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Collagenous Colitis Associated with Proton Pump Inhibitors (PPI) Aruna Dias, Wendy Thurrell, Patrick Wheeler

Introduction: Collagenous colitis (CC) is a chronic diarrhoeal illness of unknown aetiology characterised by endoscopically normal large bowel mucosa but on histological analysis there is a distinct, thickened subepithelial collagen band measuring 10 ~nt or more and chronic inflammatory" infiltration of the lamina propria. Certain drugs, such as non-steroidal anti-inflammatory drugs have been associated with it but only two case reports have impli- cated lansoprazole (Wilcox GM et alJ Clin Gastroentero12002; 34(2): 164-166 and Thomson RD et al Am J Gastroenterol 2002; 97(11): 2908-13). Method: The study was a retrospective study looking at the records and histology of all patients diagnosed with CC. All patients were being investigated for chronic diarrhoea and had colonoscopy. The records were analysed to see whether patients had been on PPIs prior to developing bowel symptoms. To act as control subjects, an equal number of age and sex matched patients who had bowel symptoms but otherwise normal histology and patients with ulcerative colitis were included. Their drug history was also scrutinized for PPI usage pnor to developing their symptoms. Results: 11 patients had a diagnosis of CC and were included in this study (male = 4), mean age 70.5 years (SD 13.0), and range 55-86.7 patients had been on PPIs, lansoprazole (5) and omeprazole (2), prior to developing diarrhoea (male = 3), mean age 76.3 years, SD 11.3, and range 56-86 years The median time to developing symptoms after being on the PPI was 2 months. 6 out of the 7 patients (85%) expenenced an improvement in their bowel symptoms on stopping the PPI. 4 patients were not any PPls (male = 1), mean age 605 years, SD 9.7, and range 56-75. Of the controls, only one of the normal matched patients had been on any PPI (lansoprazole) before developing diarrhoea. None of the UC patients had been on PPIs pnor to them being diagnosed with inflammatory bowel disease. Conclusions: 7 out of 11 (64%) of patients with CC had been exposed to PP[ prior to developing CC. This finding along with that of improvement in diarrhoea after stopping the PPI adds credence to the argument that in these patients CC may have been drug associated. There was a notably significant age difference between the two groups of patients with CC; mean age of the PPI group was 76 3 compared to 60.5 in the non-PPI group Perhaps older patients are more susceptible to this condition, especially if drugs are implicated.

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Optimal Crohn's Disease Activity Index (CDAI) Response Criteria is Defined by Decrease >100 Points Bruce E. Sands, A. Hilary Steinhart, James D. Lewis, Steven B. Hanauer, Tore Persson, William J Sandbom

Background: The CDAI is widely used to judge efficacy in clinical trials, but various dehmtions of response are employed. We explored the effect of CDAI response definitions on study efficiency. Methods: We analyzed primary CDAI data from studies of budesoinde 9 mg/d vs. placebo (Tremaine, Greenberg), mesalamine 4 gm/d (Thomsen), and prednisnlone 40 mg (Rutgeerts, Campieri) according to 9 definitions of response: decrease from baseline by 50, 70, 100, or 150 points (A, B, D, H); decrease by 25% from baseline and by 70 or 100 points (C, E); CDAI <150 (I) plus decrease by 70 or 100 points (F, G). Differences in response rates among groups were analyzed by one-way ANOVA of percent responding. Response definitions were ranked according to ability to maximize effect difference between treatment arms. Results: Differences in treatment arms were maximized by response defini- tions that incorporated a decrease from baseline CDAI by ->100 (conditions D and E, followed by G). There was no added advantage to including decrease by ->25% or to -<150 in this definition of response. Decrease by 50 points yielded the smallest treatment difference, tollowed by 70 point decrease. Decrease by 150 points minimized placebo response, and produced acceptable effect differences, similar to condition G. Conclusions: Clinical trial efficiency is optimized by using a response cntenon of decrease from baseline CDAI by -> 100 points.

Effect differences for CDAI conditions defining response

Effect Differ. 9 mg w. Placebo 9 mg vs. Mesal. ences azine 9 m9 vs. Prednlsolone Study Greenberg Tremalne Tlmmsen Rutgew?s Camp/eel

Condition A 30 6 18 -12 -5 CocKIItfon B 33 7 18 -14 -7 Condition C 37 11 20 -16 -6 Condition D 39 22 17 -19 -6 Condition E 39 22 17 -19 -6 Condition F 29 16 24 -13 -12 Condition G 29 18 20 -22 -10 Condition H 38 t4 9 -28 -10 Condition I 30 17 25 -13 -10

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A Population Based Case Control Study of Serological Response to Mycobacterium Paratuberculosis in IBD Charles N. Berustein, James F Blanchard, Patricia Rawsthome, Michael T. Collins

BACKGROUND; There is renewed enthusiasm for exploring the possibility that Mycobacte- rium paratuberculosis (Map) may be causative in Crohn's disease (CD). Map is an increasingly common infection among the cattle of Manitoba and elsewhere in Canada and US. OBJEC- TIVE: To determine if CD subjects are more likely to be seropositive than controls. Controls Include ulcerative colitis (UC), healthy controls (HC) or sib controls. METHODS: Using our population-based University of Manitoba Inflammatory Bowel Disease Research Registry we recruited CD and UC subjects between 18-50 years for a study involving detailed question- naires and venipuncture. We accessed the population-based databases of Manitoba Health (single provincial health insurer) to get age, gender and geography matched controls to our

IBD population. We asked enrolling IBD subjects for potential sib controls. We used an ELISA for serum antibodies to Map initially developed in cattle but adapted for human use (IDEXX Lab). All sera were run in duplicate with positive and negative human controls. RESULTS: HC (n=407) were more likely overall to be females (71.3%) than either CD (n = 286) (60.6%) or UC (n = 140) (47.9%), (p<0.O001), and were slightly older (HC = 40.1 yrs, CD=37.2 yrs, UC=37.9 yrs) (p<0.05). The groups were geographically matched (urbanites; HC= 60.9%, CD=62.7%, UC=71.1%, p=NS). The Map+ve rate was CD=37.4%, UC=33.6%, HC=33.9% and sibs=36.4% (n= 143). The mean OD in Map +ve subjects was no different between groups. In CD, Map +ve vs Map-ve were more likely to be urbanites (71.6% vs 57.9%, p=0.03). In UC, Map+re vs Map-ve were more likely to be temales (61.7% vs 40.9%, p=0.01). In HC there was no difference by gender or geographic residence between Map + ve and Map -re. For sibs there was no correlation between Map + ve or -ve rate and the status of the corresponding IBD affected sib. CONCLU- SIONS: In this population-based case control study HC were slightly more likely to be female and were slightly older than CD or UC. However, these groups and sib controls were all about 35% Map + ve. The seroconversion ntay occur in adulthood since there was no correlation between CD and UC or sib Map status. This study does not support Map as an etiology of CD. Supported in part by CIHR and CCFC

Results for CD, UC, IIC of Map se~oprevalence, gender, urban living, age

Map+VE %female %urban mean age CD 37.4% 60% 63% 37.2 gc 33.6% 48% 71% 37,9 HC 33.9% 71% 61% 40,1

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Quality of Life after Pelvic Pouch Surgery is Comparable between Patients with Colitis-Associated Neoplasia and Symptomatic Ulcerative Colitis David E Stein, Feza H. Remzi, Jason Connor, Miriam Preen, James M. Church, Victor W. Fazio

PURPOSE: Many patients with familial polyposis (FAP) are asymptomatic preoperatively. They tend to report a poorer quality of life (QOL) after pelvic pouch surgery than patients with ulcerative colitis (UC). We hypothesized that asymptomatic UC patients requiring surgery for dysplasia or cancer would similarly have a poorer quality of life than patients with symptomatic UC. This may negatively impact surgical referrals for colitis associated dysplasia. METHODS: A review of our prospectively maintained pelvic pouch database was performed. Pauents with a surgical indication of dysplasia or cancer only, were compared to those with surgical indications of medical intractability, acute colitis, steroid dependency and hemorrhage. Generalized linear models were used to compare Cleveland Global Quality of Life scores and functional outcomes at 1, 3, 5 and l0 years. The models were adjusted for age at surgery, year of surgery, gender and anastamosis type. RESULTS: 1,759 patients are included in the study, 1,614 patients In the symptomatic group (S) and 145 with dysplasia/cancer (A). Mean follow-up (FU) time was 6.2 years in each group. Mean QOL score at 1 year was 0.81 in S and 0.82 in A (p = 0.13). Scores remained high and comparable throughout the FU period. There were no statistically significant differences in quality of life, health, energy or happiness. There were no significant differences in bowel movements per day or night, urgency, incontinence, pad usage, or dietary, social and sexual restrictions. There was a significant difference In nighttime seepage with a probability of 0.57 In A and 0.30 in S at 3 and 5 years (3 yr FU p=0.02; 5yr FU p=0.006). There was also increased usage of anti-diarrheal medicine in A (3 yr FU p=0.01; 5 yr FU p=0.O02; 10 yr FU p=0.009). CONCLUSION: Asymptomatic patients with colitis associated neoplasia are unlike those with FAP, In that QOL is not affected by surgically induced detenoration of bowel function. Surgical referral for patients with colitis associated dysplasia should be encouraged, as they can be reassured that they will have a good QOL after pelvic pouch sur- gery

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The Association Between ]BD and Seropositivity to Measles, Mumps and Rubella viruses: A Population-Based Case-Control Study James F. Blanchard, Patncia Rawsthome, Charles N. Bernstein

BACKGROUND: There has been much interest regarding the potential role of exposure to measles and mumps and 1BD. OBJECTIVE: To assess whether serological evidence of pnor exposure to measles, mumps and rubella is associated with IBD. METHODS: A population- based case-control study was conducted. IBD cases (aged 18-50) were recruited from the population-based University of Manitoba Inflammatory Bowel Disease Research Registry. Controls (aged 18-50) were selected at random from the population-based Manitoba Health registry which includes all persons eligible for health insurance in the province (over 95% of Manitoba's residents). Data were collected by a structured interwew and collection of venous blood samples. Serological assessment of IgG seroposirivity to measles, mumps and rubella was done using a semi-quantitative ELISA. Measurement of association was performed using odds ratios. Adjustment for age, sex and urban residence was performed using logistic regression. RESULTS: Overall, serological data were available for 277 Crohn's disease (CD) cases, 155 ulcerative colitis (UC) cases and 353 non-IBD controls. Controls were slightly older (mean age, 40.1 years) than CD cases (mean age, 37.0) or UC cases (mean age, 37.8). Controls were also more likely to be female (72%) than CD or UC cases (61% and 50%, respectively). A similar proportion of controls and cases lived in urban areas (controls 58%, CD cases 52%, UC cases 62%). Overall, controls were more likely to be seroposirive to measles (98.0%), mumps (78.4%) and rubefia (97.8%) than were CD cases (94.6%, 73.0% and 92.1%) or UC cases (94.5%, 73.3% and 92.4%). After adjustment for age, sex and urban residence, there was no significant association between measles or mumps seropositiwty and either CD or UC (Table). There was a significant inverse association between rubella seropositivity and CD, particularly among males. CONCLUSIONS: This study provides no evidence for a positive association between exposure to measles, mumps or rubella and IBD.

AGA Abstracts A-206