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

Table 1 Studies concerning the achievement of mucosal healing

Ref.	Design	No. of patients	Drugs (dose)	Time of endoscopy	Endoscopic index	Definition of MH	Results
5-ASA
Vecchi et al[43]	RCT, mc	130 UC	5-ASA 4 g p.o. vs 2 + 2 g and enema	6 wk	Rachmilewitz	< 4	58% vs 71%
Mansfield et al[44]	RCT, db, mc	50 UC	Balsalazide 6.75 g vs SASP 3 g	8 wk	4 point score	Score 0	27% vs 25%
Kruis et al[45]	RCT, db, mc	321 UC	5-ASA 0.5 g × 3 vs 1 g × 3 vs 1.5 g × 3	8 wk	Rachmilewitz	Histology improvement	53% vs 84% vs 70%
Hanauer et al[47]	RCT, db, mc	391 UC	Asacol 4.8 g vs 2.4 g	6 wk	No score	Normal endoscopy	84% vs 67% (in moderate UC)
ASCEND 1 and 2
Kamm et al[48]	RCT, db, mc	343 UC	Mesalamine MMX 4.8 g vs 2.4 g vs plc	8 wk	Mod. Sutherland index	< 1	77% vs 69% vs 46%
MMX
Kruis et al[46]	RCT, db, mc	380 UC	5-ASA 3 g vs 1 g × 3	8 wk	Rachmilewitz	< 4	71% vs 70%
Steroids
Ardizzone et al[49]	RA, sc	157 UC	Systemic steroids 40-60 mg	3 mo	Mod. Baron score	Score 0	38%
Sandborn et al[50]	RTC, db, mc	672 UC	Budesonide MMX 9 mg vs 6 mg vs plc	8 wk	UCDAI mucosal appearance	0	27% vs 16% vs 17%
CORE
Van Assche et al[51]	RTC, db, mc	282 UC	BDP 5 mg/d vs PD 40 mg/d (tap.)	4 wk	DAI subscore	0	23% vs 21%
Immunomodulators
D’Haens et al[60]	PA, sc	15 CD	AZA 2 mg/kg	26 wk	Rutgeerts score	Ri 0	40%
Ardizzone et al[52]	RCT, sc	72 UC	5-ASA vs AZA	3 mo and 6 mo	Baron score	Improving mean Baron index	At 3 mo: 2.3 vs 1.1
							at 6 mo: 2.2. vs 0.9
Mantzaris et al[61]	RCT, sc	57 CD	AZA 2-2.5 mg/kg vs budesonide 6-9 mg	52 wk	CDEIS	CDEIS < 4	83% vs 24%
Laharie et al[62]	RTC, sc	51 CD	MTX 15-25 mg/wk vs AZA 2-3 mg/kg vs IFX 5 mg/kg		CDEIS	CDEIS < 4	11% vs 50% vs 60%
Rispo et al[53]	PA, sc	104 UC	AZA or 6-MP	104 wk	Mayo	Mayo 0-1	36%
Biologics
Colombel et al[63]	RCT, db, mc	508 CD	AZA 2.5 mg/kg vs IFX 5 mg/kg vs AZA 2.5 mg/kg + IFX 5 mg/kg	26 wk	No score	Absence of ulcers	16% vs 30% vs 44%
SONIC
Reinisch et al[54]	RCT, db, mc	390 UC	ADA 160/80/40 mg vs 80/40 mg vs plc	8 wk	Mayo	Mayo 0-1	47% vs 37% vs 41%
ULTRA 1
Sandborn et al[55]	RCT, db, mc	518 UC	ADA 160/80/40 mg vs plc	8 wk and 52 wk	Mayo	Mayo 0-1	18% vs 10% (Sustained MH)
ULTRA 2
Rutgeerts et al[64]	RCT, db, mc	135 CD	ADA only induction (plc in maintenance) vs ADA continuous	12 wk and 52 wk	CDEIS	CDEIS 0	Baseline CDEIS ≤ 9: Continuous at 12 wk 40%, at 52 wk 30%.
EXTEND
							Baseline CDEIS < 9: Continuous at 12 wks 16% at 52 wk 19%
Laharie et al[58]	RA, mc	63 UC	IFX 5 mg/kg	6-52 wk	Mayo	Mayo 0-1	48%
Feagan et al[56]	RCT, db, mc	746 UC	Vedolizumab every 8 wk vs Vedolizumab every 4 wk vs plc	6 wk and 52 wk	Mayo	Mayo 0-1	6 wk: VDZ 41% vs placebo 24%;
GEMINI							52 wk: 56% vs 51% vs 20%
Sandborn et al[59]	RCT, db, mc	774 UC	Golimumab 400/200 mg vs 200/100 mg vs plc	6 wk	Mayo	Mayo 0-1	17.9% vs 17.8% vs 6.4%
PURSUIT

RCT: Randomized controlled trial; MH: Mucosal healing; 5-ASA: 5-aminosalicylic acid; mc: Multicenter; db: Double-blind; sc: Single-centre; RA: Retrospective analysis; AZA: Azathioprine; CDEIS: Crohn’s Disease Endoscopic Index of Severity; UC: Ulcerative colitis; CD: Crohn’s disease; MMX: Multi Matrix System; IFX: Infliximab; MTX: Methotrexate; PA: Prospective analysis; BDF: Beclomethasone dipropionate.