Targan et al.55. Targan SR, Hanauer SB, Deventer SJV, Mayer L, Present DH, Braakman T, et al. A Short-Term Study of Chimeric Monoclonal Antibody cA2 to Tumor Necrosis Factor α for Crohns Disease. N Engl J Med. 1997;337:1029-36. (1997) |
Multicenter, double-blind, placebo-controlled RCT. n=108 |
Patients with moderate to severe CD refractory to 5-ASA and steroids. |
Reduction of CDAI ≥70 points after 4 weeks of single induction dose. |
12 weeks |
|
Clinical response (week 4) |
|
|
|
|
|
Placebo (n=25) |
17% |
|
|
|
|
|
IFX 5 mg/kg (n=27) |
81% |
|
|
|
|
|
IFX 10 mg/kg (n=28) |
50% |
|
|
|
|
|
IFX 20 mg/kg (n=28) |
64% |
|
|
|
|
|
|
|
CLASSIC I66. Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, Macintosh D, et al. Human Anti-Tumor Necrosis Factor Monoclonal Antibody (Adalimumab) in Crohn’s Disease: the CLASSIC-I Trial. Gastroenterology. 2006;130:323-33. (2006) |
Multicenter, double-blind, placebo-controlled RCT. n=299 |
Patients with moderate to severe CD naive to anti-TNF therapy. |
Clinical remission (CDAI <150) at week 4 after initial induction therapy. |
4 weeks |
|
Clinical remission (week 4) |
|
|
|
|
|
Placebo (n=74) |
12% |
|
|
|
|
|
ADA 40 mg/ 20 mg (n=74) |
18% |
|
|
|
|
|
ADA 80 mg/ 40 mg (n=75) |
24% |
|
|
|
|
|
ADA 160 mg/ 80 mg (n=76) |
36% |
|
|
|
|
|
|
|
ACCENT I77. Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Maintenance infliximab for Crohns disease: the ACCENT I randomised trial. The Lancet. 2002;359:1541-9. (2002) |
Multicenter, double-blind, randomized controlled RCT. n=335 |
Patients with luminal CD that responded to a single infusion of IFX within 2 weeks. |
Clinical remission (defined as a CDAI score <150) at week 30. |
54 weeks |
|
Clinical remission (week 30) |
|
|
|
|
|
Placebo (n=110) |
21% |
|
|
|
|
|
IFX 5 mg/kg (n=113) |
39% |
|
|
|
|
|
IFX 10 mg/kg (n=112) |
45% |
|
|
|
|
|
|
|
Schnitzler et al.88. Schnitzler F, Fidder H, Ferrante M, Noman M, Arijs I, Assche GV, et al. Long-term outcome of treatment with infliximab in 614 patients with Crohns disease: results from a single-centre cohort. Gut. 2008;58:492-500. (2009) |
Single centre, real-life cohort. n=614 |
CD patients (treated for luminal, perianal or extraintestinal manifestations). |
Assess the patients with initial response to IFX who had sustained clinical benefit at the end of follow-up. |
55 months |
|
Clinical response (week 10) |
|
|
|
|
|
IFX 5 mg/kg - single dose (n=432) |
87.7% |
|
|
|
|
|
IFX 5 mg/kg 0, 2 and 6 (n=182) |
92.3% |
|
|
|
|
|
|
|
Present et al.1010. Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, Hogezand RV, et al. Infliximab for the Treatment of Fistulas in Patients with Crohns Disease. N Engl J Med . 1999;340:1398-405. (1999) |
Randomized, multicenter, double-blind, placebo-controlled RCT. n=94 |
Patients who had draining abdominal or perianal fistulas of at least three months’ duration. |
Reduction of ≥50% from base line in the number of draining fistulas. |
18 weeks |
|
Achieved primary endpoint |
|
|
|
|
|
Placebo (n=31) |
26% |
|
|
|
|
|
IFX 5 mg/kg (n=31) |
68% |
|
|
|
|
|
IFX 10 mg/kg (n=32) |
56% |
|
|
|
|
|
|
|
ACCENT II1111. Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, et al. Infliximab Maintenance Therapy for Fistulizing Crohns Disease. N Engl J Med . 2004;350:876-85. (2004) |
Multicenter, double-blind, randomized, placebo-controlled. n=306 |
Patients with CD and one or more fistulas, with active drainage, abdominal or perianal, of at least three months duration. |
Time to loss of response during follow-up among patients who had a response at week 14 and were randomized. |
54 weeks |
|
Absence of draining fistulas (week 54) |
|
|
|
|
|
Placebo |
19% |
|
|
|
|
|
IFX 5 mg/kg |
36% |
|
|
|
|
|
|
Median time to loss of response |
|
|
|
|
|
Placebo |
14 weeks |
|
|
|
|
|
IFX 5 mg/kg |
>40 weeks |
|
|
|
|
|
|
|
CHARM1212. Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, et al. Adalimumab for Maintenance of Clinical Response and Remission in Patients With Crohn’s Disease: The CHARM Trial. Gastroenterology. 2007;132:52-65. (2007) |
Multicenter, randomized, double-blind, placebo-controlled. n=854 |
Patients with moderate to severe luminal and fistulizing CD for at least 4 months. |
Percentage of randomized responders who achieved clinical remission (CDAI <150) at weeks 26 and 56. |
56 weeks |
|
Clinical remission at week |
|
|
|
|
|
|
26 |
56 |
|
|
|
|
|
Placebo (n=170) |
17% |
12% |
|
|
|
|
|
ADA 40mg w (n=157) |
47% |
41% |
|
|
|
|
|
ADA 40mg eow (n=172) |
40% |
36% |
|
|
|
|
|
|
Complete fistula closure at week |
|
|
|
|
|
|
26 |
56 |
|
|
|
|
|
Placebo (n=47) |
13% |
13% |
|
|
|
|
|
ADA-treated patients (n=70) |
30% |
33% |
|
|
|
|
|
|
|
Regueiro et al.1313. Swoger JM, Regueiro M. Preventive therapy in postoperative Crohn’s disease. Current Opinion in Gastroenterology. 2010;26:337-43. (2009) |
Randomized, double-blind, placebo-controlled RCT. n=24 |
Patients with CD who had undergone ileocolonic resection and were allocated to receive intravenous IFX or placebo administered within 4 weeks of surgery and continued for 1 year. |
Proportion of patients with endoscopic recurrence at 1 year after surgery. |
1 year |
|
Endoscopic recurrence (1 year) |
|
|
|
|
|
Placebo (n=13) |
84.6% |
|
|
|
|
|
IFX 5 mg/kg (n=11) |
9.1% |
|
|
|
|
|
|
|
PREVENT1717. Regueiro M, Feagan BG, Zou B., Johanns J, Blank MA, Chevrier M, et al. Infliximab reduces endoscopic, but not clinical, recurrence of Crohn’s disease after ileocolonic resection. Gastroenterology. 2016;150(7). (2016) |
Multicenter, randomized, double-blind, placebo-controlled RCT. n=297 |
Patients with CD which had undergone ileocolonic resection within 45 days before randomization. |
Clinical recurrence prior to or at week 76 and evidence of endoscopic recurrence. |
76 weeks |
|
Endoscopic recurrence (≤76 weeks) |
|
|
|
|
|
Placebo (n=150) |
60.0% |
|
|
|
|
|
IFX 5 mg/kg (n=147) |
30.6% |
|
|
|
|
|
|
|
POCER1818. Cruz PD, Kamm MA, Hamilton AL, Ritchie KJ, Krejany EO, Gorelik A, et al. Crohns disease management after intestinal resection: a randomised trial. The Lancet . 2015;385:1406-17. (2015) |
Part of multicenter, randomized, double-blind, placebo-controlled RCT. n=101 |
Patients with CD undergoing intestinal resection of all macroscopic disease, with an endoscopically accessible anastomosis. |
Presence and severity of endoscopic recurrence 6 months after surgery. |
6 months |
Colonoscopy at 6 month post-operatively |
Endoscopic recurrence |
|
|
|
|
|
Thiopurine (n=62) |
39% |
|
|
|
|
|
ADA 160/80 (followed by 40 mg eow) (n=24) |
13% |
|
|
|
|
|
|
|
Savarino et al.1919. Savarino E, Bodini G, Dulbecco P, Assandri L, Bruzzone L, Mazza F, et al. Adalimumab Is More Effective Than Azathioprine and Mesalamine at Preventing Postoperative Recurrence of Crohn’s Disease: A Randomized Controlled Trial. Am J Gastroenterol. 2013;108:1731-42. (2013) |
Randomized, prospective, three-armed, unblended. n=51 |
Patients with ileal or ileocolonic CD undergoing resection to receive after 2 weeks from surgery ADA, AZA or Mesalamine. |
Proportion of patients with endoscopic and clinical recurrence at 2 years after surgery. |
2 years |
|
Endoscopic recurrence |
|
|
|
|
|
ADA 160/80 mg (followed by 40 mg eow) (n=16) |
6.3% |
|
|
|
|
|
AZA 2 mg/kg/day (n=17) |
64.7% |
|
|
|
|
|
Mesalamine 3g/day (n=18) |
83.3% |