Mucosal healing in inflammatory bowel disease: Maintain or de-escalate therapy

Table 2 Studies concerning withdrawal of immunomodulators

Ref.	Design	Disease n. patients	Intervention	Surveillance	Evaluation	Main outcome	Results	Predictive factors
Fraser et al[65]	RA, sc	272 CD	Continue AZA vs discontinue AZA	-	Clinical assessment	Cumulative remission rate	At 1 yr 95% vs 63%,	Risk factors for relapse: Female sex (only CD) and higher WBC; no differences for treatment duration of AZA
		346 UC					at 2 yr 90% vs 44%,
							at 3 yr 69% vs 34%,
							at 4 yr 63% vs 28%,
							at 5 yr 62% vs 25%
Lobel et al[66]	RA, sc	61 UC	Continue 6-MP vs discontinue 6-MP	Median f-u: 40 mo (range 4-344)	Clinical and endoscopic assessment	Median time to relapse (wk)	58 wk vs 24 wk	No significant risk factors for relapse were found
							Relapse at 1 yr: 43% vs 77%
Lémann et al[67]	RCT, db, mc	83 CD	Continue AZA vs placebo	18 mo	Clinical assessment	Relapse rate	8% vs 21%	Risk factors for relapse: CRP > 20 mg/L, time steroid-free < 50 mo, Hb < 12 g/dL
Van Assche et al[73]	RCT, db, mc	80 CD	Continue IFX + IS vs IFX + stop IS	104 wk	Clinical and endoscopic assessment	Median CRP;	1.6 mg/L vs 2.8 mg/L;	Not significant P-value for endoscopic features in either groups
						Median TL;	2.8 μg/mL vs 1.6 μg/mL;
						Median SES-CD;	1 vs 2.5
						AE rate;	7.5% vs 7.5%;
						12-mo relapse	58% vs 72.7%
Cassinotti et al[68]	RA, mc	127 UC	AZA discontinuation	Median f-u: 55 mo (range 1-182)	Clinical assessment	Cumulative relapse rate	At 1 yr 35%,	Risk factors for relapse: Short treatment duration of AZA
							at 2 yr 49%,
							at 3 yr 59%,
							at 4 yr 61%,
							at 5 yr 65%
Treton et al[69]	PA, mc	66 CD	AZA discontinuation	Median f-u: 54 mo	Clinical assessment	Cumulative relapse rate	At 1 yr 14%,	Risk factors for relapse: Higher WCB count
							at 3 yr 53%,
				(IQR 20-69)			at 5 yr 62%
Kennedy et al[70]	RA, mc	129 CD	Thiopurine discontinuation	12 mo and 24 mo	Clinical assessment	Cumulative relapse rate	CD at 12 mo: Severe 8.5%, moderate 14%; at 24 mo: Severe 12%, moderate 27%.	Risk factors for relapse: Elevated CRP (only in CD), higher WBC count (only in UC)
		108 UC					UC at 12 mo: Severe 0%, moderate 12%; at 24 mo: Severe 3%, moderate 22%
Moreno-Rincón et al[71]	RA, mc	102 UC	Thiopurine	Median f-u: 27 mo (IRQ 9-75)	Clinical assessment	Cumulative relapse rate	At 1 yr: 18.8%,	Risk factors for relapse: Biological remission, thiopurine treatment duration, pancolitis, time from diagnosis until the starting of thiopurines, number of relapse before the withdrawal
			discontinuation				at 3 yr: 36.5%,
							at 5 yr: 43%
Qiu et al[72]	PA, sc	109 CD	Thiopurine	Median f-u: 46 mo (IQR 27-67)	Clinical and endoscopic assessment	Cumulative relapse rate	45% endoscopic flare, 37% clinical flare, 16% surgery, 23% hospitalization	Risk factors for relapse: Prior bowel complication, perianal disease at diagnosis, CRP > 3 mg/L
			discontinuation

RCT: Randomized controlled trial; UC: Ulcerative colitis; CD: Crohn’s disease; mc: Multicenter; db: Double-blind; sc: Single-centre; AZA: Azathioprine; RA: Retrospective analysis; PA: Prospective analysis; IRQ: Interquartile range; CRP: C-reactive protein.