In 2009, Regueiro and colleagues published an influential paper “Infliximab prevents Crohn’s disease recurrence after ill resection” (Gastroenterol 2009; 136: 441-50). However, this was a small study with only 24 patients. In this study, only 1 of 11 patients on infliximab had endoscopic recurrence compared with 11 of 13 of placebo patients at 1 year. Besides the promising result that infliximab may prevent recurrent Crohn’s disease, this study confirmed that there is poor correlation between endoscopic recurrence and clinical activity scores. In addition, the implication was that early treatment could be very important.
Now, a much larger study has been published (M Regueiro et al. Gastroenterol 2016; 150: 1568-78) and has cast some doubt on these earlier findings. It may have “muddied the waters” regarding the optimal approach. The authors conclude that infliximab reduces postoperative endoscopic, but not clinical, recurrence of Crohn’s disease. Furthermore, they recommend in their discussion: “it may be reasonable to approach low-risk patients undergoing their first resection for CD conservatively and initiate treatment only if there is endoscopic recurrence at 6 months” [post-op]. The associated editorial (1521-24), after highlighting some of the important clinical findings, also says, that it may be “difficult to convince payers and patients that >2-4 years of treating an asymptomatic patient with TNFi, with its potential risks of long-term adverse effects, will be required to prevent clinically meaningful endpoints.”
Before accepting these conclusions, a closer look at the study is important. This randomized study evaluated 297 patients at 104 sites. The study was intended to stop at 200 weeks, but was prematurely terminated at 104 weeks. Infliximab dosing was 5 mg/kg every 8 weeks. This study was called the PREVENT study: Prospective, Multicenter, Randomized, Double-blind, Placebo-Controlled Trial Comparing Remade and Placebo in the Prevention of Surgical Resection Who Are at an Increased Risk of Recurrence.
- At week 76, clinical recurrence was not statistically different, though favored infliximab group: 12.9% vs. 20.0%
- At week 76, endoscopic recurrence was less in infliximab-treated: 30.6% vs 60.0%
- Also, more severe endoscopic recurrence (Rutgeerts scores of i3 or i4) was markedly lower: 22.4% vs 51.3%
- Infliximab effectiveness could have been even higher if there had been an opportunity to escalate dosing; this occurs in about half of patients in typical clinical care.
- This study’s focus on the primary outcome of clinical recurrence winds up overshadowing the much improved endoscopic results.
My take: I think that most well-informed patients and physicians would prefer to be treated post-operatively if they look at the results of this study closely.