71significantly superior. Of the examined treatment modalities, only budesonide (RR
0.93, 95% CI 0.40–1.84) was not significantly better than placebo in preventing
clinical recurrence. Similarly, when evaluating prevention of endoscopic recurrence
(Rutgeerts ≥ i2), antibiotics (RR 0.16, 95% CI 0.15–0.92), immunomodulator
monotherapy (RR 0.33, 95% CI 0.13–0.68), immunomodulator with antibiotics
(RR 0.16, 95% CI 0.04–0.48), and anti-TNF monotherapy (RR 0.01, 95% CI 0.00–
0.05) were significantly better than placebo. For prevention of endoscopic recur-
rence, neither mesalamine (RR 0.67, 95% CI 0.39–1.08) nor budesonide (RR 0.86,
95% CI 0.61–1.22) was significantly different than placebo. The authors concluded
that anti-TNF monotherapy was the most effective pharmacologic intervention for
prophylaxis of POR with large effect sizes relative to all other strategies (clinical
recurrence, RR 0.02–0.20; endoscopic recurrence, RR 0.005–0.04).
The safety of anti-TNF therapy has been demonstrated in several studies.
Regueiro et al. found no increased risk of adverse events in IFX-treated patients
compared to placebo including postoperative complications up to 1 year after sur-
gery [ 56 ]. Similarly, Savarino et al. reported ADA-treated postoperative CD patients
had fewer adverse events than AZA- and mesalamine-treated patients over a 2-year
follow-up period [ 55 ].
To date, no studies evaluating POR using certolizumab pegol, ustekinumab, or
vedolizumab have been reported. The positioning of the anti-interleukin-12/anti-
interleukin- 23 (ustekinumab) and anti-integrin (vedolizumab) in the prevention of
postoperative CD recurrence remains to be determined.
Methods to Treat Postoperative CD Recurrence
Waiting for Recurrence
While postoperative CD recurrence occurs in the majority of patients, it is not ubiq-
uitous. Thus universal postoperative prophylaxis would likely be overtreating a sub-
set of patients, exposing them to unnecessary medications, risks, and expense.
Several studies have shown that anti-TNF agents are capable of inducing remission
in patients who have developed POR. Yamamoto and colleagues studied 26 postop-
erative CD patients who were in clinical remission (CDAI < 150), but at 6 months
post-resection had endoscopic recurrence despite mesalamine (3 g/day) prophylaxis
[ 57 ]. Eight patients were started on IFX (5 mg/kg every 8 weeks), eight patients
received AZA (50 mg/day), and ten were continued on mesalamine (3 g/day). After
6 months, significantly more patients developed clinical recurrence in the mesala-
mine (70%) and AZA (38%) groups than the IFX-treated cohort (0%). Furthermore,
endoscopic improvement was induced in 75% IFX (38% with complete mucosal
healing) compared to 38% AZA (13% complete healing) and 0% mesalamine group
(p = 0.006 improvement, p = 0.10 for complete healing). Similar results were
observed by Sorrentino et al. following 43 postoperative CD patients [ 49 ]. At
6 months post-resection, 24 patients developed endoscopic recurrence (≥i2) and 13
5 Use of Biologics in the Postoperative Management of Crohn’s Disease