PREVENTCD · Surgery
Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease After Ileocolonic Resection
Regueiro M, et al.
Gastroenterology 2016 · PMID 26946343 (PubMed, opens in a new tab) · doi 10.1053/j.gastro.2016.02.072 (full paper, opens in a new tab)
| Outcome | Infliximab | Placebo | Estimate (confidence interval) | P |
|---|---|---|---|---|
| Clinical recurrence, Primary endpoint · by week 76 (primary) | 12.9% | 20.0% | +7.1 (95% CI −1.3 to 15.5) | P=0.097 |
| Endoscopic recurrence, Major secondary endpoint | 30.6% | 60.0% | +29.4 (95% CI 18.6–40.2) | P<0.001 |
| Endoscopic recurrence, Rutgeerts ≥i2 alone | 22.4% | 51.3% | +28.9 (95% CI 18.4–39.4) | P<0.001 |
Infliximab roughly halved endoscopic recurrence but did not significantly reduce the clinical composite by week 76.
Source: Regueiro 2016, abstract. Differences are absolute risk reductions as printed.
Structured abstract
BackgroundCrohn's disease often recurs after ileocolonic resection. Small trials suggested that infliximab prevents endoscopic recurrence, but its effect on clinical recurrence needed a large placebo-controlled trial.
MethodsRandomised, double-blind, placebo-controlled trial (104 sites). 297 patients. Primary endpoint: Clinical recurrence before or at week 76: CDAI above 200 with a rise of ≥70 points plus endoscopic recurrence (Rutgeerts ≥i2, central reader), or a new or re-draining fistula or abscess.
ResultsPrimary result. 12.9% vs 20.0%; absolute risk reduction 7.1% (95% CI −1.3% to 15.5%); P=0.097 (not significant).
Take-homeIn patients at increased risk, postoperative infliximab roughly halves endoscopic recurrence but did not significantly reduce clinical recurrence by week 76, so endoscopic monitoring is still needed.
| Patients | 297 |
|---|---|
| Population | Patients with Crohn's disease at increased risk of recurrence (per the trial registration) who had an ileocolonic resection within 45 days before randomisation; macroscopic disease left unresected was excluded. |
| Comparison | Infliximab 5 mg/kg vs placebo every 8 weeks (planned for 200 weeks) |
| Drugs | infliximab |
| Classes | Anti-TNF |
| Published | Regueiro M, et al. Gastroenterology 2016;150:1568–78. |
Key points
- Endoscopic recurrence (major secondary endpoint): 30.6% vs 60.0%; absolute risk reduction 29.4% (95% CI 18.6%–40.2%); P<0.001.
- Endoscopic recurrence by Rutgeerts ≥i2 alone: 22.4% vs 51.3%; absolute risk reduction 28.9% (95% CI 18.4%–39.4%); P<0.001.
- Previous anti-TNF exposure and more than one resection increased the risk of clinical recurrence.
- Safety was similar to previous infliximab reports.
Limitations
- The primary clinical endpoint required both symptoms and endoscopic recurrence (or a fistula or abscess); endoscopic recurrence was a secondary endpoint.
- 76-week primary analysis; clinical recurrence lags behind endoscopic recurrence.
- Industry sponsored (Janssen Biotech, per the trial registration).
Commentary
PREVENT is the largest placebo-controlled trial of postoperative biologic prophylaxis. The gap between endoscopic and clinical results reflects the time lag between endoscopic recurrence and symptoms. Together with POCER, it supports anti-TNF prophylaxis for high-risk patients and colonoscopy-guided escalation for the rest.
Journal club
Design
Randomised, double-blind, placebo-controlled trial (104 sites). 297 patients.
Primary result. 12.9% vs 20.0%; absolute risk reduction 7.1% (95% CI −1.3% to 15.5%); P=0.097 (not significant).
Validity and applicability
- The primary clinical endpoint required both symptoms and endoscopic recurrence (or a fistula or abscess); endoscopic recurrence was a secondary endpoint.
- 76-week primary analysis; clinical recurrence lags behind endoscopic recurrence.
- Industry sponsored (Janssen Biotech, per the trial registration).
Where it sits now
In patients at increased risk, postoperative infliximab roughly halves endoscopic recurrence but did not significantly reduce clinical recurrence by week 76, so endoscopic monitoring is still needed.
- POCER (2015): After resection, treating by risk and scoping at 6 months with step-up for recurrence beats drug prophylaxis alone; this is why we do a postoperative colonoscopy.
- REPREVIO (2025): Starting vedolizumab within 4 weeks of ileocolonic resection reduces early endoscopic recurrence in patients at risk.
- SPICY (2024): Removing more mesentery at primary ileocolic resection did not reduce 6-month endoscopic recurrence, and leaks were numerically more common.
- LIR!C (2017): For limited (40 cm or less), non-stricturing terminal ileal Crohn's disease that has failed conventional therapy, laparoscopic resection is a reasonable alternative to starting an anti-TNF.
Questions for discussion
- The primary endpoint required both symptoms and endoscopic recurrence. Was that the right primary endpoint for a 76-week trial?
- Should every patient get prophylaxis after ileocolonic resection, or only those at high risk, with colonoscopy-guided step-up as in POCER?
- Patients previously treated with an anti-TNF had a higher risk of clinical recurrence. Would you choose a different drug for them after surgery?