Clinical implications of thiopurine-methyltransferase activity (TPMTe) induction by azathioprine (AZA) treatment in patients with inflammatory bowel disease (IBD)

dose was 226 (0.3 SD) mg/Kg/d Mean MCV increase was 3.9 (5.7 SD) % at 3 months, and 8.7 (9.9 SD) % at 6 moths. TPMTe induction (increase > or = 10% from baseline values to the end of follow-up) occurred in 37.8% of patients between 7 and 30 days after starting AZA No correlation was found between TPMTe or its induction, and treatment efficacy, toxicity or variations in leukocyte, neutrophil or lymphocyte counts. Only MCV increase at 3 and 6 months was significantly and inversely corrdated with basdine and 3 months TPMTe, respectively (p=0.04 and p=0025). Conclusions: Almost 40% of IBD patients induce TPMTe while being under AZA treatment. There is no relationship between TPMTe or its induction and treatment efficacy or toxicity. Only MCV increases depend on TPMTe.

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Clinical Evaluation of a Lateral Flow Test for the Detection of Elevated Fecal Lactoferrin as an Indicator of Intestinal Inflammation James Boone, Dante[ Siseo, David Lyerly, Thomas Walker, Paul Rufo Background: Human lactofernn, an 80 KD glycoproteni, is a component of neutrophil secondary granules and is found m the secretions hydrating mucosal membranes. Duaing intestinal inflammation, activated neutrophils migrate into the lumen and a measurable increase of fecal lactoferrin (FLA) can be detected. Previous studies have demonstrated that elevated FLA can discnminate patients with active inflammatory bowel disease (IBD) from FLAlevelsmeasured in a healthy control population as well as in inactive IBD and in patients vath imtable bowel syndrome (IBS). Aim: To validate a qualitative lateral flow FLA assay developed as a rapid tool for use in physicians' offices for the evaluation and interval assessmentof patients with symptoms of IBD and IBS. Methods: FLA was measured quantitativelyand qualitativdy in 79 fecal specimens from IBD and IBS patients. The study population was eompnsed of 58 Crohn's disease (CD), 18 ulcerative colitis (UC) and 3 IBS patients with an age range of 4 to 51 yrs and gender ratio of 1 to 2.5 (male to female). FLA (ug/g feces) was determined by ELISA using a standard curve of purified lactoferrin. Qualitative analysis for elevated lactoferrin was done by ELISA (IBD-CI-IED using an absorhance cutoff of 0.2 and visually by lateral flow. Active disease was defined by an elevated FLA of 8ug/g feces. Results: FLA was elevated in 48 of 74 specimens tested from IBD patients. FLA measured in patients with active CD and UC was 278 + 0.36 and 1217-+ 534, respectively (mean-+SE). In contrast, FLA measured in feces from patients with inactive CD, UC and IBS was 1.43 + 0.35, 4.07 -+0.99 and 1.83 -+0.51, respectively. The lateral flow assay displayed a sensitivity, specificity and overall correlation for detecting an FLA greater than/equal to 8ug/ g feces (indicative of active intestinal inflammation) of 100, 94 and 98%, respectively. Conclusion: Our results demonstrate that the lateral flow assay performs equivalently to the IBD-CHEK in screening for the presence of intestinal inflammation. This test is a simple ten minute assay, making it suitable for use in the physicians' office/clinic setting.

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Carbohydrate Malabsortion and/or Intolerance in Inflammatory Bowel Disease Ursula Estada, Miguel Mingnez Sr., Pedro Almela, Vicente Hemandez, Belch Herrerns, Cirilo Amoros, Vicente Sanchiz, Francisco Mora, Adolfo Benages Background: Lactose malabsorption has been studied on patients with inflammatory bowel disease (IBD), but no references of fructose malabsorption have been found. Objectives: To assess the prevalence of malabsorption/intolerance to lactose and/or fructose on patients with IBD. Patients and methods: Prospective study on 62 patients (33M/29F) with ulcerative colitis (UC), 63 patients (29M/34F) with Crohn's disease (CD) and 32 (13M/19F) healthy volunteers (CG). Fructose (FRU) and lactose (LAC) absorption was assessed by determining levels of end-expiratory breath H2 with a gas chromatograph every 30 rain thereafter for 3 hours after an oral intake of 25g of carbohydrate. Symptoms were evaluated before, during and 24h after the test with a specific score protocol. Localization, seventy (CDAI, Truelove index) and surgical treatment were evaluated. Statistical differences between groups were analyzed by means of the Chi-square test for qualitative parameters and values of p<0.05 were considered as statistically significant. Results: Twenty-four patients (5 CG, 8 UC, 11 CD)were excluded since they did not produce H2 after lactulose challenge. Prevalence of LAC and/or FRU malabsorption is shown in the Table. The presence of symptoms of intolerance to LAC and FRU was more frequent in UC and CD than in CG In UC, during the LAC test was 32% and 44% after 24h, during the fructose test was 17% and 26% in the next 24h. In CD group, dunng the LAC test was 19% and 62% 24h afterwards, in the case of FRU was 23% during the test and 44% in the next 24h. In CG, intolerance during the LAC test was 7% and 19% after 24h, during the FRU test 4% and 7% 24h afterwards (p<0.05 in all cases). No differences were found in absorption and tolerance depending on the presence or not of ileo-cecal resection in CD. Conclusions: Prevalence of lactose malabsorption is similar in IBD patients and in healthy subjects. Fructose malabsorption is higher in CD, independently of the presence of fleo-cecal resection. IBD patients suffer intolerance to both carbohydrates more frequently than healthy subjects."

S1322 Can Mucosal Healing in IBD Patients be Determined by Normalization of Faecal Calprotectin ? Ame G. Roseth, Erling Aadtand BACKGROUNDSaverymuttu and coworkers have elegantly demonstrated that [BD patients had increased excretion of llllndium-labefled granulocyte in stools. They found a good correlation between this marker and the disease activity in such patients. However, they also found significantly elevated levels among patients in clinical and biochemical remission which demonstrated substantial mucosal inflammatory activity despite no clinical sign of disease activity. Furthermore it has been shown that 1BD patients with such "smoldenng" inflammation often develops a relapse in the near future but among patients with complete mucosal healing, very few relapsed. Calprotectin is a granulocyte marker can be assessed in small stool samples by ELIS& normal value is < 50mg/L. Several studies have demonstrated good correlation between calprotectin and the excretion of 111-Indium labeled leukocytes. Furthermore, patients with elevated calprotectin (>250 rag/1.) developed a relapse more rapidly in comparison to those with lower values. Calprotectin is a commonly used marker of inflammation in our department to follow up IBD patients as they go into remission. MATERIALSAND METHODS: This study comprised 10 patients treated for clinically"and endoscopicafly active iBD, 6 with UC and 4 with CD. one male and nine females, age 2770 years and disease duration froml-10 years. They agreed to a second colonoseopy indud. t. ileum when the faecal calprotectin levels normalized for determination of possible subclinical inflammation. Inflammatory actiwty was determined by endoscopic and hlstologic evaluation of the mucosa following accepted criteria. RESULTS: Median faecal calprotectin during active disease was 2411 mg/k (Cl 1711-4524) and during remission it was 28 mg/ k (CI 13-36) p<0.000 ] The endoscopic and histologic evaluation both demonstrated normal mucosa with no signs of inflammatory activity. CONCLUSION: In this study we have shown that normalization of faecal calpmtectin indicates mucosal healing in pts with IBD. This finding may have clinical application since mucosaI healing in such pts seems to have prognostic implications, and can be a goal for medical treatment in the future. If this holds tree, assessmem of faecal calprotectin may replace costly and unpleasant colonoscopies for the determination of mucosal healing in the near future This material will be further expanded and presented at the DDW.

Prevalence of lilalabsoel~Onto Lactose and/or Fructose LACTOSE FRUCTOSE Control Group (n.24) 8 (30%) 5 (19%l Ulcerative Colitis (n.50) 14 (26%) 4 (7%) C,robn's Diumm (n.51) 38 {35%) 27 {52%)** * p<0.05 with respectto CG; + I)<0.05with respectto UC. Chi-squetetest

BOTH 1 (4%) 2 (4%) 10 {20%)+

S1325 Repeat Single Photon Computerised Tomography (SPECT) White Cell Scanning to Monitor Efficacy of Treatment in Inflammatory Bowel Disease (IBD) Andrew Poullis, Andrew G. Irwin, Michelle Dearing, Charlie Gordon, Jeff Gane, Alan Britten, Susan Heenan, Paresh Solo, William VennarL Douglas Maxwell Introduction: We previously demonstrated that SPECT scanning correlates more strongly" with histological grading of inflammation severity than clinical activity scores in active 1BD. SPECT scans provide non-invasive and accurate quantification of IBD activity in both large and small bowel and may be useful in the objectwe evaluation of IBD activity Aims: To evaluate the effectiveness of sequential SPECT scanning in monitoring the response to treatment of active IBD in comparison with clinical activity scores Patients: Nine subjects with active Ulcerative colitis (UC) (5 mild, 3 moderate, 1 severe) and 9 subjects with active Crohns disease (CD) (5 mild, 3 moderate, 1 severe) were studied. Methods: 99mTc-white ceil SPECT scanning was camed out immediately prior to and 2 weeks after initiation of anti-inflammatory treatment. Disease activity scores for UC (Powell-Tuck index (PTI) and Mayo clinic score (MCS)) or CD (Crohn's disease activity index (CDAI), Harvey gradshaw Index (HBI) and van Hees activity index (VHAI)) were calculated at baseline and 2 weeks after initiating therapy. SPECT scans were analysed for maximal bowel uptake expressed as a fraction of mammal marrow uptake (SPECT score): the same region was re-assessed in the 2nd scan Assessors were blinded to clinical details and clinical activity scores. Results: The SPECT score improved in 8/9 (89%) with CD and 7/9 (78%) with UC. In the CD subjects there was agreement for direction of change in SPECT score and CDAI in 7/9 (78%), HBI in 4/9 (45%), and VHAI in 6/9 (67%). In UC subjects there was agreement for direction of change in SPECT score and PTI in 7/9 (78%) and MCS in 6/9 (67%). The agreement was not affected by disease severity. Conclusion: Non-invastve repeated SPECT white cell scanning may be a more reliable and ohiective method to monitor the antiinflammatory efficacy of novel treatments for active IBD than partly subjective clinical scores. Clinical scores in IBD agree poorly with oblective measures of bowel inflammation.

S1323 Clinical Implications of Thiopurine-Methyhransferase Activity (TPMTe) Induction by Azathioprine (AZA) Treatment In Patients With Inflammatory Bowel Disease (IBD) Eugeni Domenech, Esther Garcia-Plandla, Lourdes Fluvia, Isabel Bernal, Eduard Cabre, Miquel GassuU Background: In transplant recipients, AZA treatment seems to induce TPMTe. Those patients with a higher and earlier TPMTe induction, have the lowest incidence of acute transplant rejection, suggesting a better immunossuppresion (Mircheva et al. Transplantation 1995). Aims: To evaluate whether AZA treatmem induces TPMTe in [BD patients, and if baseline TPMTe or its induction correlate with AZA efficacy or loxicity. Patients and Methods: Thirtyseven 1BD patients with baseline TPMTe >5 U/ml RBCs were prospectively included All patients started AZA (2-2.5mg/Kg/d) because of steroid-dependence (DEP) in= 24) or for prevention of CD recurrence (REC) (n = 13) TPMTe was measured at baseline, 7 days, 1, 3, and 6 months after starting AZA Patients followed clinical and analytical contrds at the same periods, and every 3 months until 12 months of follow-up. In the DEP group, dioicaI response (defined as complete steroid withdrawal and maintenance of clinical remission) was evaluated at 6 and 12 months. Results: Only 5 cases of AZA toxicity were registered (1 neutropenia and 4 lymphopenia), that did not require treatment withdrawal. Twentythree out of 24 DEP patients, achieved response at 6 months, and 21 remained in remission at 12 months (87.5%). Mean baseline TPMTe was 1339 (3.42 SD) U/mL RBCs. Mean AZA

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