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Influenza Vaccination Awareness and History in Children with InflammatoryBowel DiseaseJennifer deBruyn, Iwona T. Wrobel

BACKGROUND: The Public Health Agency of Canada recommends annual influenza vaccina-tion for all individuals with chronic immunosuppression (due to underlying disease and/ortherapy) as well as household contacts. OBJECTIVES: To evaluate awareness of influenzavaccine recommendations, and personal and family history of influenza vaccination inchildren with inflammatory bowel disease (IBD). METHODS: Medical care for all childrenwith IBD in southern Alberta (population 1.5 million) is provided at the only tertiary-carecenter for this region, the Alberta Children's Hospital (ACH). All children with IBD followedat the ACH were invited to participate in a study on influenza vaccine immunogenicity. Allparticipants completed a parent/self-administered questionnaire on awareness of influenzavaccine recommendations and personal and family history of influenza vaccination. Dataon demographics, IBD history, and IBD medications were also collected. RESULTS: Sixty-one children with IBD and their families participated in the influenza vaccine immunogenicitystudy and completed the questionnaire. Thirty-seven and 31 families were aware of influenzavaccine recommendations in immunosuppressed individuals and household contacts,respectively. Thirty-one subjects with IBD had previous influenza vaccination; however 4subjects had not received any influenza vaccinations in the last 4 years. IBD subjects whowere aware of recommendations were more likely to have previous influenza vaccination(odds ratio [OR] 6.4; 95% confidence interval [CI] 2.0-20.7). The reasons for no previousinfluenza vaccination in subjects with IBD were: no specific reason (13), “didn't know neededit” (11), needle aversion (4), did not believe vaccine effective (3), afraid of side effects (2),vaccine not available (1), and personal philosophy against vaccine (1). Subjects with diseaseduration ≥ 1 year were more likely to be aware of recommendations (OR 3.6; 95% CI 1.2-11.1) and have previous vaccination (OR 5.9; 95% CI 1.6-17.4). No association was foundbetween immunosuppressive medication use and awareness of recommendations or previousvaccination. Families aware of recommendations for household contacts were more likelyto have previous influenza vaccinations in siblings (OR 7.9; 95% CI 2.3-27.0) and parents(OR 3.0; 95% CI 0.8-11.3). CONCLUSIONS: Families of children with IBD have suboptimalawareness and uptake of influenza vaccination. Physicians prescribing immunosuppressivemedications for IBD need to discuss vaccination for vaccine-preventable diseases, especiallyinfluenza, with their patients.

W1203

Title: A Single-Center Experience with Methotrexate After Thiopurine Therapyin Pediatric Crohn DiseaseBrendan Boyle, Laura Mackner, Christina E. Ross, Soma Kumar, Jonathan Moses, WallaceCrandall

BODY: Thiopurines are a common, effective means of maintaining remission in pediatricCrohn disease (CD). For those intolerant or unresponsive to thiopurines, maintenancetherapy with methotrexate (MTX) may be considered. However, the use of MTX as mainten-ance therapy following thiopurine failure in pediatric CD is less established. The purposeof this study was to examine our experience using MTX as maintenance therapy in patientspreviously treated with thiopurines. METHODS:We identified all patients seen at NationwideChildren's Hospital from 2000-2007 with an ICD code indicative of CD. The chart of eachpatient was reviewed and patients with a confirmed diagnosis of CD, no current infliximabtherapy, a history of thiopurine use prior to MTX, and at least 6 months of follow up afterMTX initiation were included. Reason for thiopurine discontinuation, prior and concomitanttherapies, physician global assessment (PGA), and screening laboratory studies were obtainedat initiation. These outcomes were reevaluated at 6 and 12 months in addition to steroid/infliximab free remission rate, steroid use, progression to infliximab, reason for MTX disconti-nuation, and adverse events (AE). RESULTS: Twenty-eight patients (17 male) with a meanage at diagnosis of 12.2 +/- 3.7 years and mean disease duration of 1.8 +/- 2.0 years wereidentified. Indications for MTX included non-response to 6MP/Aza (11), AE (15), andthiopurine non-adherence (2). At MTX initiation, 3 patients were in steroid free remissionand eleven were receiving steroids. At 6 months, 14 of the original 28 patients (50%) werein steroid/infliximab free remission. Of 27 patients with evaluable date, 3 were receivingsteroids, and 9 had begun infliximab therapy. Three had discontinued MTX secondary tonon-response (2) or AE (1), and 1 did not have evaluable data. At 12 months, 11 of theoriginal 28 patients (39.2%) were in steroid/infliximab free remission. Of the 24 with availabledata, six required steroids and 8 were treated with infliximab. Two additional patients haddiscontinued MTX due to non-response (1) or parental choice (1), and 3 had no evaluabledata. Laboratory studies revealed three patients with transient leukopenia and 4 with transienttransaminase elevation over the 12 month period. CONCLUSION: MTX can be effective asmaintenance therapy for pediatric CD patients who were intolerant of, or unresponsive to6MP/azathioprine, with 50% and 39.2% in steroid/infliximab free remission at 6 and 12months. Approximately one-third of this cohort required escalation to biologic therapywithin the first 12 months following MTX initiation. MTX was well tolerated.

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W1204

Portable Indirect Calorimetry (MedGem) in Pediatric Crohn's DiseaseMark R. Corkins, Steven J. Steiner, Scott Denne

Background: Children with Crohn's disease often have poor growth, and several small studieshave suggested that they have increased metabolic needs. Measurement of resting energyexpenditure may serve as a proxy for disease activity, and may help guide medical andnutritional interventions in children with active Crohn's disease. Aim: To measure restingenergy expenditure using a portable, hand-held device in children with Crohn's disease.Methods: Pediatric patients with active Crohn's were underwent both open circuit indirectcalorimetry and portable indirect calorimetry using the MedGem (Microlife USA, Inc.;Dunedin, FL) on the day of study. Open circuit indirect respiratory calorimetry was performedto measure resting oxygen consumption, carbon dioxide production, and resting energyexpenditure. Measurements were taken over 30 minutes while the patients were quiet andsupine. The MedGem measures VO2 and calculates the resting energy expenditure basedon a fixed respiratory quotient. Over 5 minutes in a sitting position, the patient breathesthrough the MedGem device with a noseclip in place. Resting energy expenditure and VO2were compared between these methods using a paired t-test. Results: Seven patients (meanage 15.2 ± 2.6 yr) were enrolled. The average BSA was 1.6 ± 0.3 kg/m2. No significantdifference was noted in resting energy expenditure and VO2 between the MedGem deviceand open circuit indirect calorimetry. Conclusion: Open circuit indirect calorimetry andportable indirect calorimetry using theMedGem device provide valuable data about metabolicactivity in pediatric patients with Crohn's disease. The portability, ease of use, and shortduration of the MedGem device makes it a valuable device for the assessment of energymetabolism in pediatric Crohn's disease patients.

W1205

How Variable Is the Mayo Score Between Observers and Might This AffectTrial Recruitment or Outcome?Alissa J. Walsh, Oliver Brain, Satish Keshav, Otto C. Buchel, Brent Merrin, MichalRolinski, Sally Thomas, Lydia White, Douglas G. Altman, Simon Travis

Background:The Mayo score for ulcerative colitis(UC) activity has 4 components:stool fre-quency(SF),rectal bleeding(RB),flexible sigmoidoscopy(FS)and physician's global assess-ment(PGA). How interobserver variation(IOV)affects the Mayo score and its impact oncriteria for inclusion or outcome of clinical trials are unknown. Methods:100 patients withUC were seen independently, each on the same day,in random order,by 4 gastroenterologists.Both patient and clinician completed a proforma. A separate clinician performed video-recorded FS on the same day which was later scored by the 4 gastroenterologists. Eachcomponent of the score and total score were calculated for each patient. Comparison wasmade with inclusion criteria for ACT 1&2 trials (Mayo 6-12, endoscopy subscore >2),remis-sion outcome (Mayo <2, no subscore >1). For clinical relevance(CR),scores were categorisedas remission(<2),mild(3-5),moderate(6-8),or severe(9-12) activity and an experienced,blinded clinician independently assigned an appropriate clinical category (ACC) to eachpatient by assessing symptoms, examination, blood results, FS and histology. Quadraticweighted κ statistics assessed agreement within the Mayo score,where disagreements areweighted in relation to their magnitude. Results:Of 100 patients, there was complete agree-ment between 4 clinicians in total Mayo score in 6/96 (4 had no FS), varying by <2 pointsin 84/96, which changed clinical category in 23/84. Overall agreement for CR and ACCwere good (κ=0.88 and κ=0.81 respectively). Between patients and clinicians there was 70%agreement for SF and RB. Between clinicians there was complete agreement in 65% for SF,74% for RB, but only 21% for FS and 45% for PGA. Most disagreement was by one category(median 81%, range 74-93). For inclusion criteria, at least 1 clinician would have included41/96, but all agreed in only 17/41(41%). At least ¾ clinicians would have included 22 andexcluded 67, so there was at least 25% disagreement in 26/96(27%) and 50% disagreement in11/96(11%). 11% had FS score ≥2 but total score ≤5;9.1% had a total score >6 but a FSscore <1. For remission,at least 1 clinician scored <2 in 43/96, but all agreed in only 20/43 (47%) and ¾ agreed in 35/43 (81%). Agreement was not significantly improved by atotal score <1 (at least 1 = 39/96; all agree 20/39; ¾ agree 35/39). Conclusion:There is highvariability in Mayo scoring between observers,despite good agreement on clinical category.Complete agreement between observers for recruitment to clinical trials or outcome occursin <50% and ¾ agreement in about 80% patients. IOV should be considered when calculatingthe power of clinical trials.

W1206

Split-Dose Administration of 6-Mercaptopurine/Azathioprine: A EffectiveNovel Strategy for IBD Patients with Preferential 6mmp MetabolismDavid Q. Shih, Minh Nguyen, Patricio Ibañez, Lola Y. Kwan, Stephan R. Targan, Eric A.Vasiliauskas

BACKGROUND and AIM: 6 Mercaptopurine (MP) and azathiopurine (AZA) are efficaciousin treating IBD. Studies suggest that 6-thioguanine (6TGN) metabolite levels correlate withtherapeutic efficacy, whereas high 6-methylmercaptopurine (6MMP) levels are associatedwith risk of hepatotoxicity and possibly myelotoxicity. A subset of IBD patients exhibitpreferential 6MMP production, characterized by disproportionate elevations in 6MMP, whichmay lead to side-effects of leucopenia, hepatoxicity, and flu-like symptoms. 6MMP overprod-uction and side-effects resolve with dose reduction but the lower dose often fails to suppressdisease activity. We observed that splitting the daily dose of thiopurine (e.g. 50mg BIDrather than 100mg once daily) can reduce 6MMP while maintaining 6TGN levels and clinicalefficacy. The aim of this study is to review the outcomes of thiopurine split-dosing strategyin patients with preferential 6MMP metabolism. METHODS: A restrospective chart review

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