Low-Dose Maintenance Therapy With Infliximab Prevents Postsurgical Recurrence of Crohn's Disease  Dario Sorrentino, Alberto Paviotti, Giovanni Terrosu, Claudio Avellini, Marco Geraci, Dimitra Zarifi  Clinical Gastroenterology and Hepatology  Volume 8, Issue 7, Pages 591-599.e1 (July 2010) DOI: 10.1016/j.cgh.2010.01.016 Copyright © 2010 AGA Institute Terms and Conditions

Figure 1 Design of the dose-finding study. The initial low dose of infliximab was 1 mg/kg bw. IFX, infliximab; MH, mucosal healing. Clinical Gastroenterology and Hepatology 2010 8, 591-599.e1DOI: (10.1016/j.cgh.2010.01.016) Copyright © 2010 AGA Institute Terms and Conditions

Figure 2 Postsurgery endoscopic score versus infliximab dose. The graph illustrates the endoscopic scores at each infliximab dose in the 10 patients presenting with postsurgical recurrence (score, ≥2) 16 weeks after stopping therapy. Individual data points are plotted as sunflowers with multiple petals. The boxes (dotted line) are centered on the mean (solid line) of the scores observed at different infliximab doses, with total height equal to twice the standard deviation. The statistical significance (P) for the median difference between pairs of endoscopic scores at different drug doses also is reported. IFX, infliximab; q8wk, 8-week dosing interval. Clinical Gastroenterology and Hepatology 2010 8, 591-599.e1DOI: (10.1016/j.cgh.2010.01.016) Copyright © 2010 AGA Institute Terms and Conditions

Figure 3 Appearance of the mucosal anastomosis at different infliximab doses: (A) 5 mg/kg bw on an 8-week dosing interval for 3 years after surgery; (B) 1 mg/kg bw, 4 weeks after 3 infusions on an 8-week dosing interval; (C) 2 mg/kg bw, 4 weeks after 3 infusions on an 8-week dosing interval; (D) 3 mg/kg bw, 4 weeks after 3 infusions on an 8-week dosing interval; and (E) 3 mg/kg bw on an 8-week dosing interval for 1 year. The progressive increase in infliximab dose re-established mucosal integrity, which was maintained at 1 year. Clinical Gastroenterology and Hepatology 2010 8, 591-599.e1DOI: (10.1016/j.cgh.2010.01.016) Copyright © 2010 AGA Institute Terms and Conditions

Figure 4 Markers of inflammation versus infliximab dose. Markers were measured before colonoscopy and after at least one additional infliximab infusion at any given dose (see Patients and Methods section). (A) FC decreased gradually with increasing doses of infliximab, approaching the normal range (broken line) at 3 mg/kg bw. (B) CRP clearly was increased in the majority of patients at the lowest infliximab dose (1 mg/kg bw), but it decreased to within the normal range (below the broken line) starting at 2 mg/kg bw. (C) There was no clear relationship evident between ESR and infliximab dose. Broken line, upper limit of the normal range. Clinical Gastroenterology and Hepatology 2010 8, 591-599.e1DOI: (10.1016/j.cgh.2010.01.016) Copyright © 2010 AGA Institute Terms and Conditions

Figure 5 FC versus endoscopic scores (Rutgeerts). As predicted by the correlation between infliximab dose and endoscopic score (Figures 2 and 3) and between FC and infliximab dose (Figure 4A), there was a close association in the 10 treated patients between FC and endoscopic scores (P < .0001). FC was measured 3 days before preparation for colonoscopy. Individual data points appear superimposed because of graph compression. FC (mg/kg) is expressed in natural logarithms. Solid line, estimated median regression line. Clinical Gastroenterology and Hepatology 2010 8, 591-599.e1DOI: (10.1016/j.cgh.2010.01.016) Copyright © 2010 AGA Institute Terms and Conditions

Supplementary Figure 1 Appearance of the mucosal anastomosis during infliximab treatment and after its suspension. (A) The patient had been treated for 3 years after surgery with infliximab 5 mg/kg bw. (B) The same patient 16 weeks after interruption of infliximab therapy. Clinical Gastroenterology and Hepatology 2010 8, 591-599.e1DOI: (10.1016/j.cgh.2010.01.016) Copyright © 2010 AGA Institute Terms and Conditions