1. MIGUEL REGUEIRO, WOLFGANG SCHRAUT, LEONARD BAIDOO, KEVIN E. KIP, ANTONIA R. SEPULVEDA, MARILYN PESCI, JANET HARRISON, SCOTT E. PLEVY GASTROENTEROLOGY 2009;136:441–450 R3 Yeon-Ju Kim 1 Infliximab Prevents Crohn’s Disease Recurrence After Ileal Resection

2. Background Crohn’s disease  commonly involves the terminal ileum and proximal colon  approximately 75% of CD pts require an intestinal resection  Histologic recurrence of CD :1 week after surgery  Endoscopic evidence of recurrent CD(70~90%) : 1 year after intestinal resection  Clinical recurrence : one third of pts 3 years after surgery and in 60% by 10yrs → Endoscopic recurrence correlates with the likelihood of future clinical recurrence, and predicts the development of CD related complications and need for re-operation → Endoscopic f/u evaluation 6–12 months after surgery 2

3. Background Infliximab in Crohn’s disease  Recurrent disease : Infliximab should be reserved for patients (1) steroids are contraindicated (2) remission is not achieved within four months of combined Tx  Fistulae: Infliximab is indicated if surgery,azathioprine, and/or antibiotic treatment are unsuccessful in fistulising disease. Postgrad. Med. J. 2001;77;436-440 Infliximab With Low-Dose Methotrexate for Prevention of Postsurgical Recurrence of Ileocolonic Crohn’s Disease → show that in the group treated postoperatively with infliximab(5mg/kg) and low-dose methotrexate(10mg/wk), none has had, after 2 years, endoscopic or clinical recurrence, whereas 75% of the pts treated with mesalamine(2.4g/day) alone had clinical or endoscopic recurrence. Arch Intern Med. 2007;167(16):1804-1807 3

4. Materials and Methods 2005~2007 : 24 patients : randomized, two-armed, double-blind, placebocontrolled trial  The Inflammatory Bowel Disease Center at the University of Pittsburgh Medical Center  within 4 weeks of resection (ileocolonic anastomosis)  infliximab 5mg/kg or placebo  at 0, 2, and 6 weeks, followed by every 8 weeks for 54 weeks Exclusion criteria (1) ≥10 years of Crohn’s disease requiring first resective surgery for short (10 cm) fibrostenotic stricture (2) macroscopically active disease not resected at the time of surgery (3) presence of a stoma (4) prior severe reactions to infliximab 4

5. Materials and Methods Study Outcomes  Primary end points : the proportion of pts with endoscopic recurrence at 1 year after surgery –Endoscopic recurrence : i2, i3, or i4 –Endoscopic remission : i0 or i1  Secondary end points : clinical recurrence and remission Histologic recurrence –Clinical recurrence : Crohn’s Disease Activity Index(CDAI) score ≥200 –Clinical remission : CDAI score ≤150 –Histologic recurrence : based on a histologic activity score and the presence of neutrophils * Endoscopic score i0 : no lesions i1 : < 5 aphthous lesions I 2 : ≥ 5 aphthous lesions with normal mucosa between the lesions or skip areas of larger lesions or lesions confined to the ileocolonic anastomosis i3 : diffuse aphthous ileitis with diffusely inflamed mucosa i4 : diffuse inflammation with large ulcers, nodules, and/or narrowing 5

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13. Conclusion Administration of infliximab after intestinal resective surgery was effective at preventing endoscopic and histologic recurrence of Crohn’s disease. 13

14. CDAI score Diagnostic test: clinical prediction rule- Crohn's disease activity index, based on symptoms over last week: –number of liquid or very soft stools: multiplication factor, 2 –abdominal pain (0 = none; 1 = mild; 2 = moderate, 3 =severe): 5 –general well-being (0 = generally well, 1 = slightly under par, 2 = poor, 3 = very poor, 4 = terrible): 7 –number of complaints patient now has: arthritis/ athralgia; iritis/ uveitis; erythema nodosum/ pyoderma gangrenosum/apthous stomatitis; anal fissure, fistula or abscess; other fistula; fever > 37.8 C in last week: 20 –taking loperamide/opiates for diarrhoea (0 = no, 1 = yes): 30 –abdominal mass (0 = none, 2 = questionable, 5 = definite): 10 –haematocrit: male (47- Hct); female (42- Hct): 6 –% below predicted body weight: 1 14