Vedolizumab for the Treatment of Chronic Pouchitis.

Abstract

BACKGROUND:

Approximately half the patients with ulcerative colitis who undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) will subsequently have pouchitis, and among those patients, one fifth will have chronic pouchitis.

METHODS:

We conducted a phase 4, double-blind, randomized trial to evaluate vedolizumab in adult patients in whom chronic pouchitis had developed after undergoing IPAA for ulcerative colitis. 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 weeks 2, 6, 14, 22, and 30. All the patients received concomitant ciprofloxacin from weeks 1 to 4. The primary end point was modified Pouchitis Disease Activity Index (mPDAI)-defined remission (an mPDAI score of ≤4 and a reduction from baseline of ≥2 points in the mPDAI total score; scores range from 0 to 12, with higher scores indicating more severe pouchitis) at week 14. The mPDAI is based on clinical symptoms and endoscopic findings. Other efficacy end points included mPDAI-defined remission at week 34, mPDAI-defined response (a reduction from baseline of ≥2 points in the mPDAI score) at weeks 14 and 34, and PDAI-defined remission (a PDAI score of ≤6 and a reduction from baseline of ≥3 points; scores range from 0 to 18, with higher scores indicating more severe pouchitis) at weeks 14 and 34. The PDAI is based on clinical symptoms, endoscopic findings, and histologic findings.

RESULTS:

Among the 102 patients who underwent randomization, the incidence of mPDAI-defined remission at week 14 was 31% (16 of 51 patients) with vedolizumab and 10% (5 of 51 patients) with placebo (difference, 21 percentage points; 95% confidence interval [CI], 5 to 38; P = 0.01). Differences in favor of vedolizumab over placebo were also seen with respect to mPDAI-defined remission at week 34 (difference, 17 percentage points; 95% CI, 0 to 35), mPDAI-defined response at week 14 (difference, 30 percentage points; 95% CI, 8 to 48) and at week 34 (difference, 22 percentage points; 95% CI, 2 to 40), and PDAI-defined remission at week 14 (difference, 25 percentage points; 95% CI, 8 to 41) and at week 34 (difference, 19 percentage points; 95% CI, 2 to 37). Serious adverse events occurred in 3 of 51 patients (6%) in the vedolizumab group and in 4 of 51 patients (8%) in the placebo group.

CONCLUSIONS:

Treatment with vedolizumab was more effective than placebo in inducing remission in patients who had chronic pouchitis after undergoing IPAA for ulcerative colitis. (Funded by Takeda; EARNEST ClinicalTrials.gov number, NCT02790138; EudraCT number, 2015-003472-78.).

• Authors: Simon Travis, Mark S Silverberg, Silvio Danese, Paolo Gionchetti, Mark Löwenberg, Vipul Jairath, Brian G Feagan, Brian Bressler, Marc Ferrante, Ailsa Hart, Dirk Lindner, Armella Escher, Stephen Jones, Bo Shen, EARNEST Study Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 388 Issue 13 Pg. 1191-1200 (Mar 30 2023) ISSN: 1533-4406 [Electronic] United States
• PMID: 36988594 (Publication Type: Clinical Trial, Phase IV, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2023 Massachusetts Medical Society.

Chemical References

• Antibodies, Monoclonal, Humanized
• Ciprofloxacin
• vedolizumab
• Gastrointestinal Agents
• Anti-Bacterial Agents

Topics

• Adult
• Humans
• Antibodies, Monoclonal, Humanized (administration & dosage, therapeutic use)
• Ciprofloxacin (administration & dosage, therapeutic use)
• Colitis, Ulcerative (complications, surgery)
• Pouchitis (drug therapy, etiology)
• Chronic Disease
• Gastrointestinal Agents (administration & dosage, therapeutic use)
• Proctocolectomy, Restorative (adverse effects)
• Double-Blind Method
• Anti-Bacterial Agents (administration & dosage, therapeutic use)
• Administration, Intravenous
• Drug Therapy, Combination