequency, abdominal gas, fecal urgency, and a poorer quality of life. The diagnosis is made primarily based on the presence of these symptoms and with a confirmation of inflammation based on an endoscopic exam or histology.

The current standard-of-care treatments for pouchitis vary based on whether it is acute or chronic, refractory to antibiotics, or involves Crohn's disease of the pouch, said Chang, who was not involved in the study. "Acute pouchitis is typically treated with antibiotics as needed, such as Cipro [ciprofloxacin] or Flagyl [metronidazole]. Chronic pouchitis can be treated with oral or topical steroids, mesalamines, or immune-suppressing medications, such as biologics or small molecules."

"It is worth noting that concomitant antibiotic use after week 4 was reported in a higher percentage of patients in the vedolizumab group than in the placebo group," she added. "Patients who start vedolizumab may sometimes also need courses of antibiotics to control pouchitis."

For this double-blind study, 102 patients were assigned in a 1:1 ratio to receive vedolizumab intravenously at a dose of 300 mg or placebo on day 1 and at 2, 6, 14, 22, and 30 weeks. All patients received concomitant ciprofloxacin from weeks 1 to 4. Antibiotics were also prescribed if needed for flares after week 14.

In the vedolizumab group, median patient age was 42, 63% were men, and 86% were white. In the placebo group, median age was 45, 74% were men, and 82% were white.

Adverse events among both groups included arthralgia, headache, nasopharyngitis, and nausea, among others. Serious adverse events occurred in 6% of the vedolizumab group and 8% of the placebo group.

Travis and team noted that although the PDAI and mPDAI are established measures for evaluating pouchitis, they have not been fully validated.

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