More Lessons in TNF Therapy (Part 1)

More data has been published regarding postoperative therapy with infliximab (IFX) in Crohn’s disease (Clin Gastroenterol Hepatol 2014; 12: 1494-1502, editorial 1503-6).

In this prospective, open-label study with at least 5 years of followup, 24 patients who were previously randomly assigned to receive IFX or placebo for 1 year after ileocolonic resection were given the option of continuing IFX or stopping IFX (“watch and wait approach”).  This was a strange study and perhaps mirrors clinical experience in that consistent usage of IFX was not maintained in the majority; in addition, there was not a set pattern with regard to thiopurine usage.

Of 11 patients who received IFX during the first year after surgery, 8 elected to stop IFX and all 8 experienced endoscopic recurrences at a mean of 18.2 months, including 5 who needed surgery.  Of 13 patients who received placebo during the first year after resection, 12 elected to initiate IFX at 1-year entry point;  7 of those responded with endoscopic remission. Overall, the mean percentage of time that a patient received IFX was similar between those initially assigned to IFX or placebo (50.3% vs. 53%).

Key findings:

  • Among those originally assigned to the IFX group, there was a longer mean time to first endoscopic recurrence (1231 days vs. 460 days in placebo group).
  • Colonoscopy identified recurrent disease in 22.2% of patients receiving IFX compared with 93% off IFX.  That is, throughout the study there were 84 colonoscopies.  If one was receiving IFX at the time of the colonoscopy, the adjusted rate ratio for being in remission while on IFX was 13.47.
  • Among patients who received IFX for at least 60% of the full study period, they had fewer surgical recurrences: 20.0% compared with 64.3% (5 of 8).
  • Recurrence was similar for patients receiving IFX monotherapy or in combination (though small numbers preclude a definitive assessment).
  • None of the three patients who continued IFX from the beginning have required an operation in the past 8 years.

One can speculate that the main reason why so many placebo-treated patients (12 of 13) elected to start IFX was that there was evidence of recurrent disease; conversely, many of the patients who received IFX postoperatively were in remission and opted for a watch-and-wait approach subsequently.

Study limitations: small numbers, open-label design, changes in therapy at patient’s physician discretion, and no restrictions on use of concomitant medications.

The associated editorial recommends the use of IFX postoperatively in high-risk patients (perforating disease, smokers, >1 surgical resection) and notes that therapy should be started 2-4 weeks after surgery because IFX is “less effective in preventing medical recurrence if started after endoscopic recurrence.”  The editorial suggests that low-risk patients should undergo a 6- to 12-month endoscopic evaluation.  Though, “we urgently need data from large prospective studies such as the PREVENT trial” (NCT01190839) as well as the POCER study.

Bottomline: Infliximab, administered within 4 weeks of an ileocolonic resection, reduces postoperative recurrence of Crohn’s disease and helps prevent further surgeries.  Studies (like this one) with long followup are essential to determine the effectiveness of anti-TNF (tumor necrosis factor) therapies.  It remains unclear whether only “high-risk” patients should receive anti-TNF therapy or whether these agents should be used more broadly.

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