EARNESTPouchitis · Induction and maintenance
Vedolizumab for the Treatment of Chronic Pouchitis
Travis S, et al.
N Engl J Med 2023 · PMID 36988594 (PubMed, opens in a new tab) · doi 10.1056/NEJMoa2208450 (full paper, opens in a new tab)
| Outcome | Vedolizumab | Placebo | Estimate (confidence interval) | P |
|---|---|---|---|---|
| mPDAI remission, Week 14 · primary endpoint (primary) | 31% (16/51) | 10% (5/51) | +21 (95% CI 5–38) | P=0.01 |
| mPDAI remission, Week 34 | +17 (95% CI 0–35) | |||
| mPDAI response, Week 14 | +30 (95% CI 8–48) | |||
| mPDAI response, Week 34 | +22 (95% CI 2–40) | |||
| PDAI remission, Week 14 | +25 (95% CI 8–41) | |||
| PDAI remission, Week 34 | +19 (95% CI 2–37) |
Every endpoint favoured vedolizumab, although the lower bound for week-34 remission reaches zero.
Source: Travis 2023, abstract. mPDAI remission: score ≤4 and down ≥2 points; mPDAI response: down ≥2 points; PDAI remission: score ≤6 and down ≥3 points. Per-arm rates are given only for the primary endpoint.
Structured abstract
BackgroundChronic pouchitis after IPAA for UC is common and often antibiotic-dependent or refractory, and no advanced therapy had been tested against placebo in a randomised trial.
MethodsPhase 4, double-blind, randomised, placebo-controlled trial. 102 patients. Primary endpoint: Modified Pouchitis Disease Activity Index (mPDAI) remission at week 14: mPDAI ≤4 with a reduction of ≥2 points from baseline.
ResultsPrimary result. 31% (16/51) with vedolizumab vs 10% (5/51) with placebo; difference 21 percentage points (95% CI 5–38); P=0.01.
Take-homeVedolizumab is the first advanced therapy shown in a randomised trial to induce remission in chronic pouchitis.
| Patients | 102 |
|---|---|
| Population | Adults with chronic pouchitis after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis. |
| Comparison | Vedolizumab 300 mg IV vs placebo on day 1 and weeks 2, 6, 14, 22 and 30; all patients received ciprofloxacin from weeks 1 to 4 |
| Drugs | vedolizumab, ciprofloxacin |
| Classes | Anti-integrin |
| Published | Travis S, et al. N Engl J Med 2023;388:1191–1200. |
Key points
- mPDAI remission at week 34: difference 17 percentage points (95% CI 0–35).
- mPDAI response (reduction ≥2 points): difference 30 percentage points (95% CI 8–48) at week 14 and 22 (2–40) at week 34.
- PDAI remission: difference 25 percentage points (95% CI 8–41) at week 14 and 19 (2–37) at week 34.
- Serious adverse events: 6% (3/51) vedolizumab vs 8% (4/51) placebo.
Limitations
- Modest absolute remission rate (31%).
- Antibiotic co-treatment in both arms in the first 4 weeks.
- Patients with Crohn's disease of the pouch were not the target population.
- Industry funded (Takeda).
Commentary
About half of patients with an IPAA for ulcerative colitis develop pouchitis, and about one in five of those develop chronic pouchitis. Before EARNEST, the use of biologics for chronic antibiotic-dependent or refractory pouchitis relied on observational data. EARNEST is the main randomised evidence for an advanced therapy in this setting. Evaluate for Crohn’s-like disease of the pouch, cuffitis and other causes before labelling pouchitis as chronic.
Journal club
Design
Phase 4, double-blind, randomised, placebo-controlled trial. 102 patients.
Primary result. 31% (16/51) with vedolizumab vs 10% (5/51) with placebo; difference 21 percentage points (95% CI 5–38); P=0.01.
Validity and applicability
- Modest absolute remission rate (31%).
- Antibiotic co-treatment in both arms in the first 4 weeks.
- Patients with Crohn's disease of the pouch were not the target population.
- Industry funded (Takeda).
Where it sits now
Vedolizumab is the first advanced therapy shown in a randomised trial to induce remission in chronic pouchitis.
Questions for discussion
- The mPDAI drops histology from the PDAI. What are the advantages and drawbacks of each for trials and for practice?
- All patients took ciprofloxacin for the first 4 weeks. How might that affect the week-14 result?
- Before calling pouchitis chronic and starting a biologic, which other diagnoses would you exclude?