Volume 126, Issue 4, Pages 989-996 (April 2004) A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn’s disease  Hiroaki Ito, Masakazu Takazoe, Yoshihiro Fukuda, Toshifumi Hibi, Kazuo Kusugami, Akira Andoh, Takayuki Matsumoto, Takehira Yamamura, Junichi Azuma, Norihiro Nishimoto, Kazuyuki Yoshizaki, Takashi Shimoyama, Tadamitsu Kishimoto  Gastroenterology  Volume 126, Issue 4, Pages 989-996 (April 2004) DOI: 10.1053/j.gastro.2004.01.012

Figure 1 Trial profile of patients with active Crohn’s disease who received MRA or placebo by masked randomization. aPlacebo biweekly; bMRA 8 mg/kg/placebo alternately, biweekly; cMRA 8 mg/kg biweekly; dsome patients had more than 1 reason, eanti-MRA mAb at baseline was subsequently determined to be a false positive. Gastroenterology 2004 126, 989-996DOI: (10.1053/j.gastro.2004.01.012)

Figure 2 Percentages of patients with Crohn’s disease with response (decrease in CDAI score from baseline ≥70 points) according to each treatment group. All significant differences are indicated in the Figure (χ2 test vs. placebo). M2W: MRA 8 mg/kg biweekly; M4W: MRA 8 mg/kg/placebo alternately, biweekly; Placebo: biweekly. Gastroenterology 2004 126, 989-996DOI: (10.1053/j.gastro.2004.01.012)

Figure 3 Median IBDQ scores according to each treatment group. M2W: MRA 8 mg/kg biweekly; M4W: MRA 8 mg/kg/placebo alternately, biweekly; Placebo: biweekly. ∗P < 0.05: significantly different from baseline based on paired t test. Gastroenterology 2004 126, 989-996DOI: (10.1053/j.gastro.2004.01.012)

Figure 4 Mean values for (A ) ESR, (B) CRP, (C ) SAA, and (D) fibrinogen concentrations after repeated administration according to each treatment group. ○: Placebo biweekly; ●: MRA 8 mg/kg/placebo alternately, biweekly; ■: MRA 8 mg/kg biweekly. ∗P < 0.05: significantly different from placebo based on Student t test. Bars indicate SD. Gastroenterology 2004 126, 989-996DOI: (10.1053/j.gastro.2004.01.012)

Figure 5 MRA induced apoptosis. Pairs of colonic tissue samples taken from an M2W patient before (A ) and after treatment (B) and from a placebo patient before (C ) and after treatment (D) were stained by using fluorescent TUNEL assay kit (MBL Co., Ltd., Nagoya, Japan; original magnification 100×). Gastroenterology 2004 126, 989-996DOI: (10.1053/j.gastro.2004.01.012)

Figure 6 Mean serum MRA concentration (mg/mL) after repeated administration. Serum samples were collected before each infusion and 1 hour after each infusion and at week 12. (A ) MRA 8 mg/kg were infused biweekly. (B) MRA 8 mg/kg or placebo were infused alternately, biweekly. The concentrations were under the limit of detection before each infusion at week 4, 8, and at week 12. Bars indicate SD. Gastroenterology 2004 126, 989-996DOI: (10.1053/j.gastro.2004.01.012)

Figure 7 Mean values for (A ) concentration of IL-6 and (B) concentration of sIL-6R after repeated administration according to each treatment group. ○: Placebo biweekly, ●: MRA 8 mg/kg/placebo alternately, biweekly; ■: MRA 8 mg/kg biweekly. Bars indicate SD. Gastroenterology 2004 126, 989-996DOI: (10.1053/j.gastro.2004.01.012)