Time to clinical response and remission for therapeutics in inflammatory bowel diseases: What should the clinician expect, what should patients be told?

Table 1 Expected time to clinical response for therapeutic agents used in the management of inflammatory bowel disease

Agent	Earliest published clinical response	Earliest published objective response	Time to response in most patients1	Time to futility	Use of therapeutic drug monitoring	Comments
Mesalazine (oral)	1 wk[21]	3 wk[148]	4 wk	> 12 wk	N	A higher dose may lead to a more rapid response
Prednisolone (oral)	2 wk[28]	2 wk[28]	3 to 7 wk	8 wk	N	May take longer for CD
Corticosteroids (IV)	3 d[31]	1 wk[127]	3-5 d	7-10 d	N
Infliximab (IV)	1 wk[48]	8 wk[149]	2-8 wk	> 6 mo	Y
Adalimumab (SC)	4 wk[59]	8 wk[59]	4-8 wk	> 6 mo	Y	Response time better with 160/80 mg vs 40/40 mg induction dosing
Certolizumab (SC)	2wk[61]	10 wk[64]	10 wk	> 16 wk	N
Golimumab (SC)	6 wk[65]	6 wk[65]	6 wk	> 14 wk	Y
Certolizumab (SC)	2 wk[61]	10 wk[64]	10 wk	> 16 wk	N
Vedolizumab (IV)	6 wk[78]	6 wk[78]	19 wk	12 mo	N2	Response time may be better for UC vs CD
Thiopurines (oral)	2 wk[80]	3 mo[88]		> 6-9 mo	Y	Endoscopic response may take much longer than clinical response
			10 to 12 wk
Methotrexate (oral or SC)	9 wk[111]	12 wk[110]	9 wk	> 6 mo	N	Response time and efficacy may be better in 1) CD vs UC, 2) SC vs oral
Cyclosporin (IV then oral)	1 wk[127]	1 wk[127]	4 to 5 d	> 14 d	Y
Tacrolimus (oral)	2 wk[122]	2 wk[122]	2 wk	4 wk	Y
EEN (oral)	10 d[131]	4 wk[139]	3 to 4 wk	8 wk	N

¹Clinical response reported in at least 50% of patients who achieve a response to therapy;

²Therapeutic drug monitoring is not yet widely available. EEN: Exclusive enteral nutrition; IV: Intravenous; SC: Subcutaneous; Y: Yes; N: No; CD: Crohn’s disease; UC: Ulcerative colitis.

Table 2 Previously documented and potential/ novel methods of improving time to response to therapy in Crohn’s disease and ulcerative colitis

	Clinical scenario	Method	Improves time to response	Improves response rate	Improves tolerability	Published data?	Comments	Ref.
Corticosteroids	CD and UC	Intravenous administration		-	-	Yes		[27,32,150]
Anti-tumour necrosis factor-α	Initial or for flare to recapture response (CD and UC)	Addition of azathioprine			-	Yes		[50]
Thiopurine	CD and UC	Addition of allopurinol	-	-		Yes		[105,108]
		Split dosing of thiopurine	-	-		Yes		[151]
Methotrexate	CD	High dose parenteral with corticosteroids if relapse on lower dose	-		-	Yes	Can recapture response	[152]
Tacrolimus	UC	Target levels of 10-15 ng/mL	-		-	Yes		[123]
Aminosalicylates	UC	Maximize dose			-	Yes		[21]
	Distal UC	Choice of formulation (balsalazide)		-	-	Yes		[17,20]

CD: Crohn’s disease; UC: Ulcerative colitis.

Table 3 Factors affecting time to response and response rates of therapies in inflammatory bowel disease

Variable	Parameter	Effect on time to response	Effect on response rate	Medications implicated	Level of evidence1	Ref.
Age	> 65 yr	↑	?	Anti-tumour necrosis factor-α (anti-TNF)	2b	Lobatón et al[143]
Increased body mass index	BMI > 25	-	↓	Azathioprine	2b	Holtmann et al[153]
	Weight > 82 kg	-	↓	Anti-TNF	1b	Reinisch et al[59]
Concomitant therapies		↓	↑	Immunomodulators with anti-TNF	1b	Colombel et al[50]
						Sandborn et al[69]
Smoking status	Current smoker	↑	↓	Anti-TNF	1b, 2b	Arnott et al[154]
						Sandborn et al[69]
Disease duration	> 2 yr	-	↓	Anti-TNF	1b	Colombel et al[155]
						Schreiber et al[156]
						D'Haens et al[157]

¹As per the Oxford level of evidence scoring; The available literature suggests a slower initial response but comparable long-term response rate; The use of “-“ denotes an absence of published data addressing this issue.