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sof disease was 12.9 ± 11.1 years. Mean BMI was 26.5 ± 5.3. Patients were stratified by BMI:underweight (BMI<20) 9.6%; normal weight (BMI 20-24) 24.3%; overweight (BMI>25)41.7%; and obese (BMI>30) 24.3%. There were no significant differences among the 4 BMIcategories in age (p=0.265), race (p=0.118), sex (p=0.731), or duration of disease (p=0.832).Underweight patients had more upper GI modifiers (underweight: 36.4%, normal weight,17.9%, overweight 14.6%, obese 0.0%; p=0.023) with a decreasing prevalence of upper GImodifiers with increased weight (p=0.003). In multivariate analysis comparing obese tonormal weight patients, obese patients were more likely to have colonic disease (OR 8.64,p=0.047) but were similar in disease behavior and perianal disease. There were no significantdifferences in disease behavior, disease activity and perianal disease among the individualBMI categories. Vitamin D insufficiency (20 mg/dL < 25-OHD < 29.9 mg/dL) and deficiency(25-OHD < 20 mg/dL) were noted in 38.9% and 35.2%, respectively. Overweight and obesepatients were more likely to have low Vitamin D levels than underweight patients (83% vs33%, p=0.004). Conclusions: The majority of patients (66%) in our cohort were eitheroverweight or obese in correlation with national trends. Obese patients were more likely tobe vitamin D deficient and have disease limited to the colon. Underweight patients weremore likely to have upper GI modifiers suggesting that disease location plays a role in weightmodulation. This finding may be from malabsorption or symptoms associated with upperGI symptoms like pain or anorexia.

Su1371

High Infliximab Trough Levels Are Associated With Impaired Quality of Lifein IBD Patients in Clinical and Biochemical Remission on Maintenance IFXTherapyM. Lowenberg, Johannan F. Brandse, Laura M. Vos, Cyriel Ponsioen, Gijs R. van denBrink, Geert R. D'Haens

Background: Preliminary evidence suggests a therapeutic window for infliximab (IFX) troughlevels (TL's) in patients with inflammatory bowel disease (IBD). It remains unknown ifhigher or presumably ‘supra-therapeutic' TL's are associated with adverse effects. The aimof this study was to identify an association between high TL's, side effects of IFX treatmentand quality of life. Methods: We performed a cross-sectional study in IBD patients in clinicaland biochemical remission. Clinical remission was defined as HBI<5 for Crohn's disease(CD) and CCAI<5 for ulcerative colitis (UC). Biochemical remission was defined as a fecalcalprotectine < 250 microgram/gram. IFX TL's and biochemical markers to rule out alternativediagnosis for fatigue were assessed (Hb, Ht, TSH, CRP and vitamin D). Quality of life wasassessed by IBDQ and SF-36. Fatigue and joint pain were measured by VAS scores and forskin lesions a skin questionnaire was completed. The patient cohort was separated in patientswith ‘therapeutic' (IFX TL 3-7 ug/ml) and ‘supra-therapeutic' (IFX TL >7 ug/ml) drug levels.Patients were unaware of their TL when they completed the questionnaires. Results: Thirty-seven out of 81 screened IBD patients (26 CD and 11 UC) met all the criteria for clinicaland biochemical remission. The median CRP, fecal calprotectine and haemoglobin concentra-tion was 0.7 mg/l, 63 microgram/gram and 8.7 mmol/l, respectively, while median IBDQwas 180. Therapeutic TL's were found in 29 out of 37 (78%) patients, whereas 8 out of 37(22%) patients had supra-therapeutic TL's. Antibodies to IFX were undetectable in allpatients. Inverse correlations between TL concentrations and quality of life determinantswere found for IBDQ (-0.370, P<0.05) and the following domains of the SF-36 questionnaire:social (-0.359, P<0.05), pain (-0.406, P<0.05) and perception (-0.380, P<0.05). Patientswith supra-therapeutic TL's had lower SF-36 scores, compared to the therapeutic TL group,in 5 out of 9 domains (figure), of which two were significant: social (50 versus 70; P<0.05)and pain (67.5 vs. 88; P<0.05). The two groups scored equally for the remaining 4 SF-36domains. Although not statistically significant, patients with supra-therapeutic TL's reporteda somewhat lower quality of life by IBDQ (175 vs. 185; P=0.30) and more joint pain (13.5vs. 6.0; P=0.33). Conclusions: IBD patients who were in clinical and biochemical remissionwith supra-therapeutic IFX TL's had an impaired quality of life compared to those withtherapeutic IFX TL's. Future trials should determine whether dose de-escalation wouldabolish these side effects.

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Risk Factors for Rescue Therapy in Crohn's Patients on Combination TherapyAfter Discontinuation of the ImmunomodulatorMonika Fischer, Sarah C. Campbell, Cynthia S. Johnson, Debra J. Helper, Michael V.Chiorean

Background: The usefulness of combination therapy in non-IM Naive patients and theoptimal length of dual therapy are still debated. The aim of our study was to determine theproportion of patients requiring rescue therapy and risk factors associated with diseaseflare after de-escalation of the IM. Patients and methods: Crohn's patients in remission oncombination therapy were identified from a large single-center database between 2002 and2008. Patients on infliximab who had their IM (azathioprine or methotrexate) stopped ordecreased by more than 50% in the absence of adverse events were considered eligible for

S-450AGA Abstracts

the study. Rescue therapy was defined as steroid use, biologic dose escalation or switchingto another anti-TNF inhibitor, resumption of IM, hospitalization or surgery. Associationbetween clinical variables and time until rescue therapy was analyzed using Cox-proportionalhazards models. Results: Of the 321 patients in the database receiving biologic therapy, 43patients in remission at the time of de-escalation were included. Of these patients, 86%were non-IM Naive. The median duration of follow-up was 61.6 months (5.4-129.5). Themean age was 39.3 (±15.0), 39.5% were males, 93.0% whites, 25.6% smoking history, themedian disease duration was 86.0 months (8.0-416.9), and 23.3% had previous surgery.The median duration of remission on combination therapy prior to de-escalation was 12.0months (4-74). Thirty-one patients (72.1%) required rescue therapy during follow-up. Themedian duration of remission after de-escalation was 28.1 months, 95% C.I. (10.0, 52.9).On multivariable analysis, age < 16 years compared to age > 40 years at the time of thediagnosis was a significant risk factor for rescue therapy HR= 4.55, (1.18, 17.62), p=0.0282.Age 16-39 was a borderline risk factor compared to age at least 40 years HR = 2.99, (0.93,9.56), p=0.0654). When methotrexate was used in combination with infliximab instead ofazathioprine, it was a risk factor for rescue therapy HR = 3.37, (1.14, 9.96), p=0.0279.Duration of combination therapy less than 6 months was also a risk factor HR= 5.68, (1.58,20.36), p=0.0077. Other clinical variables including age at de-escalation, sex, race, smoking,prior surgery, and disease location, duration and behavior were not associated with the riskof rescue therapy. Conclusion: A large proportion of patients required rescue therapy afterde-escalation of IM. Young age at the time of Crohn's disease diagnosis, use of methotrexatecompared to azathioprine, and short duration (< 6 months) of combination therapy wereassociated with increased risk for rescue therapy.

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Low Dose Azathioprine With Allopurinol Co-Therapy Without MetaboliteProfiling Is More Effective and Safer Than Full Dose Azathioprine forInflammatory Bowel Disease Patients: A Large UK Centre ExperiencePanagiotis Stamoulos, Evangelos Stournaras, Clare Bull, Matthew Cowan, GaryMackenzie, Jonathan Stenner, Sally A. Coulthard, Azhar R. Ansari

Introduction The effectiveness of full dose azathioprine (FDA) for inflammatory bowel disease(IBD) has been questioned in recent scientific literature. A popular strategy to improve itsoutcomes recommends the use of low dose azathioprine with allopurinol co-therapy (LDAA)for patients with specific thiopurine metabolite profiles, so called "hypermethylators" (30%of non responders). Aim The aim of this study was to determine the safety and efficacy ofLDAA without thiopurine metabolite profiling. Methods Medical records of IBD patientstreated with LDAA were retrospectively analysed. Patients who had poor response and/orside-effects to FDA were offered LDAA by all Consultants whilst a single IBD physician alsooffered LDAA to thiopurine-Naive patients after careful counselling. Azathioprine dose wasreduced to 25% of the thiopurine methyl transferase (TPMT) adjusted dose (0.5mg/kgfor TPMT wild type and 0.25mg/kg for TPMT heterozygotes) followed by conventionalhaematological monitoring. Patients who were suspected to be non-adherent had metabolitesmeasured prior to initiating LDAA. Full response (FR) was defined as steroid free remission(Harvey Bradshaw index ≤3, Truelove-Witts normal) for greater than 3 months after a 3month induction period for LDAA. Results Of 300 patients on LDAA, adequate data wasavailable for 294 patients. A positive response was seen in 226 patients: full response(FR,207) and partial response (PR,19). The remaining patients were non-responders (NR,68). Non response to FDA was the commonest indication (n,118) for switching to LDAA(table 1). Overall, positive response to LDAA was seen in 76.9% of patients (84.6% in 1st

line LDAA and 74.2% in those who switched to LDAA). Haematological indices confirmedsignificant correlations of erythrocyte sedimentation rate, white cell count, neutrophil count,haemoglobin levels and platelet count with clinical response (table 2). Myelotoxicity occurredin 5 patients (all NR, WCC >2 and <3.5) and 12 patients had mild asymptomatic hepatotoxic-ity (ALT<300) which resolved by increasing allopurinol to 200mg in 9 patients (all FR).Time on treatment: 208 patients took LDAA for more than twelve months with a medianlength of therapy of 24 months. Conclusion Appropriately dosed LDAA therapy delivers atherapeutically effective dose of azathioprine without the need for dose escalation. It alsoappears to be more effective, better tolerated and less likely to cause haematological disturb-ance than FDA. We believe these results raise doubts about the need for thiopurine metabolitelevel profiling prior to using LDAA, as this approach may limit the wider use of thissuccessful therapy.

Table 1