Risk of post-operative complications associated with anti-TNF therapy in inflammatory bowel disease

Table 1 Crohn’s disease study characteristics

Author study center	Study design	Total patients	Study endpoints	Concomitant medication	Case (%)	Control (%)	P value	IFX dosing	Last dose IFX prior to surgery < 12 wk (%)
Marchal[22], 2004, Belgium	Case-control	79 total, 40 cases, 39 controls	Early (10 d) and late (3 mo) complications	5-ASA	30	54	N.S.	Episodic 100%	78
				6MP/AZA	45	26	N.S.
				Steroids	73	41	< 0.00017
				Antibiotics	25	28	N.S.
Colombel[23], 2004, Mayo Clinic, Rochester	Retrospective	270 total, 52 cases	Early (30 d) septic and non-septic complications	5-ASA	-	-	-	Episodic 80%	96
				6MP/AZA	7	-	-
				Steroids	7	-	-
				Antibiotics	-	-	-
Appau[24] , 2008, Cleveland Clinic, Cleveland	Case-control	458 total, 329 Non IFX, 60 IFX, 69 pre IFX	30 d post-operative complications	5-ASA	60	58	0.95	-	100
				6MP/AZA	62	15	< 0.001
				Steroids	65	77	< 0.052
				Antibiotics	-	-	-
Kunitake[29], 2008, Massachusetts General Hospital, Boston (combined study)	Case-control	413 total, 101 cases, 312 control	Post-operative complications	5-ASA	-	-	-	-	100
				6MP/AZA	37	6	0.04
				Steroids	75.30	77	0.79
				Antibiotics	-	-	-

IFX: Infliximab; 5-ASA: 5-aminosalicylic acid; AZA: Azathioprine; 6MP: 6-mercaptopurine; N.S.: Not significant.

Table 2 Complications defined in crohn’s disease

Study	Study endpoints	Infectious	Non-infectious	Major	Minor
Marchal[22]	Early (10 d) and late (3 mo) complications	Catheter sepsis, wound, upper respiratory, Diarrhea,yeast		Sepsis, leak, peritonitis, abscess, wound failure, severe anemia, bulbar ulcer bleeding	Hematoma, fever, delayed transit, mild infection, intestinal obstruction
Colombel[23]	Early (30 d) septic and non septic complications	Wound sepsis, leak, abscess, fistula, sepsis, pneumonia, bacteremia, urosepsis	CD recurrence, small bowel obstruction, GI bleeding, thromboembolism
Appau[24]	30 d post-operative complications	Wound infection, sepsis, intra abdominal abscess, 30 d mortality, readmission rate, anastomotic leak and wound complications
Kunitake[29] (combined study)	Post-operative cumulative complications	Infections, hypomotility, thrombotic, cardiac complications, hepato-renal complications, anastomotic leak, bleeding and death

CD: Crohn’s disease; GI: Gastrointestinal.

Table 3 Post-operative risks of complications with Crohn’s disease

Authors	Complications	Cases (%)	Controls (%)	Risks of complications, OR (95% CI)
Marchal[22]	Early Minor (10 d)	15	13	1.2 (0.3-4.3)
	Late Minor (3 mo)	2.50	5.10	1.1 (0.3-4.0)
	Early Major (10 d)	12.50	7.70	1.7 (0.3-7.7)
	Late Major (3 mo)	17.50	12.80	1.4 (0.4-5.0)
Colombel[23]	Septic	17		0.9 (0.4-1.9)
	Non-septic	23		1.0 (0.5-2.0)
Appau[24]	30 d readmission	20	9.4 + 2.9	2.3 (1.0-5.3)
	30 d sepsis	20	9.7 + 5.8	2.6 (1.1-6.1)
	30 d intra-abdominal abscess	10	4.3 + 4.3 (Non IFX + pre IFX group)	5.8 (1.7-19.7)
Kunitake[29] (combined study)	Post-operative cumulative complications	16.80	15.70	1.1 (0.6-2.0)

IFX: Infliximab; OR: Odd ratio; CI: Confidence interval.

Table 4 Ulcerative colitis study characteristics

Author and study center	Study design	Total patients	Study endpoints	Concomitant medication	Case (%)	Control (%)	P value	IFX dosing	Last dose of IFX prior to surgery < 12 wk
Selvasekar[25], 2007, Mayo Clinic, Rochester	Case-control	301 patients, 47 cases, 254 controls	Post-operative pouch specific and infectious complications	5-ASA	100	60	< 0.0001	Scheduled (majority)	49% (< 8 wk)
				6MP/AZA	91	44	< 0.0001
				Steroids	47	77	< 0.001
				Steroids + AZA	70	21	< 0.001
Schluender[26], 2007, Cedars-Sinai LA	Case-control	151 patients, 17 cases, 134 controls	30 d post-operative surgical and medical complications	5-ASA	-	-	-	2 infusions (median)	Majority (8 wk median)
				6MP/AZA	94	44	0.03
				Steroids	100	100	1
Mor[27], 2008, Cleveland Clinic	Case-control	92 patients, 46 cases, 46 controls	Early (30 d) and late post-operative complications	5-ASA	-	-	-	3 infusions (median)	Majority (13.5 wk median)
				6MP/AZA	39	28	0.27
				Steroids	2 ( ranked dose score)
						2.24	0.42
Ferrante[28], 2009, Belgium	Case-control	141 patients, 22 cases, 119 controls	Early (30 d) post-operative complications	5-ASA				Scheduled 2.5 Infusions (median)	Majority (3.9 wk median)
				6MP/AZA	59	55	0.7
				Steroids (high dose)	9	25	0.163
Kunitake[29], 2008, Massachusetts General Hospital, Boston (combined study)	Case-control	413 total, 101 cases, 312 control	Post-operative complications	5-ASA	-	-	-	-	100%
				6MP/AZA	37	26	0.04
				Steroids	75.30	77	0.79
				Antibiotics	-	-	-

IFX: Infliximab; 5-ASA: 5-aminosalicylic acid; AZA: Azathioprine; 6MP: 6-mercaptopurine.

Table 5 Complications defined in ulcerative colitis studies

Study	Study Endpoints	Infectious	Medical	Surgical	Pouch
Selvasekar[25]	Post-operative pouch specific and infectious complications	Pouch complications plus; wound infections			Anastomotic leak; pelvic abscess
Schluender[26]	30 d post-operative surgical and medical complications	Not defined	Major: pneumonia, DVT, pancreatitis, ARF, CVA; minor: dehydration, thrombophlebitis, pyoderma gangrenosum, urinary retention	Major: SBO, abscess, bleeding, leak; minor: wound infection, ileus, bleeding
Mor[27]	Early (30 d) and late post-operative complications	Early: pelvic sepsis, bleeding, thrombosis, ileus; Late: pouchitis, SBO, stricture
Ferrante[28]	30 d post-operative complications	Surgical infections: pouch complications plus wound infection; non surgical: UTI and respiratory infections			Anastomotic leak; pelvic abscess
Kunitake[29] (combined study)	Post-operative cumulative complications	Infections, hypomotility, thrombotic, cardiac complications, hepato-renal complications, anastomotic leak, bleeding and death

DVT: Deep vein thrombosis; ARF: Acute renal failure; CVA: Cerebrovascular accident; SBO: Small bowel obstruction; UTI: Urinary tract infections.

Table 6 Post-operative risks of complications with ulcerative colitis

Authors	Complications	Cases (%)	Controls (%)	Risks of complications, OR (95% CI)
Selvasekar[25]	Pouch specific	19	7	2.6 (0.9-7.5)
	Infectious	28	10	2.7 (1.1-6.7)
Schluender[26]	Medical	6	10	0.6 (0.1-4.8)
	Surgical	30	18	1.9 (0.6-5.9)
	Infectious	18	8	2.4 ( 0.6-9.6)
Mor[27]	Early	35	15	3.5 (1.5-8.3)
	Late	52	37	2.2 (0.9-5.3)
	Sepsis	22	1	13.8 (1.8-105)
Ferrante[28]	Pouch specific	0	17	0.9 (0.8-0.9)
	Surgical infections	11	23	0.2 (0.03-1.6)
	Total Infectious	11	28.60	0.3 (0.07-1.4)
Kunitake[29] (combined study)	Post-operative cumulative complications	16.80	15.70	1.1 (0.6-2.0)

OR: Odd ratio; CI: Confidence interval.