133defunctionalizing proximal stoma to reduce postoperative complications.
Considering penetrating disease as a predictor in the study for increased intra-
abdominal infectious complications, the authors suggest that the presence of fis-
tula or abscess may be the most important influence for development of
complications [ 9 ].
From the above studies, consequences of anti-TNF agents on postoperative com-
plications in Crohn’s disease remained controversial. Therefore, a meta-analysis
was conducted through a literature database between 1966 and September 2011,
observing 30-day overall complication rates and infectious and noninfectious com-
plications between patients exposed to anti-TNF agents and those who were not
[ 10 ]. Infectious complications were broken down into either anastomosis related
(abscess, anastomotic leak, or fistula) or other, likewise, noninfectious categorized
into intestinal obstruction/prolonged ileus, thromboembolic events, gastrointestinal
bleeding, cardiovascular, respiratory, and renal impediments. Heterogeneity was
considered significant if a chi-squared test measured a p-value <0.1 or an I^2 >50%.
After applying the exclusion criteria, 8 studies remained with a total of 1641
participants with 423/1641 (25.8%) exposed to anti-TNF agents. All studies utilized
infliximab except one that included adalimumab and certolizumab pegol.
Investigating infectious complications, six studies were pooled revealing an OR of
1.50 (95% CI, 1.08–2.08, I^2 = 43.0%), supporting clinical significant relationship
between preoperative infliximab and postoperative infectious complications
(Table 9.1). When results were pooled, overall adverse effects demonstrated a trend
for increased risk and however lacked clinical significance (OR 1.72, 95% CI 0.93–
3.19, I^2 = 76.1%) with a consistent finding after removing three lower-quality stud-
ies although there was significant heterogeneity (Table 9.2). A similar trend was
seen in noninfectious complications; however, statistical significance was not
reached (OR 2.00, 95% CI 0.89–4.46, I^2 = 52.7%). Given these findings and overall
trend in higher risk of postoperative complications, the authors concluded that sur-
gery in patients exposed to anti-TNF agents increased their risk of adverse effects;
thus, elective surgery should be scheduled distant from anti-TNF therapy, although
the ideal last dose date remained undefined [ 10 ].
Table 9.1 Meta-analysis: pooled infectious complications in infliximab preoperatively with
Crohn’s disease
Study Infliximab (n) Non-infliximab (n) Total (n) Odds ratio
Appau et al. [ 8 ] 60 329 389 2.93 (1.63–5.27)
Canedo et al. [ 11 ] 65 160 225 1.19 (0.58–2.42)
Kasparek et al. [ 12 ] 48 48 96 1.00 (0.44–2.29)
Marchal et al. [ 13 ] 40 39 79 2.27 (0.70–7.38)
Tay et al. [ 14 ] 22 78 100 1.38 (0.33–5.72)
Colombel et al. [ 15 ] 52 218 270 0.85 (0.39–1.88)
Total 287 872 1159 1.50 (1.08–2.08)Test for heterogeneity: X^2 = 8.78, df = 5 (p = 0.12), I^2 = 43.0%
Adapted from Kopylov et al. [ 10 ]
9 Use of Biologics in Crohn’s Disease and Ulcerative Colitis Prior to Surgery