Use of methotrexate in inflammatory bowel disease in 2014: A User’s Guide

Table 1 Summary of methotrexate trials in Crohn’s disease

Study		Dose MTX	Route ofadmin	n	Study design	Patients	Duration follow up (wk)	MTX response	MTX remission	Placebo or (Comparator) Response	AE MTX	AE Placebo
Kozarek		25 mg/wk	sq	14	Non-Randomized-open Label	CD	12	79%
Feagan		25 mg/wk	im	141	Double-blind Placebo controlled multi center	Steroid dependent CD	16		39.4%1	19.1%	1%	2%
Oren		12.5 mg/wk	po	84	Randomized Double-Blind Placebo Controlled	Active CD	36		38%	46%
Arora		22.5 mg/wk	po	33	Randomized Double Blind Placebo Controlled	Steroid Dependent CD	52	54%		20%	23%	0
Feagan		15 mg/wk	im	76	Double Blind Placebo Controlled Multi-Center	CD Maintenance	40		65%1	39%	1%	2%
Mate- Jimenez		15 mg/wk	po	38	Randomized Single Center	Steroid Dependent CD	76		80%1 Induction 66.6%1 Maintenance	14% Induction 0 Maintenance	11.5%	0
Lemann		25 mg/wk	im	49	Retrospective	Active CD			84%		49%
Fraser		20 mg/wk (10-25)	po/im	48	Retrospective	Active CD-Maintenance			62%		27%
Ardizzone		25 mg/wk	iv	54	Investigator Blind, randomized	Active CD	24		56%	63% AZA	11%
Mahadevan		25 mg/wk	im	16	Retrospective case series	Fistulizing CD		56%			6%
Wahed		25 mg/wk Induction 15 mg/wk Maintenance	im/po-Induction po-Maintenance	99	Retrospective	AZA Intolerance/ AZA non-responders		62%			8.3%
Feagan		Wk0-10 mg/wk Wk3-20 mg/wk Wk5-25 mg/wk	sq	126	Double Blind Placebo Controlled Multi-center	Active CD	50		IFX + MTX 56%	IFX + PCBO 57%

¹P < 0.05 vs MTX response. MTX: Methotrexate; CD: Crohn’s disease; AE: Adverse events; AZA: Azathioprine.

Table 2 Evidence for induction of remission of ulcerative colitis with methotrexate

Study	Dose (mean)	Route	No. of patients	Study design	Follow-up (wk)	MTX response	MTX remission	Placebo response
Kozarek	25 mg	im	7	Open label	12	5/7 (71.40%)		N/A
Baron	15 mg	Oral	8	Open label	18	3/8 (37.5%)	0	N/A
Oren	12.5 mg	Oral	67	Placebo control	36	14/30 (46.7%)		18/37 (48.6%)
Egan	15 mg 25 mg	scsc	18 12	Open label	16	7/18 (39%) 4/12 (33%)	3/18 (17%) 2/12 (17%)	N/A N/A
Mate-Jimenez	15 mg	Oral	34	6-MP control	30		7/12 (58.30%)	11/14 (78.6%)
Paoluzi	12.5 mg	im	10 thiopurine resistant/intolerant	Open label	26	10/10 (100%)	6/10 (60%)	N/A
Cummings	19.9 mg mean	Oral	11 AZA failure 31 AZA intolerant	Retrospective	30	3/11 (27%) 18/31 (58%)	14/31	N/A
Nathan	20-25 mg	sc/ oral	23	Retrospective	N/A		11/23 (48%)	N/A
Wahed	10-25 mg	Oral, sc	9 thiopurine ineffective 23 thiopurine intolerant	Retrospective	26	7/9 (78%) 15/23 (65%)	N/A	N/A
Manosa	25 mg	Oral sc	7 33	Retrospective	26		24/40 (60%) remission	N/A
Saibeni	20 mg	Oral/ sc/im	23	Retrospective	N/A	11/23 (47.8%)		N/A
Khan	14 mg 25 mg	Oral sc/im	68 23	Retrospective	60	25/68 (37%) 7/23 (30%)		N/A

MTX: Methotrexate; CD: Crohn’s disease; AE: Adverse events; SC: Subcutaneous; PO: Oral; AZA: Azathioprine.

Table 3 Evidence for maintenance of remission of ulcerative colitis with methotrexate

Study	Dose (mean)	Route	No. of pts	Study design	Follow-upperiod (mo)	MTX responsemaintained?	Controlresponse	Significantlyeffective?
Kozarek	> 7.5 mg	sc	5	Open label	24	3/5 (60%)	N/A	N/A
Oren	12.5 mg	oral	32	Placebo-controlled	9	5/14 (36%)	10/18 (56%)	No
Mate-Jimenez	15 mg	oral	12	6-MP control	18	1/7 (14%)	7/11 (64%)	No
Paoluzi	12.5 mg	im	10	Open label	24	6/8 (75%)	N/A	N/A
Manosa	25 mg	Oral/	7	Retrospective	24	35%		N/A
		sc	33

MTX: Methotrexate.