Inflammatory Bowel Disease (IBD) pharmacotherapy and the risk of serious infection: a systematic review and network meta-analysis

Wheat, Chelle L.; Ko, Cynthia W.; Clark-Snustad, Kindra; Grembowski, David; Thornton, Timothy A.; Devine, Beth

doi:10.1186/s12876-017-0602-0

Table 1 Characteristics of included studies

From: Inflammatory Bowel Disease (IBD) pharmacotherapy and the risk of serious infection: a systematic review and network meta-analysis

Author	Journal	Publication Year	Region of Origin	Number of Sites	Study Duration^a (wks)	Diagnosis	Treatment Groups	Number of Patients	Mean Age (yrs)	Female (%)
Ardizzone [8]	Dig Liver Dis	2003	Europe (Western)	1	24	CD	MTX (25 mg/week) + prednisone (40 mg/day)	27	37.0	51.9
Ardizzone [8]	Dig Liver Dis	2003	Europe (Western)	1	24	CD	AZA (2 mg/kg/day) + prednisone (40 mg/day)	27	31.0	44.0
Ardizzone [9]	Gut	2006	Europe (Western)	1	24	UC	AZA (2 mg/kg/day) + prednisone (40 mg/day)	36	43.0	44.0
Ardizzone [9]	Gut	2006	Europe (Western)	1	24	UC	5-ASA (3.2 g/day) + prednisone (40 mg/day)	36	45.0	47.0
Arora [10]	Hepatogastroenterol	1999	N America	1	52	CD	MTX (15 mg/week) + prednisone (variable)	15	37.3	20.0
Arora [10]	Hepatogastroenterol	1999	N America	1	52	CD	Placebo + prednisone (variable)	18	35.6	55.6
Bar-Meir [11]	Gastroenterology	1998	Middle East	14	8	CD	Budesonide (9 mg/day)	100	32.7	47.0
Bar-Meir [11]	Gastroenterology	1998	Middle East	14	8	CD	Prednisone (40 mg/day)	101	32.8	49.5
Bar-Meir [12]	Dis Colon Rectum	2003	Worldwide	38	8	UC	Budesonide foam (2 mg/day)	120	42.0	62.0
Bar-Meir [12]	Dis Colon Rectum	2003	Worldwide	38	8	UC	Hydrocortisone foam (100 mg/day)	128	42.0	52.0
Colombel [13]	Gastroenterology	2007	Worldwide	92	56	CD	Adalimumab (40 mg/week or 40 mg/eow)	517	NR	61.9
Colombel [13]	Gastroenterology	2007	Worldwide	92	56	CD	Placebo	261	NR	62.1
Colombel [5]	N Engl J Med	2010	Worldwide	92	50	CD	Infliximab (5 mg/kg)	169	35.0	50.3
							AZA (2.5 mg/kg/day)	170	35.0	47.1
							Infliximab + AZA	169	34.0	47.9
Cortot [14]	Gut	2001	Worldwide	24	22	CD	Budesonide (6 mg/day) + prednisone (variable)	59	35.0	52.5
Cortot [14]	Gut	2001	Worldwide	24	22	CD	Placebo + prednisone (variable)	58	32.0	65.6
D’Haens [15]	Lancet	2008	Europe (Western)	18	104	CD	Infliximab (5 mg/kg) + AZA (2–2.5 mg/kg/day) (or MTX)	67	30.0	66.2
D’Haens [15]	Lancet	2008	Europe (Western)	18	104	CD	Prednisone (32 mg/day) or budesonide (9 mg/day)	66	28.7	57.8
Ewe [16]	Gastroenterology	1993	Europe (Western)	1	16	CD	AZA (2.5 mg/kg/day) + prednisone (60 mg/day)	21	27.3	NR
Ewe [16]	Gastroenterology	1993	Europe (Western)	1	16	CD	Placebo + prednisone (60 mg/day)	21	29.3	NR
Feagan [17]	N Engl J Med	1995	N America	8	16	CD	MTX (25 mg/week) + prednisone (20 mg/day)	94	34.0	46.0
Feagan [17]	N Engl J Med	1995	N America	8	16	CD	Placebo + prednisone (20 mg/day)	47	36.0	45.0
Feagan [18]	N Engl J Med	2000	N America	7	40	CD	MTX (15 mg/week)	40	32.0	60.0
Feagan [18]	N Engl J Med	2000	N America	7	40	CD	Placebo	36	34.0	39.0
Feagan [19]	Gastroenterology	2014	Canada	15	50	CD	Infliximab (5 mg/kg) + MTX (25 mg/week) + prednisone (variable)	63	40.4	46.6
							Infliximab + placebo + prednisone (variable)	63	38.5	41.3
Hanauer [20]	Gastroenterology	2004	N America	5	104	CD	6MP (50 mg/day)	47	34.9	51.0
							5-ASA (3 g/day)	44	34.1	57.0
							Placebo	40	34.2	55.0
Hawthorne [21]	BMJ	1992	Europe (Western)	5	52	UC	AZA (variable)	40	50.0	62.5
Hawthorne [21]	BMJ	1992	Europe (Western)	5	52	UC	Placebo	39	40.5	33.3
Lemann [22]	Gastroenterology	2006	Europe (Western)	22	52	CD	Infliximab (5 mg/kg) + AZA/6MP (2-3 mg/kg/day or 1–1.5 mg/kg/day) + prednisone (variable)	57	26.5	52.6
Lemann [22]	Gastroenterology	2006	Europe (Western)	22	52	CD	AZA/6MP + prednisone	56	27.5	57.1
Mantzaris [23]	Am J Gastroenterol	2004	Europe (Western)	1	104	UC	AZA (2.2 mg/kg/day) + 5-ASA (0.5 g TID)	36	33.0	50.0
Mantzaris [23]	Am J Gastroenterol	2004	Europe (Western)	1	104	UC	AZA	34	35.0	52.9
Neurath [24]	Gut	1999	Europe (Western)	1	24	CD	AZA (2.5 mg/kg/day) + prednisone (50 mg/day)	35	NR	NR
Neurath [24]	Gut	1999	Europe (Western)	1	24	CD	MMF (15 mg/kg/day) + prednisone (50 mg/day)	35	NR	NR
Ochsenkun [25]	Gastroenterology	2003	Not reported	Not reported	13	UC	Infliximab (5 mg/kg)	6	NR	NR
Ochsenkun [25]	Gastroenterology	2003	Not reported	Not reported	13	UC	Prednisone (1.5 mg/kg/day)	7	NR	NR
Odonnell [26]	Gut	1992	Europe (Western)	1	6	UC	5-ASA enemas (2 g/day)	24	49.0	28.3
Odonnell [26]	Gut	1992	Europe (Western)	1	6	UC	Prednisone enemas (20 mg/day)	21	43.0	61.9
Oren [27]	Gastroenterology	1996	Middle East	12	36	UC	MTX (12.5 mg/day)	30	38.3	43.3
Oren [27]	Gastroenterology	1996	Middle East	12	36	UC	Placebo	37	38.9	51.4
Orth [28]	Am J Gastroenterol	2000	Europe (Western)	1	52	UC	MMF (20 mg/kg/day) + prednisone (50 mg/day)	12	42.4	50.0
Orth [28]	Am J Gastroenterol	2000	Europe (Western)	1	52	UC	AZA (2 mg/kg/day) + prednisone (50 mg/day)	12	40.4	25.0
Prantera [29]	Gastroenterology	2012	Worldwide	55	12	CD	Rifaximin (400 mg/800 mg/1200 mg BID)	308	33.3	56.8
Prantera [29]	Gastroenterology	2012	Worldwide	55	12	CD	Placebo	102	37.0	59.0
Present [30]	N Engl J Med	1999	Worldwide	12	34	CD	Infliximab (5 mg/kg or 10 mg/kg)	63	38.1	57.1
Present [30]	N Engl J Med	1999	Worldwide	12	34	CD	Placebo	31	35.4	46.0
Rutgeerts [31]	Gastroenterology	1995	Europe (Western)	1	12	CD	Metronidazole (20 mg/kg/day)	30	33.0	NR
Rutgeerts [31]	Gastroenterology	1995	Europe (Western)	1	12	CD	Placebo	30	37.0	NR
Rutgeerts [32]	N Engl J Med	2005	Worldwide	62	46	UC	Infliximab (5 mg/kg or 10 mg/kg)	243	42.1	38.3
				62	46	UC	Placebo	121	41.4	40.5
				55	22	UC	Infliximab (5 mg/kg or 10 mg/kg)	241	40.4	40.2
				55	22	UC	Placebo	123	39.3	42.3
Rutgeerts [33]	Gastroenterology	2005	Europe (Western)	2	54	CD	Ornidazole (1 g/day)	38	35.0	57.9
Rutgeerts [33]	Gastroenterology	2005	Europe (Western)	2	54	CD	Placebo	40	30.5	50.0
Sandborn [34]	Gastroenterology	2003	N America	18	10	CD	Tacrolimus (0.2 mg/kg/day)	21	40.8	52.4
Sandborn [34]	Gastroenterology	2003	N America	18	10	CD	Placebo	25	38.1	66.0
Sandborn [35]	N Engl J Med	2005	Worldwide	142	12	CD	Natalizumab (300 mg)	724	38.0	57.0
					12	CD	Placebo	181	39.0	60.0
					48	CD	Natalizumab (300 mg)	168	37.0	54.0
					48	CD	Placebo	171	37.0	65.0
Sandborn [36]	Gut	2007	Worldwide	53	56	CD	Adalimumab (variable)	37	36.0	56.8
Sandborn [36]	Gut	2007	Worldwide	53	56	CD	Placebo	18	36.0	67.0
Sandborn [37]	N Engl J Med	2007	Worldwide	171	26	CD	Certolizumab pegol (400 mg)	331	37.0	53.0
Sandborn [37]	N Engl J Med	2007	Worldwide	171	26	CD	Placebo	329	38.0	60.0
Sandborn [38]	Gastroenterology	2012	Worldwide	103	52	UC	Adalimumab (variable)	248	39.6	42.7
Sandborn [38]	Gastroenterology	2012	Worldwide	103	52	UC	Placebo	246	41.3	38.2
Sandborn [39]	N Engl J Med	2012	Worldwide	153	36	CD	Ustekinumab (variable)	394	38.8	61.2
Sandborn [39]	N Engl J Med	2012	Worldwide	153	36	CD	Placebo	132	39.5	51.5
Sandborn [40]	N Engl J Med	2013	Worldwide	285	52	CD	Vedolizumab (300 mg)	967	35.7	53.4
Sandborn [40]	N Engl J Med	2013	Worldwide	285	52	CD	Placebo	148	38.6	53.4
Sandborn [41]	Gastroenterology	2014	Worldwide	251	52	UC	Golimumab (50 or 100 mg)	308	40.3	46.1
Sandborn [41]	Gastroenterology	2014	Worldwide	251	52	UC	Placebo	156	40.2	51.9
Sands [42]	Inflamm Bowel Dis	2007	N America	17	32	CD	Natalizumab (300 mg) + infliximab (5 mg/kg)	52	39.9	54.0
Sands [42]	Inflamm Bowel Dis	2007	N America	17	32	CD	Placebo + infliximab	27	38.9	37.0
Schreiber [43]	Gastroenterology	2005	Worldwide	58	20	CD	Certolizumab pegol (variable)	219	36.5	48.6
Schreiber [43]	Gastroenterology	2005	Worldwide	58	20	CD	Placebo	73	35.8	67.1
Schreiber [44]	N Engl J Med	2007	Worldwide	147	20	CD	Certolizumab pegol (400 mg)	215	38.0	57.0
Schreiber [44]	N Engl J Med	2007	Worldwide	147	20	CD	Placebo	210	38.0	48.0
Targan [45]	Gastroenterology	2007	Worldwide	114	8	CD	Natalizumab (300 mg)	259	38.1	59.0
Targan [45]	Gastroenterology	2007	Worldwide	114	8	CD	Placebo	250	37.7	59.0
Author	Journal	Mean Disease Duration (months)	Surgery (%)	Smoking History (%)	Concomitant Immunomodulator^b Use (%)	Concomitant 5-aminosalicylate Use (%)	Concomitant Steroid Use (%)	Observed Number of Serious Infections	Percentage of Serious Infections (%)	Bias Rating
Ardizzone [8]	Dig Liver Dis	76.6	33.0	NR	0.0	0.0	0.0	0	0.0	Low
Ardizzone [8]	Dig Liver Dis	57.3	30.0	NR	0.0	0.0	0.0	0	0.0	Low
Ardizzone [9]	Gut	64.4	NR	25.0	0.0	0.0	0.0	0	0.0	Low
Ardizzone [9]	Gut	67.5	NR	17.0	0.0	0.0	0.0	1	2.8	Low
Arora [1]	Hepatogastroenterol	109.2	26.7	NR	0.0	NR	0.0	1	6.7	Low
Arora [1]	Hepatogastroenterol	140.4	55.6	NR	0.0	NR	0.0	0	0.0	Low
Bar-Meir [11]	Gastroenterology	60.0	15.0	30.0	0.0	0.0	0.0	0	0.0	Low
Bar-Meir [11]	Gastroenterology	60.0	23.8	31.0	0.0	0.0	0.0	0	0.0	Low
Bar-Meir [12]	Dis Colon Rectum	42.0	NR	41.0	0.0	52.0	0.0	0	0.0	Low
Bar-Meir [12]	Dis Colon Rectum	45.6	NR	30.0	0.0	63.0	0.0	0	0.0	Low
Colombel [13]	Gastroenterology	NR	NR	35.6	51.0	39.3	38.9	14	2.7	Low
Colombel [13]	Gastroenterology	NR	NR	35.6	50.6	39.5	38.7	9	3.4	Low
Colombel [5]	N Engl J Med	26.4	NR	NR	0.0	51.5	47.4	8	4.7	Low
		28.8	NR	NR	0.0	61.2	38.2	9	5.3
		26.4	NR	NR	0.0	50.3	39.0	7	4.1
Cortot [14]	Gut	106.8	30.5	NR	15.3	49.2	0.0	0	0.0	Low
Cortot [14]	Gut	97.2	36.2	NR	8.6	48.3	0.0	0	0.0	Low
D’Haens [15]	Lancet	2.0	NR	55.4	0.0	4.6	0.0	4	6.0	Low
D’Haens [15]	Lancet	2.5	NR	60.9	0.0	3.1	0.0	7	10.6	Low
Ewe [16]	Gastroenterology	55.2	NR	NR	0.0	57.0	0.0	0	0.0	Low
Ewe [16]	Gastroenterology	46.8	NR	NR	0.0	37.0	0.0	0	0.0	Low
Feagan [17]	N Engl J Med	93.0	47.0	49.0	0.0	0.0	0.0	0	0.0	Low
Feagan [17]	N Engl J Med	98.0	47.0	47.0	0.0	0.0	0.0	0	0.0	Low
Feagan [18]	N Engl J Med	88.0	43.0	50.0	0.0	0.0	0.0	0	0.0	Low
Feagan [18]	N Engl J Med	84.0	36.0	42.0	0.0	0.0	0.0	1	2.8	Low
Feagan [19]	Gastroenterology	130.9	57.1	63.5	0.0	0.0	0.0	0	0.0	Low
Feagan [19]	Gastroenterology	115.4	46.0	57.2	0.0	0.0	0.0	0	0.0	Low
Hanauer [20]	Gastroenterology	113.0	100.0	NR	0.0	0.0	0.0	0	0.0	Low
		120.0	100.0	NR	0.0	0.0	0.0	0	0.0
		127.0	100.0	NR	0.0	0.0	0.0	0	0.0
Hawthorne [21]	BMJ	NR	NR	NR	0.0	80.0	NR	0	0.0	Low
Hawthorne [21]	BMJ	NR	NR	NR	0.0	85.0	NR	0	0.0	Low
Lemann [22]	Gastroenterology	48.0	NR	NR	0.0	0.0	0.0	0	0.0	Low
Lemann [22]	Gastroenterology	66.0	NR	NR	0.0	0.0	0.0	3	5.4	Low
Mantzaris [23]	Am J Gastroenterol	60.0	NR	8.0	0.0	0.0	0.0	0	0.0	Low
Mantzaris [23]	Am J Gastroenterol	48.0	NR	6.0	0.0	0.0	0.0	0	0.0	Low
Neurath [24]	Gut	NR	NR	NR	0.0	NR	0.0	0	0.0	Low
Neurath [24]	Gut	NR	NR	NR	0.0	NR	0.0	0	0.0	Low
Ochsenkun [25]	Gastroenterology	NR	NR	NR	NR	NR	NR	0	0.0	Uncertain
Ochsenkun [25]	Gastroenterology	NR	NR	NR	NR	NR	NR	0	0.0	Uncertain
Odonnell [26]	Gut	NR	NR	NR	NR	75.0	NR	0	0.0	Low
Odonnell [26]	Gut	NR	NR	NR	NR	71.4	NR	0	0.0	Low
Oren [27]	Gastroenterology	95.2	NR	51.7	0.0	66.7	70.0	0	0.0	Low
Oren [27]	Gastroenterology	70.2	NR	51.4	0.0	67.6	73.0	0	0.0	Low
Orth [28]	Am J Gastroenterol	149.0	0.0	NR	0.0	66.7	0.0	2	16.7	Low
Orth [28]	Am J Gastroenterol	87.0	0.0	NR	0.0	66.7	0.0	1	8.3	Low
Prantera [29]	Gastroenterology	40.0	28.6	21.8	25.2	67.4	48.8	1	0.3	Low
Prantera [29]	Gastroenterology	39.0	32.0	26.0	27.0	71.0	48.0	0	0.0	Low
Present [30]	N Engl J Med	151.2	60.3	NR	46.0	52.4	34.9	3	4.8	Low
Present [30]	N Engl J Med	144.0	59.0	NR	29.0	61.0	35.0	0	0.0	Low
Rutgeerts [31]	Gastroenterology	108.0	NR	NR	0.0	0.0	NR	0	0.0	Low
Rutgeerts [31]	Gastroenterology	120.0	NR	NR	0.0	0.0	NR	0	0.0	Low
Rutgeerts [32]	N Engl J Med	85.8	NR	46.1	51.4	69.1	58.8	11	4.5	Low
		74.4	NR	50.4	43.8	70.2	65.3	5	4.1
		79.2	NR	46.9	42.3	75.9	52.3	5	2.1
		78.0	NR	48.8	43.9	72.4	48.8	1	0.8
Rutgeerts [33]	Gastroenterology	84.0	100.0	44.7	0.0	0.0	52.3	0	0.0	Low
Rutgeerts [33]	Gastroenterology	36.0	100.0	47.5	0.0	0.0	35.0	0	0.0	Low
Sandborn [34]	Gastroenterology	NR	62.0	33.0	62.0	43.0	24.0	0	0.0	Low
Sandborn [34]	Gastroenterology	NR	44.0	16.0	14.0	40.0	16.0	0	0.0	Low
Sandborn [35]	N Engl J Med	121.0	41.0	23.0	34.0	47.0	38.0	12	1.7	Low
		110.0	40.0	24.0	28.0	44.0	40.0	4	2.2
		119.0	33.0	16.0	37.0	9.0	38.0	6	3.6
		116.0	40.0	26.0	35.0	54.0	46.0	5	2.9
Sandborn [36]	Gut	101.2	NR	86.5	24.3	70.3	45.9	0	0.0	Low
Sandborn [36]	Gut	98.9	NR	67.0	18.0	44.0	56.0	0	0.0	Low
Sandborn [37]	N Engl J Med	84.0	36.0	31.0	21.0	NR	22.0	7	2.1	Low
Sandborn [37]	N Engl J Med	96.0	34.0	33.0	20.0	NR	23.0	3	0.9	Low
Sandborn [38]	Gastroenterology	97.2	NR	NR	37.5	58.9	60.5	4	1.6	Low
Sandborn [38]	Gastroenterology	102.0	NR	NR	32.5	63.0	56.9	5	2.0	Low
Sandborn [39]	N Engl J Med	147.6	NR	NR	24.4	17.0	48.0	10	2.5	Low
Sandborn [39]	N Engl J Med	148.8	NR	NR	22.7	18.2	55.3	8	6.1	Low
Sandborn [40]	N Engl J Med	110.4	42.6	27.3	16.1	NR	34.7	45	4.7	Low
Sandborn [40]	N Engl J Med	98.4	36.5	23.0	16.9	NR	30.4	9	6.1	Low
Sandborn [41]	Gastroenterology	84.0	NR	NR	30.8	80.2	53.8	10	3.2	Low
Sandborn [41]	Gastroenterology	82.8	NR	NR	33.3	80.1	56.4	3	1.9	Low
Sands [42]	Inflamm Bowel Dis	150.3	NR	NR	50.0	46.0	27.0	0	0.0	Low
Sands [42]	Inflamm Bowel Dis	120.0	NR	NR	56.0	37.0	30.0	0	0.0	Low
Schreiber [43]	Gastroenterology	99.6	36.1	NR	37.4	44.3	34.7	1	0.4	Low
Schreiber [43]	Gastroenterology	95.4	37.0	NR	35.6	39.7	39.7	0	0.0	Low
Schreiber [44]	N Engl J Med	108.0	30.0	30.0	27.0	NR	22.0	6	2.8	Low
Schreiber [44]	N Engl J Med	84.0	35.0	36.0	25.0	NR	21.0	2	0.9	Low
Targan [45]	Gastroenterology	121.4	NR	NR	37.0	49.0	42.0	1	0.4	Low
Targan [45]	Gastroenterology	120.3	NR	NR	38.0	48.0	38.0	4	1.6	Low

Abbreviations: CD Crohn’s Disease, UC ulcerative colitis, NR not reported, MTX methotrexate, AZA azathioprine, 6MP 6-mercaptopurine, MMF mycophenolate mofetil
^ainclusive of active treatment period and follow-up
^bincludes MTX, 6MP, AZA
&Step-up paradigm starting with prednisone then progressing to AZA

Back to article page

ISSN: 1471-230X

Contact us

Submission enquiries: bmcgastroenterology@biomedcentral.com
General enquiries: ORSupport@springernature.com

BMC Gastroenterology

Contact us