Results: Over a 6– month period beginning in December of 2001, 43patients received a total of 75 infusions in our office–based infusion suite.All patients had a diagnosis of Crohn’s Disease (CD). Median patient agewas 14.7 years (range 8 yrs – 22 yrs). The usual dose was approximately5 mg/ kg body weight, with the total dose received rounded up to thenearest 100 mg increment. AntiTNF doses ranged from 4.3 mg/kg to 8.6mg/kg body weight, with infusions delivered over a 2 hour period using anescalating rate. All patients were pre–medicated with Benadryl; 30 werealso pre–medicated with acetominophen. Six patients received prednisoneor solumedrol. Nine of the 43 patients received their initial treatment in ourinfusion center, whereas the remaining 34 received previous infusions in ahospital or oncology infusion center. Seven patients received 3 consecutiveinfusions in our office. All 75 infusions were successfully completed with1 acute infusion reaction (1.3%). The patient experienced nausea, chestpain, and facial flushing 20 minutes after starting treatment. The infusionwas stopped, the patient was given 40 mg of solumedrol and 20 minuteslater the infusion was re–started at a slower rate. Parents and patientssubjectively reported their satisfaction with office based infusion, citing thefollowing: 1) comfort in having the access to physicians, nurses and officestaff familiar with the patients, 2) the ease of combining physician visitswith infusion appointments, and 3) the relaxed milieu of a pediatric office.Conclusions: This is the first report to describe the safety and patientsubjective satisfaction of a pediatric office based intravenous infusionprogram of AntiTNF therapy. Rigorous evaluation of AntiTNF therapy forpediatric patients with inflammatory bowel disease is still needed to de-termine its long–term safety and efficacy.

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MAINTENANCE THERAPY WITH INFLIXIMAB IN THEMANAGEMENT OF FISTULOUS CROHN’S DISEASENabeel Khan, M.D., Taylor Huynh–Le, Pharm.D. and Luis A. Balart,M.D.*. Section of Gastroenterology, Louisiana State University, NewOrleans, LA and Centocor Inc., Malvern, PA.

Purpose: Enterocutaneous fistulas are one of the most difficult to treat andserious manifestations of Crohn’s disease. The aim of this study was todetermine the efficacy of maintenance therapy with infliximab in thetreatment of fistulous disease.Methods: A retrospective chart review was performed on our patientstreated with infliximab over an eighteen–month period. Five of thesepatients were on maintenance therapy with infliximab for enterocutaneousfistulae. The patient’s age ranged from 42–55; 4 were female, 1 was male;and duration of illness ranged from 2–13 years. Previous medications,concurrent medications, and side effects were reviewed and an interviewwas conducted with each patient.Results: All of the patients had previously failed therapy including me-salamine (4), flagyl (4), imuran (2) and prednisone (2). All patients initiallyreceived a series of three infusions 5mg/kg at 0, 2 and 6 weeks and thenmaintenance therapy every 8 weeks at the same dosage. The duration oftreatment ranged from 10–26 months. All the patients were concurrentlytaking imuran. Four of the five patients became completely asymptomaticwith no drainage from the fistulas. The fifth patient noted marked improve-ment but not complete resolution of her symptoms. There were no seriousadverse events.Conclusions: Maintenance therapy with infliximab is safe and highlyeffective in the management of difficult to treat fistulous Crohn’s disease.

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MAINTENANCE INFLIXIMAB IS SAFE AND EFFECTIVE INFISTULIZING CROHN’S DISEASE(CD); RESULTS FROM THEACCENT II TRIALBruce Sands*, Sander Van Deventer, Marion Blank, Paul Marsters,Suzanne Travers and Accent II Trial. Massachusetts General Hospital,Boston, MA; Afdeling Gastro–enterologie Academic Medical Center,Amsterdam, Netherlands and Centocor, Inc., Malvern, PA.

Purpose: The ACCENT II trial determined the efficacy and safety ofmaintenance dosing with infliximab (IFX) in reducing the number ofdraining enterocutaneous fistulas compared to a 3–dose induction regimenof IFX only.Methods: Patients (pts) received 5 mg/kg IFX at weeks (wks) 0, 2 and 6.Fistula response was defined as �50% reduction from baseline in thenumber of draining fistulas at both wks 10 and 14. Pts with a fistularesponse were randomized at wk 14 to receive subsequent placebo or IFX5 mg/kg infusions every 8 wks through week 46. The primary efficacyendpoint was defined as time to loss of fistula response (defined as a �50%reduction from baseline in the number of draining fistulas, confirmed overa period of at least 4 wks or by other medical/surgical intervention) throughwk 54.Results: 306 pts were enrolled. 195 of 282 (69%) pts present at wk 14achieved fistula response. The time to loss of response was longer for ptsreceiving IFX maint. than for pts receiving placebo maint. (p�0.001). Themedian time to loss of response was 14 wks following randomization (atwk 14) for placebo maint., and �40 wks for IFX maint. 42% of IFX maint.pts had fistula response at all 5 visits from wk 22 to wk 54 vs. 21% onplacebo maint. At wk 30, 48% on IFX maint. had complete fistula response(no draining fistulas) vs. 27% on placebo maint. (p�0.002). At wk 54, 36%(IFX maint.) vs. 19% (placebo maint.) were in complete response(p�0.009). Median duration of fistula closure was 40 weeks (IFX maint.)vs. 23 wks (placebo maint.). Greater improvement in CDAI and IBDQ wasobserved for IFX compared to placebo maint. at wks 30 and 54 (p�0.05).Through approx. 51 wks of follow–up, serious infections occurred in 5%and infections requiring treatment occurred in 30% of all 282 pts andinfusion reactions occurred in 4% of IFX infusions, results consistent withcurrent labeling. No malignancies were reported.Conclusions: In pts with fistulizing CD, maintenance treatment with 5mg/kg IFX was more effective than a 3–dose induction regimen. IFXmaintenance was well–tolerated in pts treated for up to 46 wks.

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INFLIXIMAB DOWNREGULATES GELATINASE B ANDTENASCIN IN THE MUCOSA OF CROHN’S DISEASEPATIENTSKarel Geboes, M.D., Ph.D.*, Paul Rutgeerts, D. Ph.D., Carrie Wagner,Ph.D., Allan Olson, M.D., Freddy Cornillie, Ph.D., Weihang Bao, Ph.D.and Colleen Marano, Ph.D. Department of Pathology, UZ St. Rafael,Leuven, Belgium; Department of Gastroenterology, University HospitalGasthuisberg, Herestraat 49, Leuven, Belgium and Centocor, Inc,Malvern, PA.

Purpose: In ACCENT I, infliximab was assessed for its effect on theexpression of the matrix metalloproteinase, gelatinase B, and the extracel-lular matrix protein, tenascin, in mucosal biopsies collected as part of ahistological substudy.Methods: 573 Crohn’s disease patients with a CDAI between 220 and 400received a single infusion of 5mg/kg infliximab. At week (wk) 2, respond-ers (�70 point decrease in CDAI and �25% decrease from baseline) andnon–responders were randomized to 1 of 3 maintenance regimens: 1)placebo at wks 2, 6 and then placebo q 8 weeks, 2) 5 mg/kg infliximab atwks 2, 6 and then 5 mg/kg infliximab q 8 weeks, and 3) 5 mg/kg infliximabat wks 2, 6 and then 10 mg/kg infliximab q 8 wks. Patients who lost clinicalresponse were eligible go on episodic retreatment at wk 14 at a dose ofinfliximab 5mg/kg greater than their maintenance dose. Mucosal biopsieswere collected at wks 0, 10 and 54 from a subset of all patients randomizedto each treatment group at wk 2. Immunohistochemical methods were usedto detect gelatinase B–positive mononuclear cells as well as the expressionof tenascin in the subepithelium and lamina propria.Results: The expression of gelatinase B–positive mononuclear cells wasmarkedly decreased at wk 10 after a single dose or a 3–dose inductionregimen of infliximab. Subepithelial and lamina propria expression oftenascin was also decreased at wk 10 with the effect of infliximab beinggreater in the three–dose treatment group compared to the single dosegroup. After the 3–dose induction at wks 0, 2 and 6, continued maintenance

S258 Abstracts AJG – Vol. 97, No. 9, Suppl., 2002