prescriptions before had an adjusted OR of 0.66 [0.15–2.85]; with 13 to 30prior prescriptions this was 0.36 [0.12–1.06] and with � 30 prior prescrip-tions this was 0.73 [0.35–1.50]. For mesalazine users, these figures were1.02 [0.44–2.35], 0.27 [0.10–0.76], and 0.31 [0.11–0.85], respectively.Conclusions: In conclusion, these results support earlier work suggestinga possible preventative effect of 5-ASA in the development of CRC inulcerative colitis.

738

SIMULTANEOUS ANTIBODY BLOCKADE OF L-SELECTINAND MADCAM-1 IS REQUIRED FOR AMELIORATION OFCHRONIC ILEITIS IN THE SAMP1/YIT FC-SCID ADOPTIVETRANSFER MODEL OF CROHN’S DISEASEJesus Rivera-Nieves, M.D., Fabio Cominelli, M.D., Ph.D.,Klaus Ley, M.D.*. University of Virginia, Charlottesville, VA.

Purpose: The effectiveness of biological therapies other than infliximab(e.g. IL-10, IL-11 blockade) for the treatment of Crohn’s disease (CD) hasbeen limited. We propose that simultaneous blockade of two or moregut-homing adhesion molecules and/or chemokines (i.e. L-selectin, �7integrin, MAdCAM-1 and CCR9) will be required, due to redundancies inthe lymphocyte adhesion cascade.Methods: Specific monoclonal antibodies against integrins �7, �4, �4�7dimer, L-selectin and MAdCAM-1 were injected alone or in combinationthrough the first week of SAMP1/ YitFc-SCID CD4� T cell adoptivetransfer (200 mg, Q.O.D., I.P 4) or 5 weeks after transfer (200 mg,Q.O.D., I.P. 3). Ileal tissues were harvested 6 weeks after transfer andthe severity of ileitis determined by a pathologist in a blinded fashion.Results: The severity of ileitis was not significantly affected by isolatedblockade of any adhesion molecule including L-selectin (total score (TS)�11.9 vs. vs isotype TS� 13.9), �7 integrin (TS�13.8 � 2.7), �4�7 integrindimer (TS�12.8 � 2.4), or MAdCAM-1 (TS�15.9 � 1.2), compared tomice treated with isotype antibodies (TS�16.1 � 1). In contrast, simulta-neous blockade of MAdCAM-1 and L-selectin resulted in decreased in-flammation in mice treated during the first week of adoptive transfer(TS�9.8 � 2.4, P�0.05 vs. isotype) and on mice with established disease(TS�8.3 � 1.6, P�0.05 vs. isotype).Conclusions: Additional L-selectin blockade may provide added benefit tocurrent anti-alpha4/alpha4beta 7 integrin blockade strategies (i.e. Natali-zumab, MLN-O2) for the induction and maintenance of remission in CD.

739

NON-SELECTIVE NONSTEROIDAL ANTI-INFLAMMATORYDRUGS (NSAIDs) AND INFLAMMATORY BOWEL DISEASE(IBD): A CRITICAL APPRAISAL OF THE EVIDENCEYuhong Yuan, Ph.D., Changcheng Wang, M.D.,Richard H. Hunt, FACG*. McMaster University Medical Centre,Hamilton, ON, Canada.

Purpose: Non-selective NSAIDs are associated with an elevated risk ofdamage and complications throughout the GI tract. IBD may be associatedwith arthritis for which patients require anti-inflammatory drugs. WhetherNSAIDs should be contraindicated in patients with IBD is controversial butgenerally use is discouraged. We aimed to explore any possible interactionbetween NSAIDs and IBD.Methods: Literature on the relationship of NSAIDs and IBD was reviewedfrom 1970 to May 2003.Results: Sixty-eight relevant articles and abstracts were retrieved. Animalmodels have shown conflicting results on the effects of NSAIDs on theintestinal mucosa. Information from clinical studies is limited and includesseveral case reports and small series of patients reporting onset of IBD,activation of quiescent IBD or exacerbation of IBD with NSAIDs use.There are no good prospective controlled trials conducted in IBD patientsor general populations receiving NSAIDs. Three retrospective studies re-

viewed a total of 127 IBD patients with contrary conclusions on therelationship of NSAIDs and active IBD. Three case-control studies wereconducted in 365 IBD patients including new cases of colitis; NSAIDsusers were interviewed and compared with matched IBS patients or con-trols without colitis. 31%–74% of IBD patients were taking NSAIDscompared with 2%–29.5% of control patients taking NSAIDs (OR1.93–9.1). In 5 small trials in 103 IBD patients taking NSAIDs compared to noanalgesics or non NSAID analgesics (eg acetominophen) from 1–4 weeks,conclusions were inconsistent. No data could be pooled for analysis be-cause trials were either non-randomized or confounded by IBD therapy; notreatment arm had more than 30 patients. No unified definition of IBD,NSAIDs induced colitis or NSAIDs exposure was used in these trials.Conclusions: Available data on IBD and non selective NSAIDs are lim-ited, conflicting and inconclusive. Although NSAIDs are discouraged inpatients with IBD, a well designed prospective or case ontrolled study isrequired, before concluding with confidence that NSAIDs do more harmthan good in IBD patients.

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CDP870, A PEGYLATED HUMANIZED ANTI-TNF ANTIBODYFRAGMENT, OFFERS PARTICULAR BENEFIT TO CROHN’SDISEASE PATIENTS WITH ELEVATED C-REACTIVEPROTEINStefan Schreiber, M.D.*, Paul Rutgeerts, M.D., Alison Innes,Jatin Patel, the CDP870 Crohn’s Disease Study Group. Christian-Albrechts University, Kiel, Germany; Leuven University Hospital,Leuven, Belgium and Celltech Research and Development, Slough,United Kingdom.

Purpose: CDP870 has shown efficacy in patients with active Crohn’sdisease (CD) in a Phase II randomized, placebo-controlled study. Multi-variate analysis identified baseline C-reactive protein (CRP) as predictiveof significant response. A post hoc analysis of this study was performed todetermine the efficacy of CDP870 in patients with baseline CRP �10mg/L.Methods: 292 adult patients with active CD (CDAI score 220–450)received subcutaneous CDP870 (100, 200 or 400mg) or placebo at wks 0,4 and 8. Patients with baseline serum CRP �10mg/L were identified.Clinical response (defined as a decrease in CDAI score �100 or remission[CDAI score �150]) was assessed every 2 wks up to wk 12. Otherendpoints included CDAI scores and serum CRP.Results: In the overall ITT analysis, CDP870 400mg was the most effec-tive dose, inducing statistically significant rates of clinical response andremission compared with placebo, though differences were not significantat wk 12. Only 41% (119/290) patients had baseline CRP�10mg/L. Inthese patients CDP870 400mg induced high rates of clinical response andremission which were statistically significant compared to placebo at alltimepoints (clinical response wk 12: CDP870 400mg 53.1% [17/32] vsplacebo 17.9% [5/28]; p�0.005). Analysis of CDAI scores and CRPconfirmed CDP870 400mg was the most effective dose. CRP concentra-tions were reduced in all active treatment groups as early as wk 2. This wasmost pronounced in the CDP870 400mg treatment group (CDP870 400mgratio to baseline 0.321 [95%CI: 0.196–0.526] vs placebo 0.835 [95%CI:0.634–1.100] and was maintained up to wk 12. In patients with CRP�10mg/L at baseline (n�171) no significant difference between CDP870400mg and placebo was observed for any of the endpoints.Conclusions: The percentage of patients with CRP �10mg/L was surpris-ingly high in this population, which may be characteristic of trials in centerswhere biologics are used. Subcutaneous administration of CDP870 400mgis effective in the treatment of active CD, with a particularly rapid onset andduration of effect seen in patients with baseline CRP �10mg/L. RoutineCRP measurements may be used to identify patients with active inflam-mation who may gain particular benefit from anti-TNF therapy.

S245AJG – September, Suppl., 2003 Abstracts