OP04 Vedolizumab intravenous is effective across multiple treatment targets in chronic pouchitis: Results of the randomised, double-blind, placebo-controlled EARNEST trial
Bibliographic record
Abstract
Abstract Background Pouchitis is a common complication of ileal pouch-anal anastomosis (IPAA) after proctocolectomy in ulcerative colitis (UC). There are currently no approved therapies for chronic pouchitis. Here, we report a multicentre trial of intravenous (IV) vedolizumab (VDZ) for chronic pouchitis after IPAA in patients with UC. Methods EARNEST was a randomised, double-blind, placebo (PBO)-controlled, phase 4 study of VDZ in patients aged 18–80 years with chronic pouchitis after proctocolectomy with IPAA for UC (NCT02790138). Male and female patients with a history of IPAA for UC and chronic pouchitis were eligible. Patients were randomised (1:1) to receive VDZ IV (300 mg) or PBO on Day 1 and at Weeks (W) 2, 6, 14, 22 and 30, as well as ciprofloxacin for the first 4 weeks. The primary endpoint was modified Pouchitis Disease Activity Index (mPDAI) remission at W14; efficacy was also assessed through other mPDAI/PDAI secondary endpoints and endoscopic exploratory endpoints (assessed by a central reviewer) at W14 and W34. Safety (adverse events [AEs]) was monitored throughout the study. Results In total, 102 patients were treated (51 per group). Patients had a mean age of 40.8 years (VDZ) and 42.9 years (PBO). mPDAI remission rates (comprising clinical symptoms and endoscopy domains) were 31.4% (n=16/51) for VDZ vs 9.8% (n=5/51) for PBO at W14 (p=0.013; Figure 1). Significant differences in favour of VDZ over PBO were also seen in mPDAI remission at W34, mPDAI response at W14 and W34, and PDAI remission (comprising clinical symptoms, endoscopy and histology domains) at W14 and W34 (Figure 1). The rate of sustained remission (defined as remission at both W14 and W34) was higher for VDZ vs PBO on both the mPDAI (VDZ 27.5% [n=14/51] vs PBO 5.9% [n=3/51]; difference 21.6 percentage points [95% confidence interval (CI), 6.5–37.0]) and the PDAI (VDZ 31.4% [n=16/51] vs PBO 7.8% [4/51]; difference 23.5 percentage points [95% CI, 8.0–38.8]). Endoscopic ulceration analysis showed greater reductions in number of ulcers from baseline for VDZ over PBO at W14 and W34 (Figure 2). A higher proportion of patients in the VDZ vs PBO group had an improved SES-CD score and achieved SES-CD remission of pouchitis (Figure 2). AE rates were similar between groups and no new safety signals were identified (Table). Conclusion This is the first and largest randomised, double-blind PBO-controlled trial of biologic therapy to show significant benefits across multiple treatment outcomes in patients with chronic pouchitis after IPAA for UC. VDZ showed consistent treatment benefits over PBO across clinical, endoscopic and histologic endpoints, together with safety consistent with its established profile.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".