Exit strategies in inflammatory bowel disease: Looking beyond anti-tumor necrosis factors

Table 1 Predictive factors for disease recurrence after therapy withdrawal

Poor disease prognostic features	CD/UC: Young age at diagnosis and male sex
	CD: Ileal, colonic or perianal disease; stricturing/penetrating disease
	UC: Pancolitis
Challenging disease control before withdrawal	Many relapses requiring add-on steroids
	Anti-TNF escalation while already on
	Need for surgery or anti-TNF post-operative prophylaxis
Biochemical disease activity	High CRP levels
	Elevated fecal calprotectin
	Elevated white cells or neutrophil count
	Low hemoglobin levels
Endoscopic disease activity	No mucosal healing
Radiological CD activity	No transmural healing
IFX trough levels	High IFX trough levels in monotherapy
	Low IFX trough levels in combination therapy with an imunomodulator

CD: Crohn’s disease; UC: Ulcerative colitis; TNF: Tumor necrosis factor; CRP: C-reactive protein; IFX: Infliximab.

Table 2 Summary of the available evidence for withdrawal of immunosoppressive drugs in inflammatory bowel disease

Drug	Minimum therapy duration before withdrawal, yr	Estimated risk of disease relapse after withdrawal	Therapeutic drug monitoring before withdrawal	Estimated efficacy of re-treatment	De-escalation
Immunomodulators (thiopurine in CD/UC or methotrexate in CD)	3-5	30% by 2, 50%–75% by 5 yr	No data available	75%-90% (often in combination with steroids)	Possible in combination therapy
Anti-TNF	1-2	30%–40% at 6 mo/1 year and > 50% by 2 yr	Possible	80%-90%	Possible (TDM suggested)
Vedolizumab	No data available	65% by 1.5 yr	No data available	50%-65%	No IBD data available beyond 8 wk
Ustekinumab	No data available	59.5% by 1 yr in registrative studies	No data available	39.2%-64% in registrative studies	No IBD data available beyond 12 wk
Tofacitinib	No data available	65 % by 6 mo, 80 % by 1 yr in registrative studies	No data available	75% after 2 months and 50 % after 3 yr in registrative studies	No IBD data available for dosage < 5 mg bid

CD: Crohn’s disease; UC: Ulcerative colitis; TDM: Therapeutic drug monitoring.