Predictors of recurrence of Crohn’s disease after ileocolectomy: A review

Table 1 Types of postoperative recurrence and evaluation type

Type of recurrence	Evaluation method
Clinical	Questionnaire, CDAI, Harvey-Bradshaw Index, IBDQ
Endoscopic	Rutgeerts score, Crohn’s disease endoscopic index of severity
Radiographic	CT or MR enterography, barium enema small bowel follow through
Serological	Measurement of CRP and ESR
Surgical	Requirement for repeat surgery

CDAI: Crohn’s disease activity score; IBDQ: Inflammatory Bowel Disease Questionnaire; CT: Computed tomography; MR: Magnetic resonance; CRP: C reactive protein; ESR: Erythrocyte sedimentation rate.

Table 2 Factors in the Crohn’s disease activity score

General well-being

Number of stools/d

Abdominal pain

Weight loss

Presence of arthralgia, fistuli, fever and/or ocular, dermatological or anal manifestations

The need for anti-diarrheal medication

Abdominal mass

Hematocrit

Based on patient symptoms during the 7 d prior to taking the survey.

Table 3 Factors in the Rutgeerts endoscopic recurrence score for postoperative recurrence of Crohn’s disease in the distal ileum

Endoscopic appearance	Score
No aphthous ulcers	0
< 5 aphthous ulcers	1
> 5 aphthous ulcers with normal mucosa between the ulcers	2
Diffuse aphthous ulcers throughout the ileum with intervening inflamed mucosa	3
Large ulcers with diffuse inflammation, nodules or narrowing of the ileum	4

Table 4 Overall recurrence rates by post ileocolectomy follow up and type of recurrence

Time post ileocolectomy	Type of recurrence	% of ileocolectomy Patients	Ref.
1 yr	Clinical	0%-44%	McLeod et al[61], Walters et al[10], Aratari et al[27], Bordeianou et al[14], Sorrentino et al[28], Pascua et al[53]
	Endoscopic	0%-84%	Bordeianou et al[14], Walters et al[10], McLeod et al[15,61], Regueiro et al[16,82], Rutgeerts et al[11], Pascua et al[53], Domènech et al[80], Sorrentino et al[28], Meresse et al[40], Lasson et al[89]
	Surgical	4%-25%	Aratari et al[27], Iesalnieks et al[57]
5 yr	Clinical	32%	Aratari et al[27]
	Endoscopic	55%-77%	Bordeianou et al[14], McLeod et al[15], Yamaoto et al[42]
	Symptomatic	50%	Bordeianou et al[14]
	Surgical	4%-25%	Bordeianou et al[14], Aratari et al[27], Riss et al[56], Yamamoto et al[42]
10 yr	Clinical	52%	Aratari et al[27]
	Endoscopic	74%	Malireddy et al[17], Bordeianou et al[14]
	Surgical	12%-57%	Stocchi et al[18], Aratari et al[27], Riss et al[56], Iesalnieks et al[57]

Table 5 Effect of smoking on postoperative recurrence

Association	Number and type of patients	Ref.
Recurrent clinical symptoms (OR = 2.96)	59 patients post colonic resection for CD (not only ileocolectomies)	Kane et al[22]
Shorter duration to clinical relapse (104 wk shorter)
Recurrent clinical symptoms (worse CDAI scores)	182 post colonic resection for CD (not only ileocolectomies)	Cottone et al[23]
Increased rates of endoscopic recurrence
Increased likelihood of requiring surgery
Smoking at the time of the 1st ileocolectomy conferred a 2.1 fold increased likelihood of requiring another operation	176 post ileocolectomy patients with at least 1 recurrence	Unkart et al[21]
OR of 2.2 for clinical recurrence	Meta-analysis of 16 studies, 2962 patients	Reese et al[24]
Increased risk of surgical recurrence particularly at 10 years (OR = 2.6)
Smokers had a lower 5 and 10-yr recurrence free likelihood (65 and 45% vs 81 and 64% in nonsmokers)	141 ileocolectomy patients	Yamamoto and Keighley[26]
Recurrence free rates were lower in those that smoked > 15 cigarettes per day
Patients that quit smoking are less likely to require redo ileocolectomy	266	Ryan et al[25]
No association with recurrence	89 lap ileocolectomy patients	Malireddy et al[17]
No association with clinical or surgical recurrence	83	Aratari[27]
No association with clinical or endoscopic recurrence	43 resections (30 = Ileocolectomies)	Sorrentino[28]

CD: Crohn’s disease; CDAI: Crohn’s disease activity score.

Table 6 Key studies on medical treatment for the prevention of postoperative recurrence in post ileocolectomy patients

Interventions Compared	Study Design	Study Numbers (end of follow-up)	Follow-up	Clinical Improvement	Endoscopic Improvement	Other	Ref.
Mesalamine vs Placebo	Double Blind, Multicenter	87	12 mo	59% of placebo vs 41% of mesalamine had a clinical relapse	Significantly less severe and less frequent lesions in mesalamine group (P < 0.008)	Severe endoscopic or radiologic was 24% in mesalamine vs 56% of placebo (P = 0.004)	Brignola et al[68]
Budesonide vs placebo	Double-blind, randomized trial	129	12 mo	No difference in CDAI at any time point in the study	Only patients who underwent surgery for increased disease symptoms (not fibrostenotic or fistulizing disease) had a significantly lower endoscopic recurrence rate (32% vs 65% of the placebo group)	AT 12 mo the ESR value was 13.3 mm/h in the budesonide group vs 20.2 mm/h in the placebo group (P = 0.017). Mean CRP values after decreased from 19.0 to 6.2 mg/L in the budesonide group and from 12.7 to 12.2 mg/L in the placebo group (P = 0.018)	Hellers et al[64]
Mesalamine vs placebo	Double-blind, placebo controlled12	246	48 wk	25% of the mesalamine vs 36% of the placebo had a relapse [(per CDAI) P = 0.06] On subgroup analysis ileocolonic patients had fewer relapses on mesalamine (21% vs 41%) P = 0.003		10% vs 23% surgical recurrence (P = 0.13)	Sutherland et al[67]
Mesalamine vs placebo	Randomized	163 post-surgical patients1 109 were post ileocolectomy	Maximum 72 mo		Endoscopic and radiological recurrence was significantly decreased in the mesalamine group with relative risks of 0.6 (P = 0.016)	31% symptomatic recurrence rate (symptoms plus endoscopic and/or radiological confirmation of disease) vs 41% in the control group, P = 0.03	McLeod et al[69]
6 MP, mesalamine or placebo	Multi (5) center, double blind, randomized	131	24 mo	Clinical recurrence was improved by mesalamine or 6 MP. Clinical recurrence rates at 24 mo were 50% for 6 MP, 58% for mesalamine and 77% for placebo (P = 0.04)	Only 6 MP, not mesalamine was superior to placebo to prevent endoscopic and radiographic recurrence at 24 mo. Relapse was 43% with 6 MP, 63% with mesalamine, 64% with placebo (P = 0.03)	Radiographic recurrence rates were 33% for 6 MP, 46% for mesalamine and 49% for placebo (P > 0.05)	Hanauer et al[76]
Infliximab vs mesalamine (control)	Prospective, multicenter pilot study to determine if giving infliximab after diagnosis of postoperative endoscopic ileocolic CD recurrence at 6 mo can induce endoscopic remission at 54 wk	24 (19 had ileocaecal disease)	54 wk	No clinical recurrence in the infliximab group at 6 mo	No endoscopic remission at 54 wk in the mesalamine group vs the infliximab group 54% had endoscopic remission at 54 wk (P = 0.01)		Sorrentino et al[28]
				18% of mesalamine who had clinical relapse by 9 mo
Adalizumab vs AZA vs mesalamine	Randomized	51	2 yr		The ADA treated patients had the lowest incidence of endoscopic recurrence (6.3% vs 64.7% of the AZA group and 83.3% of the mesalamine group)		Savarino et al[83]
Infliximab vs placebo	Randomized	24	1 yr	Clinical remission was higher in the IFX group (80% vs 54%) but P = 0.38)	Endoscopic and histologic recurrence was significantly lower at 1 yr in the patients treated with infliximab (1 of 11; 9.1% and) vs placebo (11 of 13 patients; 84.6%). P = 0.0006	Lower histologic recurrence in the IFX group (3 of 11/27% vs 11 of 13/85% of placebo) P = 0.01	Regueiro et al[82]
Metronidazole +AZA or placebo	62	Randomized	12 mo	Endoscopic recurrence was observed in 14 of 32 (43.7%) patients in the AZA group and in 20 of 29 (69.0%) patients in the placebo group at 12 mo post-surgery (P = 0.048. At 1 yr 21% of the AZA group were lesion free vs 3% of the placebo (P = 0.04)			D'Haens et al[77]
Metronidazole vs placebo	Double-blind controlled	51	3 yr	Clinical recurrence rates at 1 yr were 4% in the metronidazole vs 25% of placebo) NSD P = 0.04. Reductions at 2 yr (26% vs 43%) and 3 yr (30% vs 50%) both NSD	At 12 wk, 21 of 28 patients (75%) in the placebo group had recurrent lesions in the neoterminal ileum vs 12 of 23 patients (52%) in the metronidazole group (P = 0.09)		Rutgeerts et al[65]
Immunosuppressants (AZA/6 MP or MTX) vs control (5 ASAs or no treatment)		26 patients undergoing their 2nd ileocolectomy	3 yr	Clinical recurrence was lower in the immmunosuppressant group vs the control group (3/12, 25% vs 6/10, 60%; P < 0.05)		The control group required a 3rd resection more commonly. (7/12, 58% vs 2/14, 17% P < 0.02)	Alves et al[79]
			(range 17-178 mo)	No difference in time to recurrence was seen (approximately 27 mo in both groups)
AZA therapy commenced immediatiely post resection	Prospective, observational	56 consecutive patients 15 or 27% had ileocolectomies	Mean 12-84 mo	No clinical recurrence at 12 mo recurrence	70% had endoscopic recurrence at 12 mo. The cumulative probability of endoscopic recurrence was 82% at 5 yr		Domènech[90]

¹Study included non ileocolectomy patients in addition to ileocolectomy patients;

²Study included medically treated patients in addition to ileocolectomy patients. AZA: Azathioprine; 6 MP: 6 mercaptopurine; ASAs: Aminosalicylates.