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

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.