72
were initiated on IFX and 11 on mesalamine for 1 year duration. The majority
(54%) of patients treated with IFX had endoscopic remission (<i2), while no mesa-
lamine-treated patients had endoscopic improvement. ADA appears equally effica-
cious in treating early recurrence as shown in the aforementioned study by
Papamichael et al. [ 54 ]. ADA promoted mucosal healing in 60% of treated patients
(n = 15) who had endoscopic disease at 6 months post-resection. Together, these
studies suggest that anti-TNF therapy appears effective in achieving mucosal heal-
ing in patients who develop early postoperative recurrence. Thus, watching and
treating if or when disease recurs are reasonable options in select patients.
Postoperative Prophylaxis
As discussed previously, the immediate postoperative use of multiple medications
can significantly decrease the rates of endoscopic and clinical occurrence with the
largest effect observed in anti-TNF agents.
In a landmark study, the timing of first ileocolonoscopy after surgery to detect
endoscopic recurrence and optimal medical therapy to treat endoscopic recur-
rence was evaluated in the POCER [ 58 ]. The primary outcome of this multicenter,
randomized trial was endoscopic recurrence at 18 months post-resection.
Postoperative CD patients were randomized in a 2:1 fashion to receive colonos-
copy at 6 months (active care) or no 6-month colonoscopy (standard care). All
patients underwent colonoscopy at 18 months postoperatively. Patients were
maintained on postoperative prophylaxis based on risk of recurrence. Patients
were considered high risk if they were active smokers (any number of cigarettes)
and had perforating disease or prior resection. Low-risk patients lacked these fac-
tors. All patients received metronidazole 400 mg twice daily for 3 months postop-
eratively. If not tolerated, dose was decreased to 200 mg twice daily or stopped.
Patients at high risk for recurrence also received AZA 2 mg/kg/day or 6-MP
1.5 mg/kg/day within 1 month of surgery for 18 months. Patients intolerant to
thiopurine were started on ADA (160/80/40 mg induction then 40 mg every
2 weeks) for 18 months. Medical therapy was “stepped up” if there was evidence
of endoscopic recurrence (≥i2) at 6-month colonoscopy. Low-risk patients with
6-month endoscopic recurrence were started on thiopurine therapy. High-risk
patients receiving thiopurine-added ADA induction and maintenance and those
already receiving ADA maintenance were escalated to 40 mg weekly dosing. The
authors found that the 18-month primary endpoint of endoscopic recurrence was
significantly less in the active care arm than the standard care arm (49% vs. 67%,
p = 0.03). Analyzing the immediate use of ADA compared to later ADA addition
to thiopurine therapy at 6 months (in the high-risk cohort) demonstrated no sig-
nificant difference in endoscopic recurrence at 18 months (immediate post-op
commencement, 12/28, 48%; 6-month step-up, 20/33, 61%, p = 0.17). Thus, early
endoscopy with escalation of medical therapy significantly alters the future rates
of endoscopic disease. Furthermore, early endoscopic-guided anti-TNF initiation
B.H. Click and M. Regueiro