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healing, TNF-α stimulates fibroblast proliferation and recruitment into the wound.
These functions contribute to the role in angiogenesis and collagen synthesis.
Inhibition of this function by infliximab and similar agents can play a role in tissue
repair and wound healing, possibly impacting postsurgical outcomes [ 3 , 4 ]. Fourth,
TNF-α protects against infections, shown in TNF-deficient mice who were more
prone to infections [ 6 ]. Inhibiting this function increases risk for opportunistic
infections, pneumonia, and sepsis by decreasing both polymorphonuclear cells and
T-lymphocytes. As one can imagine, this makes prescribers wary of the safety of
biologic therapy in the perioperative setting.
In 1998 the FDA approved infliximab for the treatment of Crohn’s disease which
has become an important agent for the induction and maintenance of clinical remis-
sion. Specifically infliximab has shown value as a steroid-sparing agent and success
in closure of enterocutaneous, perianal, and rectovaginal fistulas and maintaining
fistula closure [ 7 ]. Although infliximab has shown to be effective in controlling
Crohn’s disease, the reality is 75% eventually undergo surgery for complicating or
refractory disease. Considering the bulk of patients that are exposed to biologic
therapy prior to surgery, numerous studies have investigated the perioperative risk
in both Crohn’s disease and ulcerative colitis.
At the Cleveland Clinic, 30-day mortality, wound infection/complications, anas-
tomotic leak, sepsis, intra-abdominal abscess, and readmission rates were measured
through contemporary and historical cohorts between 1998 and 2008 on Crohn’s
disease patients exposed to infliximab within 3 months of an ileocolonic resection
[ 8 ]. Sixty patients exposed to infliximab were compared to 329 contemporary cohort
undergoing ileocolonic resections without prior IFX exposure. The protocol
excluded ulcerative colitis and indeterminate colitis and patients with infliximab
exposure greater than 3 months before surgery. The type of surgery included an
ileocolonic resection; additional procedures such as strictureplasty, small bowel or
colonic resections, or prior GI surgeries were excluded.
Results of the study revealed an increased risk with infliximab and 30-day post-
operative readmissions (adjusted OR, 2.3 [1.02–5.33], p = 0.045), sepsis (adjusted
OR, 2.62 [1.12–6.13], p = 0.027), and intra-abdominal abscesses (adjusted OR, 5.78
[1.69–19.7], p = 0.005). On review it was noted that concomitant use of immuno-
suppression was higher in the infliximab group (61.7% vs. 16.7%; p = 0.001),
whereas steroid use was higher in the non-infliximab group (76.9% vs. 65%,
p = 0.05). Despite the latter having a higher incidence of corticosteroid exposure,
the rate of adverse postsurgical outcomes appeared higher in the infliximab-treated
arm. In further evaluating timing of infliximab and if 2 vs. 3 months of exposure
changed outcomes, the authors took a subset of patients receiving the biologic agent
within two months of surgery and studied outcomes after ileocolonic resection. No
difference was seen in these subsets. Given TNF-α functions as a potent inflamma-
tory mediator that delays wound healing, the discussion puts no surprise to the
increased incidence of sepsis and abscesses with infliximab prior to surgery. The
author’s consensus was the use of infliximab 3 months prior to ICRA increased risk
of 30-day postoperative intra-abdominal abscesses, sepsis, anastomotic leaks, and
readmission rates [ 8 ].
A. Kamal and B. Lashner