68
AZA (100–150 mg daily depending on body mass) for 12 months had significantly
less endoscopic recurrence (Rutgeerts i2–i4) at 1 year than metronidazole alone
(43.7% vs. 69.0%, p = 0.048) [ 44 ].
Budesonide has been studied in two controlled trials in prevention of POR. Meta-
analysis of these two studies did not reveal any difference between those treated
with budesonide compared to placebo (mean difference 7.9%, 95% CI 6.0–21.9%,
p = 0.263) [ 45 ].
Biologics for Prevention of POR
There is increasing evidence that biologic agents are the most effective therapy to
prevent POR. The most well-studied agents in this class are the antitumor necrosis
factor alpha (anti-TNFα) agents. The first report of successful use of prophylactic
infliximab (IFX) in a CD colitis patient after a partial colonic resection occurred in
2006 by Sorrentino et al. [ 46 ]. Since this initial description, multiple studies have
focused on the role of anti-TNFs in preventing POR. Regueiro et al. performed the
first randomized, placebo-controlled trial examining the ability of IFX (initiated
within 4 weeks of surgery) to prevent endoscopic recurrence 1 year after ileocolonic
resection [ 47 ]. In this study of 24 CD patients at moderate to high risk for POR,
patients randomized to IFX had significantly lower rates of endoscopic recurrence
compared to placebo (1/11, 9.2% vs. 11/13, 84.6%, p = 0.0006). Following these
patients out to 5 years postoperatively, patients assigned to IFX continued to have
significantly lower rates of endoscopic recurrence (22.2% vs. 93.9%, p < 0.0001)
and longer mean time to first endoscopic recurrence (1231 ± 747 days vs.
460 ± 121 days, p = 0.003) [ 48 ]. Patients who were initially assigned to IFX had
significantly longer time to repeat surgery (1798 ± 359 days vs. 1058 ± 529 days,
p = 0.04). Those who stayed on IFX for a longer period also had significantly lower
rates of surgical recurrence (20.0% vs. 64.3%, p = 0.047) suggestive of a mainte-
nance effect of prophylactic IFX. This effect was further shown by Sorrentino et al.
when patients maintained on IFX (5 mg/kg) for 3 years postoperatively had IFX
stopped [ 49 ]. Of 12 patients who had no evidence of endoscopic or clinical recur-
rence prior to cessation of IFX, 10/12 (83%) developed endoscopic recurrence after
4 months without IFX. Mucosal integrity was restored with retreatment with lower-
dose IFX (3 mg/kg every 8 weeks). Yoshida and colleagues similarly demonstrated
a durable effect of IFX when following 31 postoperative CD patients who were
maintained on 5 mg/kg every 8 weeks IFX (n = 15) or placebo (n = 16). Both arms
received oral mesalamine 1.5 g/day for trial duration. They found significantly
higher rates of maintained clinical, serologic (CRP), and endoscopic remission in
patients treated with IFX than placebo [ 50 ].
In a subsequent follow-up landmark study, Regueiro et al. performed a prospec-
tive, multicenter, randomized, double-blind, placebo-controlled trial comparing
IFX (5 mg/kg every 8 weeks, no induction dosing) to placebo for individuals at
increased risk of POR (PREVENT study) [ 32 ]. In this study, patients were included
B.H. Click and M. Regueiro