S785 Alicaforsen Enema in Chronic Pouchitis: Results of a Phase 3 Randomized, Double-blind, Placebo-controlled Trial
Bibliographic record
Abstract
Introduction: Antibiotic refractory pouchitis is an intractable disorder with no evidence based medical therapies available. Alicaforsen, a selective, antisense oligonucleotide that inhibits ICAM-1 was evaluated in the largest ever randomized, placebo-controlled trial. Methods: 138 subjects were randomised in a 1:1 ratio to 240 mg alicaforsen or placebo enema, self-administered once daily. Eligible subjects had active pouchitis for at least 4 weeks defined as a Mayo endoscopy score modified for pouchitis of ≥2, stool frequency of ≥6 stools and ≥3 stools per day above the post IPAA baseline, and histology. Following a 6-week treatment course subjects were followed for safety assessment for the sooner of 20 weeks or disease flare. The primary objectives were to determine the effect of alicaforsen enema on endoscopic remission and stool frequency at week 10. Secondary objectives included assessment of safety and tolerability, changes in histology and pharmacokinetic analysis. Results: At Week 10, 94% of subjects in the alicaforsen and placebo groups had a unchanged modified Mayo Endoscopy Score making the odds ratio of endoscopic remission 0.93 (95% CI: 0.181, 4.819). It was found that ulceration covered a minimal area of the pouch, hence questioning the value of modified Mayo endoscopy score for patient selection or efficacy. Whilst 33.8% of subjects in the alicaforsen vs 26.2% in the placebo group achieved clinical remission, with an odds ratio of 1.44 (95% CI: 0.668, 3.103). There were no differences for any of the secondary endpoints. Although the treatment was safe and well tolerated, 33.3% of subjects in the alicaforsen and 36.2% in the placebo group dropped out. Pharmacokinetic data confirmed minimal systemic exposure to alicaforsen. Conclusion: The study demonstrates the clinical benefit of alicaforsen enema in chronic pouchitis as determined by improvement of stool frequency and confirms its safety and tolerability. The modified Mayo endoscopy score is inappropriate for patient selection and disease assessment in chronic pouchitis. Statistical efficacy analysis was likely to have been compromised by the 35% discontinuation rate, a result of disallowing antibiotics and rectal budesonide. In view of the possible clinical benefits, robust safety and tolerability of alicaforsen enema; further evaluation is warranted not only in chronic pouchitis but also with priority in distal ulcerative colitis which has better defined measures for patient selection and treatment assessment.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".