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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 Durationa (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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Placebo 31 35.4 46.0
Rutgeerts [31] Gastroenterology 1995 Europe (Western) 1 12 CD Metronidazole (20 mg/kg/day) 30 33.0 NR
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
Placebo 121 41.4 40.5
55 22 UC Infliximab (5 mg/kg or 10 mg/kg) 241 40.4 40.2
Placebo 123 39.3 42.3
Rutgeerts [33] Gastroenterology 2005 Europe (Western) 2 54 CD Ornidazole (1 g/day) 38 35.0 57.9
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
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
Placebo 181 39.0 60.0
48 CD Natalizumab (300 mg) 168 37.0 54.0
Placebo 171 37.0 65.0
Sandborn [36] Gut 2007 Worldwide 53 56 CD Adalimumab (variable) 37 36.0 56.8
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
Placebo 329 38.0 60.0
Sandborn [38] Gastroenterology 2012 Worldwide 103 52 UC Adalimumab (variable) 248 39.6 42.7
Placebo 246 41.3 38.2
Sandborn [39] N Engl J Med 2012 Worldwide 153 36 CD Ustekinumab (variable) 394 38.8 61.2
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
Placebo 148 38.6 53.4
Sandborn [41] Gastroenterology 2014 Worldwide 251 52 UC Golimumab (50 or 100 mg) 308 40.3 46.1
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
Placebo + infliximab 27 38.9 37.0
Schreiber [43] Gastroenterology 2005 Worldwide 58 20 CD Certolizumab pegol (variable) 219 36.5 48.6
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
Placebo 210 38.0 48.0
Targan [45] Gastroenterology 2007 Worldwide 114 8 CD Natalizumab (300 mg) 259 38.1 59.0
Placebo 250 37.7 59.0
Author Journal Mean Disease Duration (months) Surgery (%) Smoking History (%) Concomitant Immunomodulatorb 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
57.3 30.0 NR 0.0 0.0 0.0 0 0.0
Ardizzone [9] Gut 64.4 NR 25.0 0.0 0.0 0.0 0 0.0 Low
67.5 NR 17.0 0.0 0.0 0.0 1 2.8
Arora [1] Hepatogastroenterol 109.2 26.7 NR 0.0 NR 0.0 1 6.7 Low
140.4 55.6 NR 0.0 NR 0.0 0 0.0
Bar-Meir [11] Gastroenterology 60.0 15.0 30.0 0.0 0.0 0.0 0 0.0 Low
60.0 23.8 31.0 0.0 0.0 0.0 0 0.0
Bar-Meir [12] Dis Colon Rectum 42.0 NR 41.0 0.0 52.0 0.0 0 0.0 Low
45.6 NR 30.0 0.0 63.0 0.0 0 0.0
Colombel [13] Gastroenterology NR NR 35.6 51.0 39.3 38.9 14 2.7 Low
NR NR 35.6 50.6 39.5 38.7 9 3.4
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
97.2 36.2 NR 8.6 48.3 0.0 0 0.0
D’Haens [15] Lancet 2.0 NR 55.4 0.0 4.6 0.0 4 6.0 Low
2.5 NR 60.9 0.0 3.1 0.0 7 10.6
Ewe [16] Gastroenterology 55.2 NR NR 0.0 57.0 0.0 0 0.0 Low
46.8 NR NR 0.0 37.0 0.0 0 0.0
Feagan [17] N Engl J Med 93.0 47.0 49.0 0.0 0.0 0.0 0 0.0 Low
98.0 47.0 47.0 0.0 0.0 0.0 0 0.0
Feagan [18] N Engl J Med 88.0 43.0 50.0 0.0 0.0 0.0 0 0.0 Low
84.0 36.0 42.0 0.0 0.0 0.0 1 2.8
Feagan [19] Gastroenterology 130.9 57.1 63.5 0.0 0.0 0.0 0 0.0 Low
115.4 46.0 57.2 0.0 0.0 0.0 0 0.0
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
NR NR NR 0.0 85.0 NR 0 0.0
Lemann [22] Gastroenterology 48.0 NR NR 0.0 0.0 0.0 0 0.0 Low
66.0 NR NR 0.0 0.0 0.0 3 5.4
Mantzaris [23] Am J Gastroenterol 60.0 NR 8.0 0.0 0.0 0.0 0 0.0 Low
48.0 NR 6.0 0.0 0.0 0.0 0 0.0
Neurath [24] Gut NR NR NR 0.0 NR 0.0 0 0.0 Low
NR NR NR 0.0 NR 0.0 0 0.0
Ochsenkun [25] Gastroenterology NR NR NR NR NR NR 0 0.0 Uncertain
NR NR NR NR NR NR 0 0.0
Odonnell [26] Gut NR NR NR NR 75.0 NR 0 0.0 Low
NR NR NR NR 71.4 NR 0 0.0
Oren [27] Gastroenterology 95.2 NR 51.7 0.0 66.7 70.0 0 0.0 Low
70.2 NR 51.4 0.0 67.6 73.0 0 0.0
Orth [28] Am J Gastroenterol 149.0 0.0 NR 0.0 66.7 0.0 2 16.7 Low
87.0 0.0 NR 0.0 66.7 0.0 1 8.3
Prantera [29] Gastroenterology 40.0 28.6 21.8 25.2 67.4 48.8 1 0.3 Low
39.0 32.0 26.0 27.0 71.0 48.0 0 0.0
Present [30] N Engl J Med 151.2 60.3 NR 46.0 52.4 34.9 3 4.8 Low
144.0 59.0 NR 29.0 61.0 35.0 0 0.0
Rutgeerts [31] Gastroenterology 108.0 NR NR 0.0 0.0 NR 0 0.0 Low
120.0 NR NR 0.0 0.0 NR 0 0.0
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
36.0 100.0 47.5 0.0 0.0 35.0 0 0.0
Sandborn [34] Gastroenterology NR 62.0 33.0 62.0 43.0 24.0 0 0.0 Low
NR 44.0 16.0 14.0 40.0 16.0 0 0.0
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
98.9 NR 67.0 18.0 44.0 56.0 0 0.0
Sandborn [37] N Engl J Med 84.0 36.0 31.0 21.0 NR 22.0 7 2.1 Low
96.0 34.0 33.0 20.0 NR 23.0 3 0.9
Sandborn [38] Gastroenterology 97.2 NR NR 37.5 58.9 60.5 4 1.6 Low
102.0 NR NR 32.5 63.0 56.9 5 2.0
Sandborn [39] N Engl J Med 147.6 NR NR 24.4 17.0 48.0 10 2.5 Low
148.8 NR NR 22.7 18.2 55.3 8 6.1
Sandborn [40] N Engl J Med 110.4 42.6 27.3 16.1 NR 34.7 45 4.7 Low
98.4 36.5 23.0 16.9 NR 30.4 9 6.1
Sandborn [41] Gastroenterology 84.0 NR NR 30.8 80.2 53.8 10 3.2 Low
82.8 NR NR 33.3 80.1 56.4 3 1.9
Sands [42] Inflamm Bowel Dis 150.3 NR NR 50.0 46.0 27.0 0 0.0 Low
120.0 NR NR 56.0 37.0 30.0 0 0.0
Schreiber [43] Gastroenterology 99.6 36.1 NR 37.4 44.3 34.7 1 0.4 Low
95.4 37.0 NR 35.6 39.7 39.7 0 0.0
Schreiber [44] N Engl J Med 108.0 30.0 30.0 27.0 NR 22.0 6 2.8 Low
84.0 35.0 36.0 25.0 NR 21.0 2 0.9
Targan [45] Gastroenterology 121.4 NR NR 37.0 49.0 42.0 1 0.4 Low
120.3 NR NR 38.0 48.0 38.0 4 1.6
  1. Abbreviations: CD Crohn’s Disease, UC ulcerative colitis, NR not reported, MTX methotrexate, AZA azathioprine, 6MP 6-mercaptopurine, MMF mycophenolate mofetil
  2. ainclusive of active treatment period and follow-up
  3. bincludes MTX, 6MP, AZA
  4. &Step-up paradigm starting with prednisone then progressing to AZA