5-ASA Use Research Articles

Optimizing clinical use of mesalazine (5-aminosalicylic acid) in inflammatory bowel disease

Mesalazine [5-aminosalicylic acid (5-ASA)] has been used for over 30 years in the treatment of inflammatory bowel disease (IBD). It is a highly effective, safe, and well-tolerated drug for treatment of mild to moderate ulcerative colitis, which represents most patients with this disease. Recent studies of patient adherence to 5-ASA therapies in ulcerative colitis have highlighted the need for regimens that enable long-term compliance to significantly reduce the risk of troublesome and debilitating flares in the short term, and possibly colon cancer in the long term. Indeed, much of the recent innovation in clinical use of 5-ASA in colitis has come from studies of novel delivery mechanisms and simplified oral dosing schedules. These studies have provided much needed clarity on essential matters such as starting dose, dose escalation, and efficacy in terms of the ideal clinical endpoint - mucosal healing. Various manufacturers are re-evaluating their products to determine the safety and efficacy of such dosing regimens. Although once widely employed in the treatment of Crohn's disease (CD), the accumulated body of evidence now suggests that there is a much more limited role for 5-ASA in this particular form of inflammatory bowel disease. Recent 5-ASA randomized-controlled trials, comparative studies, and outcomes research have led to refined treatment strategies and awareness for practitioners to better inform, engage and facilitate patients in optimal use of 5-ASA in inflammatory bowel disease.

A Distinct Mechanism for Reflux in Patients With Cystic Fibrosis: A Study Using High Resolution Manometry-Impedance

neoplasia. Cox proportional hazard regression analysis was used to calculate the risk of advanced neoplasia in patients with and without thiopurine or 5-ASA use. Results: A total of 2605 patients with a confirmed IBD diagnosis were included in this study. Of these, 981 patients (38%) used 5-ASA, 315 patients (12%) used thiopurines, 459 patients (18%) used both 5-ASA and thiopurines and 850 patients (33%) used none of these drugs. No statistically significant differences were found for type of IBD, gender, age, duration of IBD and extent of IBD between these groups. Thirty-one patients (1%) developed advanced neoplasia during 16,568 person years of follow-up. Of these, 12 patients (39%) had used 5-ASA, 2 (7%) thiopurines and 1 (3%) both drugs. Increasing age and disease involvement of more than 50% of the colon were associated with an increased risk of developing advanced neoplasia (adjusted hazard ratio (HR) 1.07, 95% confidence interval (CI) 1.04-1.11 and adjusted HR 5.88, 95% CI 2.00-17.3, respectively). Thiopurine use was associated with a significantly decreased risk of developing advanced neoplasia (adjusted HR 0.10, 95% CI 0.01-0.73). 5ASA therapy had also a protective effect on developing advanced neoplasia, but this was not statistically significant (adjusted HR 0.51, 95% CI 0.20-1.26). Conclusion: Thiopurine use protects colitis patients against the development of advanced neoplasia. The effect of 5ASA appeared to be less pronounced.

The medical management of inflammatory bowel disease in primary care: the north bristol experience

IntroductionEvidence suggests that Aminosalicylates (5-ASA) have a chemopreventative effect in reducing rates of CRC in patients with colitis.1 It is recommended that patients should be maintained on a dose of...

Medical Therapy of IBD in the First Year After Diagnosis: Preliminary Results from the Ocean State Crohnʼs and Colitis Area Registry (OSCCAR)

Purpose: The Ocean State Crohn's and Colitis Area Registry (OSCCAR) is a novel population-based, prospective inception cohort of patients with inflammatory bowel disease (IBD) in Rhode Island. The frequency of medications used to treat IBD during the first year after diagnosis was analyzed with a focus on steroids, immunomodulators and biologics. Methods: Residents of Rhode Island with newly diagnosed Crohn's disease (CD), ulcerative colitis (UC), or indeterminate colitis (IC) were eligible for enrollment beginning January 1, 2008. Diagnosis of IBD was confirmed using criteria from the NIDDK IBD Genetics Consortium. Individuals diagnosed before January 2008, unwilling to provide consent, and those imprisoned or pregnant at diagnosis were excluded. Research assistants collected demographic data, medical history and disease related information, quality of life and disease activity questionnaires, blood, urine and stool samples, with quarterly follow-up in the first year, then every 6 months. 97 of 98 gastroenterologists/colorectal surgeons in RI and 11 in MA agreed to refer patients. Practice billing data were queried and chart reviews were conducted to capture missed referrals. IRB approval was obtained. Results: For enrolled patients, medical therapy during the first year is summarized in tables 1 & 2. 5-ASA was the mainstay of therapy for UC, and a high rate of 5-ASA use was observed in CD. The rate of immunomodulator use was much higher in pediatric compared to adult patients (both CD and UC). CD patients were more likely to be on an immunomodulator or anti-TNF agent compared with UC patients. A substantial percentage of patients were started on anti-TNF therapy early after diagnosis. Conclusion: Among patients captured in this prospective, inception cohort from RI, different patterns of medication usage are seen in adult and pediatric patients, as well as in UC and CD. More than half of patients were exposed to steroids in the first year after diagnosis. A large portion of CD patients were on 5-ASA despite the lack of evidence supporting its use for this indication. Long term follow-up of these patients will yield insight into prescribing patterns and clinical effectiveness of various IBD therapies. Funding:CCFA/CDC 5U01DP000340-03 and NIH 1R21DK078555-02.Table: OSCCAR: medication use in patients with Crohn's diseaseTable: OSCCAR: medication use in patients with ulcerative colitis and indeterminant colitis

Clinical Presentation and Diagnosis of Intestinal Adenocarcinoma in Crohn’s Disease: Analysis of Clinical Predictors and of the Life-Time Risk

BackgroundLate diagnosis of cancer in CD often occurs, and the prognosis is poor. The primary aim of this study was to assess the relationship between clinical presentation and diagnosis of intestinal adenocarcinoma in CD; the secondary aim was to evaluate the timing of cancer occurrence in CD patients. Patients and methodsMedical records of 12 consecutive patients with intestinal adenocarcinoma in CD and of 79 consecutive CD patients undergoing bowel surgery were reviewed. Presentation symptoms were analyzed as possible predictors. Timing of intestinal adenocarcinoma occurrence in patients with CD was analyzed including all the 347 consecutive patients that had undergone surgery for CD in our institute from January 1984 to June 2008. Life table analysis and uni/multivariate analyses were performed. ResultsTen men and two women underwent surgery for intestinal cancer in CD with a median age of 50 years (31–68). Carcinomas were localized in the terminal ileum in four cases, right colon in three, transverse colon in one, sigmoid colon in one, rectum in two, and an anorectal fistula in one. Only three patients were pre-operatively diagnosed with cancer. At multivariate analysis only age (OR 1.057 (95% CI 0.999–1.107), p = 0.05) and obstruction (OR 6.530 (95% CI 1.533–27.806), p = 0.01) significantly predicted cancer diagnosis. The risk rate (RR) for cancer occurrence started to rise at the end of the third decade of life (RR = 0.005). The analysis of risk rate for cancer occurrence during overt CD showed that it is initially high at onset (RR = 0.001) and after two other peaks at 150 months from onset, it began to rise again. The presence of Crohn’s colitis was associated to a significant risk of cancer (HR = 4.790, p = 0.009) while the use of 5-ASA resulted to be a protective factor against cancer occurrence (HR = 0.122, p = 0.013). DiscussionIn CD, rectal bleeding, the most common alarm symptom for intestinal cancer, is not useful for an early diagnosis. CD patients presenting with an older age and obstruction should be thoroughly investigated to rule out neoplastic lesions. There is probably no safe interval of CD where surveillance for intestinal cancer can be omitted. In the meantime, even in absence of active disease, all CD patients should undergo therapy with 5-ASA.

Optimizing use of 5-ASA in the treatment of ulcerative colitis: Focus on patient compliance and adherence

Ulcerative colitis is a chronic condition that requires long-term treatment. The first-line therapy remains 5-ASA, which is available in a variety of different formulations and dosing schedules. Multiple studies have demonstrated that adherence rates to prescribed 5-ASA products is below what would have been expected with significant consequences for important outcomes. Worse disease outcomes, higher medical costs, and even potentially higher rates of colorectal cancer have been associated with nonadherence. Nonadherence is multifactorial, fluid in nature over time, and dependent on disease activity level. Interventions to improve adherence rates have to be individualized. With the advent of simpler dosing regimens it was assumed that adherence rates would improve, but this has not necessarily been the case. Despite our current knowledge about nonadherence, it remains difficult to manage in the long term.

255 Aminosalicylates, Thiopurines and the Risk of Colorectal Cancer in Inflammatory Bowel Diseases: A Case-Control Study Nested in the CESAME Cohort

7-3589). There was no impact of years of 5ASA use on outcomes. Conclusion In study I we could not find evidence that 1 or 5 years of consecutive 5-ASA use was chemoprophylactic in IBD (in fact it tended to increase the risk). We could not discount that longer use might have been chemoprophylactic. In Study II with a longer duration of follow up and more CRC cases we could not discern that 5-ASA was chemoprophylactic. Overall, our results support the majority of studies to date that 5-ASA is not chemoprophylactic in IBD for CRC.

Oral 5-aminosalicylates for prevention of postoperative relapses in crohn's disease

<h3>Background</h3> The use of 5-aminosalicylates (5-ASAs) in Crohn9s disease (CD) is controversial. A recent Cochrane review found that 5-ASAs are not effective for the maintenance of medically-induced remission in CD but their role in the maintenance of surgically-induced remission is unclear. <h3>Aim</h3> To evaluate articles that investigated the use of 5-ASAs for prevention of postoperative relapses in CD. <h3>Design</h3> Systematic review and meta-analyses of randomised controlled trials (RCTs) published between 1966 and October 2009. <h3>Methods</h3> Data sources were MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Inflammatory Bowel Disease Specialised Register and reference lists of retrieved articles. The authors included trials which compared oral 5-ASAs with either placebo or other interventions. Data extraction and assessment of methodological quality were performed independently by two reviewers. <h3>Results</h3> Ten RCTs met the inclusion criteria. Meta-analysis of the results of 8 placebo-controlled trials involving 1061 participants showed that the risk of postoperative clinical relapses was significantly reduced in patients who received oral 5-ASA compared with those who received placebo (pooled odds ratio 0.68, 95% CI 0.52 to 0.90). The incidence of adverse events was not statistically significantly different between the 5-ASA and placebo groups (pooled odds ratio 1.02, 95% CI 0.60 to 1.76). In two other studies in which oral 5-ASAs were compared with azathioprine, no statistically significant difference in clinical relapses was found but the sample sizes of these studies were small. <h3>Conclusion</h3> Oral 5-ASAs are superior to placebo for the prevention of postoperative relapses in Crohn9s disease. The authors recommend the use of 5-ASAs as maintenance therapy following surgically-induced remission in CD as they appear effective and are not associated with significant adverse events.

PWE-024 Practical outcomes of thiopurine metabolite measurement in a tertiary paediatric gastroenterology and hepatology service

Introduction Clinical response to thiopurines is dependent on the concentration of its active metabolite, 6-thioguanine nucleotide (6-TGN).1 Dosing is, however, unpredictable because the concentration of 6-TGN is dependent on thiopurine methyl transferase (TPMT) activity, an enzyme with common genetic polymorphisms. Because metabolite monitoring is not commonplace in the UK, some clinicians use proxy measures to assess response to thiopurines. We aim to evaluate how measuring thioguanine metabolites measurement influences clinical practice. Methods Thiopurine metabolites were measured in children who had been on medication for 3 months or more. For each measurement, data were collected on dosage, disease severity, concomitant use of 5-ASA, haematological and biochemical indices, and changes to management. Therapeutic 6-TGN levels were defined as 235–400 pmol/8×108 RBCs. Toxicity is defined as WBC 2× elevated. Result 64 individuals studied, median age 14 years. Underlying diagnoses were “IBD” (54/64) and “other” (10/64). 59 treated with AZA, 5 with 6-MP. 95 separate measurements were made. TPMT phenotype was measured in 51/64 patients,40/51 had “normal” phenotype, and 11/51 had heterozygous TPMT mutations. Initial 6-TGN levels were higher in heterozygotes (median levels 836 vs 328, p=0.001) at comparable doses of thiopurine (median 1.9 vs 2.2 mg/kg, p=0.11). On first measurement, only 30% patients had 6-TGN levels within therapeutic levels. 30% were subtherapeutic and 40% were supra-therapeutic. 9% had 6-TGN levels >800. Toxicity occurred in 8 cases (9%). Leucopaenia (WBC Conclusion Based on standard dosing regimens, clinicians can expect to achieve therapeutic levels of 6-TGN in a minority of cases. Measuring Thiopurine metabolites aids therapeutic dose alteration, detects potential toxicity, and identifies issues of non-compliance that cannot be detected on routine blood monitoring.

In-Source Decay and Fragmentation Characteristics of Peptides Using 5-Aminosalicylic Acid as a Matrix in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry

The use of 5-aminosalicylic acid (5-ASA) as a new matrix for in-source decay (ISD) of peptides including mono- and di-phosphorylated peptides in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) is described. The use of 5-ASA in MALDI-ISD has been evaluated from several standpoints: hydrogen-donating ability, the outstanding sharpness of molecular and fragment ion peaks, and the presence of interference peaks such as metastable peaks and multiply charged ions. The hydrogen-donating ability of several matrices such as alpha-cyano-4-hydroxycinnamic acid (CHCA), 2,5-dihydroxybenzoic acid (2,5-DHB), 1,5-diaminonaphthalene (1,5-DAN), sinapinic acid (SA), and 5-ASA was evaluated by using the peak abundance of a reduction product [M + 2H + H](+) to that of non-reduced protonated molecule [M + H](+) of the cyclic peptide vasopressin which contains a disulfide bond (S-S). The order of hydrogen-donating ability was 1,5-DAN > 5-ASA > 2,5-DHB > SA = CHCA. The chemicals 1,5-DAN and 5-ASA in particular can be classified as reductive matrices. 5-ASA gave peaks with higher sharpness for protonated molecules and fragment ions than other matrices and did not give any interference peaks such as multiply-protonated ions and metastable ions in the ISD mass spectra of the peptides used. Particularly, 1,5-DAN and 5-ASA gave very little metastable peaks. This indicates that 1,5-DAN and 5-ASA are more "cool" than other matrices. The 1,5-DAN and 5-ASA can therefore be termed "reductive cool" matrix. Further, it was confirmed that ISD phenomena such as N-Calpha bond cleavage and reduction of S-S bond is a single event in the ion source. The characteristic fragmentations, which form a- and (a + 2)-series ions, [M + H - 15](+), [M + H - 28](+), and [M + H - 44](+) ions in the MALDI-ISD are described.

Ocular manifestations in a community-based cohort of patients with inflammatory bowel disease

Ophthalmologic diseases in patients with inflammatory bowel disease (IBD) have been reported with varying frequency, mostly from tertiary referral centers. The aim was to describe the spectrum of ophthalmologic conditions in patients with IBD in a community setting and to compare it with a control non-IBD cohort. A prospective cohort of patients with Crohn's disease (CD), ulcerative colitis (UC), and non-IBD controls underwent evaluation by an ophthalmologist, including visual acuity, slit-lamp exam, and assessment of lacrimal output. The ophthalmologic exam was completed in 112 subjects; 48 with CD, 40 with UC, and 24 controls. Active intestinal disease was present in 52/88 (59%) of the IBD patients, and 79/88 (89%) were taking 5-aminosalicylates (5-ASAs). The IBD and control populations had similar age and gender profiles. Patients with IBD were more likely to report ocular symptoms (odds ratio [OR] 5.6, 95% confidence interval [CI] 1.5-20), particularly dry eyes (OR 5.3, 95% CI 1.4-19), than the control population. On objective exam, 42% of IBD patients had evidence of dry eyes. In a univariate analysis, 5-ASA use was associated with an increased risk of ocular symptoms (OR 7.4, 95% CI 0.9-64), and 5-ASA use >3 g per day was associated with an increased odds ratio of dry eyes (OR 15, 95% CI 1.9-122). Active disease was not associated with eye symptoms or dry eyes. Other eye conditions such as episcleritis, uveitis, or cataracts were infrequent in this cohort. Patients with IBD in the community frequently have dry eyes. This is associated with 5-ASA use, particularly doses >3 g per day. Whether this is a surrogate marker of disease severity is unclear.

Describing Characteristics and Chronology of Ulcerative Colitis in African Americans

To describe patient and disease characteristics, treatment response and outcome in African Americans (AA) with ulcerative colitis (UC). Single-center, retrospective study. We reviewed records of 50 AA patients with an established diagnosis of UC seen at the outpatient clinic between 2000 and 2009. Demographic and clinical variables were examined using descriptive statistics. The mean age at diagnosis was 37 years (range of 12-69 years). At the end of observation, mean duration of disease was 11 years and mean patient age was 47 years. Men and women were equally represented. The mean body mass index (BMI) was 28 mg/kg2. Twenty nine (73%) patients were overweight or obese. At diagnosis, 24 (48%) patients had pancolitis, 15 (30%) had left sided disease and 11 (22%) had proctitis/proctosigmoiditis. Nineteen (38%) patients had extra-intestinal manifestations which were predominantly rheumatologic (84%). Eight (20%) and 4 (10%) patients had family history of inflammatory bowel disease (IBD) and colorectal cancer respectively. Twenty three (46%) patients had a past history of 5-ASA agent use and 34 (68%) were on a 5-ASA agent at last observation. The most common reason for discontinuation of a 5-ASA agent was lack of response. Mesalamine Delayed-Release was overall the most common5-ASA agent used and 16 (57%) of the patients using a 5-ASA agent were on it at last observation. The second most common 5-ASA agent being used was sulfasalazine. Twelve (24%) patients had a past history of azathioprine/6-mercaptopurine (AZA/6-MP) use whereas six (12%) were on AZA/6-MP at last observation. Four (8%) patients had a past history of biologic use that included adalimumabor infliximab. Five (10%) patients were on a biologic at last observation. The two most common reasons for discontinuation of both AZA/6-MP and biologics were lack of response and intolerance. Seventeen (34%) patients had a significant history of steroid use with the mean duration of steroid use per year of 60 days. Eight (16%) patients had undergone total colectomy with ileal J pouch-anal anastomosis. The mean duration to surgery in these patients was 8 years. Calculation of average clinical disease activity during last year of observation revealed that 23 (46%) patients were in clinical remission, 15 (30%) had mild disease whereas 12 (24%) had moderate to severe disease. The corresponding last outpatient endoscopic evaluation revealed that 16 (36%) patients' disease was inactive, 14(32%) had mild mucosal disease whereas 14 (32%) patients had moderate to severe mucosal disease. None of the patients were found to have dysplasia and none died. Our study generally agrees with findings of previous studies done on AA patients with UC. These include a relatively low rate of steroid, traditional immune modulator and biologic use as well as a low rate of surgical intervention, with the rate of 5-ASA agent use being high. Notable difference includes an older age at diagnosis of UC in our cohort. At a given time, approximately 75% AA patients with UC are either in clinical remission or have mild clinical disease and 66% have inactive or mild mucosal disease.

Description and comparison of Crohnʼs Disease and Ulcerative Colitis in African Americans

To compare patient characteristics, treatment response and outcome in African Americans (AA) with Crohn's disease (CD) and ulcerative colitis (UC). Single-center, retrospective study comparing 99 CD and 50 UC AA patients. Categorical variables in each group were compared using chi-square or Fisher's exact test. Continuous variables were compared using the two-group Wilcoxan rank-sum test. The level of significance was assessed at p < 0.05. Women comprised 74% of the CD cohort whereas there was equal gender distribution in the UC cohort (p= 0.0039). AA patients with CD had higher rate of surgery compared to UC patients with 61% of CD patients undergoing surgery vs.16% of UC patients (p<0.0001). Time to first surgery was shorter in CD than in UC (p= 0.0199). Traditional immune modulators or biological agents were used more often for CD patients than for UC patients. Thirty percent of CD patients had been on a biologic in the past compared to 8% of UC patients (p= 0.0022). At last observation, 36% of CD patients were being treated with a biological agent compared to 10% of those with UC (p= 0.0007). Adalimumab was used more commonly to treat CD patients whereas infliximab was used more commonly for UC patients. Thiopurine analogues were employed in treatment of CD patients more frequently than in the treatment of UC patients with 28% of CD vs.12% or UC patients on a thiopurine analogue (p= 0.0253). 5-ASA agents were used more commonly for treatment of UC patients with 68% of UC vs. 28% of CD patients on a 5-ASA agent (p<0.0001). Mesalamine Delayed-Release was the most common 5-ASA agent used to treat both CD and UC patients followed by sulfasalazine. Mesalamine was used in CD patients but none of the UC patients were on it. Lack of response and intolerance were the two most common reasons for discontinuation of immune modulators in both groups. Family history of inflammatory bowel disease (IBD) was more common in UC patients (20%) than in CD patients (14%) but this did not reach statistical significance. Twenty-two percent of UC patients had a family history of autoimmune disease vs. 8% of CD patients and it reached statistical significance (p= 0.0283). Ten percent patients from both groups had family history of colorectal cancer (CRC). Family history of cancer other than CRC was more common in UC (44%) than in CD (28%) and trended toward statistical significance (p= 0.0805). Steroid use and smoking were more common in CD without reaching statistical significance. Clinical and mucosal disease activity was higher in CD but did not reach statistical significance. Age at diagnosis, disease duration, age at last observation and BMI were greater in UC patients but they did not reach statistical significance. Notable differences between CD and UC in AA patients include differences in gender distribution, degree of genetic link to autoimmune conditions, 5-ASA agent use, immune modulator and biologic requirement including the actual biologic employed in treatment and the need for surgical intervention. CD follows a slightly more intensive course in terms of disease activity.

Small bowel resection rates in Crohnʼs disease and the indication for surgery over time: Experience from a large tertiary care center

Our primary aim was to determine if the rate of small bowel resection (SBR) has declined over time among Crohn's disease (CD) patients seen at a single academic institution. A secondary aim was to establish whether the indication for surgery has changed. Patients with a primary or secondary ICD-9 code for CD (555.0-555.9) who underwent SBR at the University of Pittsburgh were included. Patients were divided into 4 separate time periods based on when they had surgery: 1995-1998 (Period 1), 1999-2001 (Period 2), 2002-2004 (Period 3), and 2005-2007 (Period 4). Medical records were reviewed for the 6 months preceding surgery. Use of 5-ASAs, immunomodulators (IMs), tumor necrosis factor (TNF) antagonists, and corticosteroids were noted. Disease behavior was defined as nonstricturing, nonpenetrating (B1), stricturing (B2), and penetrating (B3). Proportions of patients undergoing SBR were calculated according to calendar cohort and these rates were examined for time trends. In all, 227 unique patients were analyzed for a total of 236 surgeries. The rates of 5-ASA, IM, and corticosteroid use were similar across the 4 time periods. By contrast, TNF antagonist usage progressively increased over time (0%, 18%, 34%, 35%; P = 0.0002). The annual rate of SBR per period did not change (1.6%, 1.9%, 1.6%, 1.9%; P = 0.93). Similarly, the disease behavior did not change over time. While the frequency of TNF antagonist use in CD at the University of Pittsburgh has increased over time, the rate of SBR and indication for surgery has remained unchanged. These findings may be explained by long-standing, complicated disease refractory to medical therapy.

Azathioprine maintains long-term steroid-free remission through 3 years in patients with steroid-dependent ulcerative colitis†

Studies assessing the efficacy of azathioprine (AZA) in steroid-dependent ulcerative colitis (SD-UC) are scarce. The purpose of this trial was to explore the efficacy of AZA in maintaining steroid-free remission in SD-UC patients and the factors associated with sustained response. In this observational cohort study, 42 subjects with SD-UC were recruited for AZA therapy during a 3-year period. AZA was adjusted for a target dose of 2-3 mg/kg/day. Steroid therapy was tapered off following a standardized regimen. The primary endpoint was the annual rate of steroid-free response to AZA. Secondary endpoints included clinical recurrence, yearly steroid dose, and safety of treatment. On an intention-to-treat basis, the proportion of patients remaining in steroid-free remission at 12, 24, and 36 months was 0.55, 0.52, and 0.45, respectively. A significant decrease in the flare-ups rate and in requirement for steroids were observed during 3 years on AZA compared with the previous year (P = 0.000 for both). Patients with and without sustained response were comparable according to demographics, extent of disease, dose of AZA, steroids, and 5-aminosalicylate (5-ASA) use. Only disease duration <36 months was associated with off-steroids remission (P = 0.02, odds ratio [OR] 3.12, 95% confidence interval [CI] 1.89-7.64). The AZA benefit-risk profile was favorable. In this open-label observational trial AZA showed sustained efficacy for maintenance of clinical remission off steroids and steroid sparing through 3 years of therapy in SD-UC. Patients with earlier UC are those who most probably will have sustained steroid-free remission at the end of 12 months while on AZA.

Predictors of persistence with 5‐aminosalicylic acid therapy for ulcerative colitis

Individuals with ulcerative colitis (UC) are at risk for poor persistence with therapy. To identify factors predicting persistence with 5-aminosalicylic acid (5-ASA) therapy after 3 and 12 months in subjects with UC. In this retrospective cohort study, persistence with 5-ASA therapy was determined from prescription refill data from a commercial health insurance claims database. The analysis included subjects with UC who filled a prescription for any oral 5-ASA between October 2002 and September 2004. Persistence was defined as prescription refill at 3 and/or 12 months. Multivariate logistic regression modelling identified variables independently associated with persistence at 3 and 12 months. In all, 3574 subjects were identified. Fifty-seven per cent (2044) were persistent at 3 months. Glucocorticoid use before the index prescription predicted improved persistence at 3 months. Psychiatric diagnosis, mail order of the index prescription, female gender and co-pay predicted decreased persistence. At 12 months, 1124 (55%) remained persistent. Rectal 5-ASA use, older age and switching to a different 5-ASA predicted improved persistence at 12 months. Hospitalization for a gastrointestinal condition, mail order of the 3-month prescription and number of co-morbid illnesses predicted lower persistence. Persistence with 5-ASA treatment in UC is complex and multifactorial, and differs by time period.

W1236 Safety of Chronic 5-ASA Use in the Elderly Inflammatory Bowel Disease Population

W1236 Safety of Chronic 5-ASA Use in the Elderly Inflammatory Bowel Disease Population

S1243 Practice Patterns of 5-ASA Use in Ulcerative Colitis (UC): Results of a National Vignette Survey Comparing Experts vs. Community Providers

S1243 Practice Patterns of 5-ASA Use in Ulcerative Colitis (UC): Results of a National Vignette Survey Comparing Experts vs. Community Providers

Live Typhoid Vaccine for IBD-Patients–-Well Tolerated and with Possible Therapeutic Effect

Background: Our incidental observation of a remarkable improvement of disease activity following vaccination against typhoid in a patient with inflammatory bowel disease (IBD) was the incentive of this pilot study. Methods: Ten IBD-patients (7 with ulcerative colitis and 3 with Crohn’s disease) with disease activity grade 2–10 on simple colitis index were included in the study. The use of 5-ASA and prednisolone ≥12.5 mg/day, but no other immunosuppressive drugs, were allowed during the trial. Live typhoid vaccine containing Salmonella serovar Ty21a (Vivotif ®, Berna) was given in standard doses on day 1, 3 and 5. Symptoms and endoscopic findings were followed up for a 3-months-period. Results: Improvement of abdominal symptoms was recorded in 8 patients after 90 days, one patient was unchanged and one slightly worse. Endoscopic findings improved in 4 patients and were unchanged in 5 patients after 90 days. No side effects were observed. Conclusion: Our results indicate that a live typhoid vaccine is well tolerated by patients with IBD of moderate activity. The symptomatic and endoscopic improvements were not dramatic, but encouraging enough to warrant further studies on the potential therapeutic effect of live typhoid vaccine on patients with IBD.

Crohnʼs Disease-Associated Colonic Dyplasia &amp; Cancer: Lessons Learned from 93 Cases

Purpose: Endoscopic surveillance is not always employed for patients with colonic Crohn's disease (CD). In addition, management of CD-associated colonic dysplasia or cancer, once detected, is debatable. The aims of the study were to characterize clinical, endoscopic, and histologic features & natural history of CD-associated dysplasia/cancer as a source of information for 1) surveillance recommendations; 2) risk factors for progression from dysplasia to cancer; & 3) surgical treatment. Methods: Database search was performed for patients with CD-associated dysplasia/cancer during the last 30 years. Biopsies and surgical specimens were reviewed by an expert GI pathologist. Demographic, clinical, endoscopic and surgical variables were studied. Results: 93 patients with CD-associated dysplasia/cancer were identified: 32 (34%) had dysplasia, 22 (24%) had dysplasia and cancer and 39 (42%) had cancer without dysplasia. High-grade dysplasia (HGD) was found in 49/93 (53%) [72% of the dysplasia group and 43% of the cancer group] and was multifocal in 27/49 (55%) [57% in dysplasia group, and 54% in cancer group]. Low-grade dysplasia (LGD) was found in 29/93 (31%) [59% in dysplasia group, and 16.4% in cancer group] and was multifocal in 13/29 (45%) [47% in dysplasia group, and 40% in cancer group]. 18/61(30%) of cancer patients had dysplasia found in at least 1 preoperative endoscopy. CD characteristics are shown in Table 1. Patients with dysplasia who were treated with 5-aminosalicilates (5ASA) at any time, were less likely to progress to cancer (OR 2.94, 95% CI 1.22–7.12 P= 0.016) than those without 5ASA treatment. Conclusion: 1) Dysplasia in colonic CD often is multifocal; 2) Concurrent dysplasia was found in a substantial number of CD-associated colon cancers; and 3) 5ASA use may protect from progression of dysplasia to cancer. Our findings support routine endoscopic surveillance for colonic CD as in ulcerative colitis and chemoprevention with 5ASA. Colonic CD with dysplasia may require radical surgery due to the multifocal nature of dysplasia and the risk for future cancer.Table: Risk Factors for Dysplasia Progression to Cancer