Ulcerative Colitis: Kane SV

Kane SV. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA. · Drugs. · Pubmed #19093702 No free full text.

Abstract: This review examines studies of patient adherence to 5-aminosalicylic acid therapy conducted outside the context of a controlled therapy trial, considers the reasons why patients do not adhere to their medication and its consequences, and interventions to improve adherence and disease outcomes. Non-adherence in the inflammatory bowel disease population tends to mirror other chronic illnesses, in the range of 40-60%. Factors that appear to affect adherence include younger age, single status, heavy pill burden, perception of lack of benefit and feeling uninformed about the effect of medication. Three important outcomes of non-adherence include increased risk for disease activity, increased healthcare costs and the possible increased risk of dysplasia/colorectal cancer. Strategies to improve adherence include patient education and 'health literacy', along with discussing patient misperceptions and fears on an individual basis, decreasing the daily regimen and switching to high-dose formulations, and incorporating patient self-management techniques into practice.

Zisman TL, Kane SV. · Clinical Research Fellow in Gastroenterology, The University of Chicago Hospitals, 5841 S. Maryland Avenue MC 4076, Chicago, IL 60637, USA. · Expert Rev Gastroenterol Hepatol. · Pubmed #19072438 No free full text.

Abstract: The introduction of biologic agents to the therapeutic arsenal has dramatically impacted the way we treat patients with inflammatory bowel disease, allowing clinicians to achieve lasting remission in patients who are unresponsive to conventional therapies. New research continues to expand our understanding of the inflammatory cascade of ulcerative colitis and Crohn's disease, revealing a host of potential therapeutic targets for intervention. As we look toward the future in this rapidly developing field, we must learn how best to incorporate these new agents into the treatment algorithm to enhance or replace conventional therapies.

Higgins PD, Rubin DT, Kaulback K, Schoenfield PS, Kane SV. · Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA. · Aliment Pharmacol Ther. · Pubmed #18945258 No free full text.

Abstract: BACKGROUND: Ulcerative colitis (UC) can be maintained in remission with 5-aminosalicylic acid (5-ASA) medications, but frequent non-adherence by patients who are feeling well has been associated with more frequent flares of colitis. AIM: To perform a systematic review of the published literature and unpublished randomized clinical trials (RCTs) regarding the impact of non-adherence with 5-ASA medications on the incidence of UC flares and costs of care. METHODS: A search of MEDLINE, EMBASE and the Cochrane databases was performed. Prospective studies of UC maintenance with 5-ASAs in adults were selected if they included data on adherence and disease flares. Studies using insurance claims data to estimate the impact of non-adherence on cost of care were included. Data from unpublished RCTs were obtained from the FDA with a request under the Freedom of Information Act. RESULTS: The relative risk for flare in non-adherent vs. adherent patients ranged from 3.65 to infinity. Data were obtained from six unpublished 5-ASA RCTs, but none measured the impact of adherence on disease activity. The comorbidity-adjusted annual costs of care in adherent patients were 12.5% less than in non-adherent patients, despite increased medication expenditures. CONCLUSIONS: A substantial proportion of UC flares and medical costs of UC are attributable to 5-ASA non-adherence. As non-adherence to 5-ASA medications is common, cost-effective strategies to improve adherence are needed. The impact of adherence on disease activity should be measured in RCTs of all inflammatory bowel disease treatments.

Kane SV, Brixner D, Rubin DT, Sewitch MJ. · Mayo Clinic College of Medicine, Division of Gastroenterology and Hepatology, 200 First Street, Sw, 19th Floor, Rochester, MN 55905, USA. · J Manag Care Pharm. · Pubmed #18240888 links to  free full text

Abstract: BACKGROUND: Non-adherence to therapy is a widespread problem, with typical adherence rates for prescribed medications being approximately 50%. An estimated 20% to 50% of patients with ulcerative colitis (UC) do not take their medications as prescribed, resulting in higher disease-recurrence rates and potentially higher health care costs. OBJECTIVE: To characterize the problem of non-adherence in UC, to review the many factors affecting compliance and persistence in this population, and to discuss practical strategies to improve adherence in these patients. SUMMARY: Adherence to and persistence with medication are complex and multifactorial behaviors. Factors shown to affect adherence in UC patients include disease extent and duration, cost of medications, fear of adverse effects, individual psychosocial variables, and the patient-physician relationship. In contrast, recent data do not support an important role for treatment-related factors such as daily dose, regimen, and formulation in influencing adherence in this population, particularly with longer duration of use. Strategies to improve adherence should involve the patient, the provider, and the health care delivery system. For UC patients, knowledge and discussion of the rationale for supporting persistence, such as recent data regarding agents that have a potential chemoprotective benefit, may encourage persistence, even during periods of quiescence. The patient-physician relationship is critical in encouraging adherence, particularly with respect to education, open communication, and agreement regarding the value of the assigned treatment. Health care delivery systems can improve adherence by encouraging the participation of multidisciplinary teams, providing reporting and tracking systems, and eliminating financial barriers where possible.

Kane SV. · Section of Gastroenterology, Department of Medicine, The University of Chicago, Chicago, IL, USA. · Aliment Pharmacol Ther. · Pubmed #16480396 No free full text.

Abstract: Ulcerative colitis is a chronic inflammatory and debilitating disease requiring lifelong treatment. First-line therapy for ulcerative colitis is 5-aminosalicylic acid, which suffers from poor patient adherence outside the clinical trial setting. Formulations to deliver 5-aminosalicylic acid to the disease activity site, both orally and topically, are often inconvenient and require multiple daily dosing. Such regimens can interfere with normal life and reduce the overall quality of life, negatively impacting on treatment adherence and leading to poorer long-term outcomes. These include increased morbidity with an elevated risk of symptomatic relapse, possible greater risk of colorectal cancer and higher overall costs of care. Ulcerative colitis patients cite treatment regimen complexity, tablet quantity and dose frequency as key negative influencers of adherence. Solutions to these issues include addressing patient concerns, simplifying daily regimens and utilizing new formulations such as micropellet and multimatrix oral formulations, rectal gel and once-daily suppository formulations. This review examines the prevalence and impact of non-adherence to 5-aminosalicylic acid therapy among patients with ulcerative colitis, as well as drug delivery strategies that may enhance dosing regimens to improve patient acceptability, adherence and long-term clinical outcomes. It is a combination of understanding patient behaviour, recognizing signs of non-adherent behaviour and utilizing management strategies to change behaviour that will improve patient outcomes.

Loftus EV, Kane SV, Bjorkman D. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA. · Aliment Pharmacol Ther. · Pubmed #14723609 links to  free full text

Abstract: AIM: To determine whether there is a difference in short-term adverse events in patients with ulcerative colitis treated with mesalazine, olsalazine or balsalazide. METHODS: MEDLINE was searched for articles published until 2002. Randomized trials of oral mesalazine, olsalazine or balsalazide for the treatment of active disease or the maintenance of remission were included. Outcomes of interest were the frequencies of patients experiencing adverse events and those withdrawn due to adverse events. RESULTS: Forty-six trials were included. One study of mesalazine vs. sulfasalazine for active colitis showed significantly fewer patients with adverse events with mesalazine. Both balsalazide vs. sulfasalazine studies for active disease showed significantly fewer withdrawals with balsalazide. One trial of balsalazide vs. sulfasalazine for maintenance showed significantly fewer patients with adverse events with balsalazide. Otherwise, no significant differences in safety outcomes were noted. CONCLUSION: All three 5-aminosalicylic acid agents are safe in the short term. In mesalazine-treated patients, the frequencies of adverse events or withdrawals due to adverse events were comparable with those in placebo-treated patients and lower than those in sulfasalazine-treated patients. Overall, adverse events or withdrawals were not significantly more frequent with olsalazine than with placebo or sulfasalazine. Adverse events and study withdrawals on balsalazide were less frequent than those on sulfasalazine.

Kane SV, Bjorkman DJ. · University of Chicago, Chicago, Illinois, USA. · Rev Gastroenterol Disord. · Pubmed #14668693 No free full text.

Abstract: The authors set out to critically review the current data on the efficacy of oral 5-aminosalicylic acid (5-ASA) agents for active ulcerative colitis (UC). Thirty-one studies were identified; 19 met entry criteria. Three trials with mesalamine showed statistical significance versus placebo; those with olsalazine or balsalazide did not. No agent was statistically different from sulfasalazine. In 2 of 3 trials of balsalazide versus mesalamine, results for defined primary and secondary endpoints failed to demonstrate statistically significant differences. Studies suggest that mesalamine is superior to placebo for treating active UC. Five-ASA products appear to be as effective as sulfasalazine, but available data do not suggest a difference in efficacy between any of the 5-ASA preparations.

Tuvlin JA, Kane SV. · Department of Medicine, Division of Gastroenterology, University of Chicago, 5841 South Maryland Ave, MC 4076, Chicago, IL 60637, USA. · Expert Opin Investig Drugs. · Pubmed #12605569 No free full text.

Abstract: Ulcerative colitis is a chronic inflammatory disease of the colon of unknown cause. Its course is one of relapse and remission and requires therapy for both the induction and maintenance of remission. Progress in the fields of genetics and immunology affords important advances in our understanding of the inflammatory process. Traditional therapy for ulcerative colitis with nonspecific anti-inflammatories remains our gold standard. This review examines the most recent compounds in development for the treatment of ulcerative colitis, including data from early clinical trials and the potential clinical impact of future entities.

Kane SV. · Department of Medicine, Division of Gastroenterology, University of Chicago, 5841 South Maryland Ave, MC 4076, Chicago IL 60637, USA. · Expert Opin Investig Drugs. · Pubmed #11772246 No free full text.

Abstract: Ulcerative colitis is a chronic inflammatory disease of unknown cause. Its course is one of relapse and remission and requires therapy for both the induction and maintenance of remission. The progress in the fields of genetics and immunology has afforded important advances in our understanding of the inflammatory process. Traditional therapy with non-specific anti-inflammatories for ulcerative colitis remains our gold standard as newer targeted therapies have failed to provide any improved efficacy. This review examines the most recent compounds in development for the treatment of ulcerative colitis, including data from early clinical trials and the potential clinical impact of future entities.

Kane SV, Accortt NA, Magowan S, Brixner D. · Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA. · Aliment Pharmacol Ther. · Pubmed #19183154 No free full text.

Abstract: BACKGROUND: Individuals with ulcerative colitis (UC) are at risk for poor persistence with therapy. AIM: To identify factors predicting persistence with 5-aminosalicylic acid (5-ASA) therapy after 3 and 12 months in subjects with UC. METHODS: 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. RESULTS: 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. CONCLUSION: Persistence with 5-ASA treatment in UC is complex and multifactorial, and differs by time period.

Rubin DT, Siegel CA, Kane SV, Binion DG, Panaccione R, Dubinsky MC, Loftus EV, Hopper J. · Section of Gastroenterology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois, USA. · Inflamm Bowel Dis. · Pubmed #19067414 No free full text.

Abstract: BACKGROUND: Two national internet surveys were conducted to understand how patients perceive the impact of ulcerative colitis (UC) relative to gastroenterologists. METHODS: In total, 451 patients with UC (20% mild, 63% moderate, 13% severe, 4% unsure [patient self-assessment]) were recruited for one survey and 300 gastroenterologists (not associated with the patients) were recruited for the other survey. RESULTS: Patients reported, on average, 8 (self-defined) flares per year; this was more than the number anticipated by gastroenterologists. Sixty-two percent of patients with UC reported that their disease made it difficult to lead a normal life, compared with gastroenterologists' estimations of 36%. Only 42% of patients believed that being in remission could mean living without symptoms. Both patients and gastroenterologists reported that it is difficult for patients to take medication as prescribed every day (42% and 90%) and that managing UC medication is a struggle for patients (49% and 41%). Forty-six percent of patients admitted nonadherence to their therapy over the previous week, while gastroenterologists believed that 41% of their patients were not adherent. CONCLUSIONS: These surveys identified disparities between patients' and gastroenterologists' perceptions of the impact of UC on patients' lives. The results suggest that more patients than gastroenterologists estimated chose to adapt their lives to accommodate UC rather than act to optimize therapy and adherence. Improved communication between patients and gastroenterologists, as well as better management strategies and education are necessary.

Yen EF, Kane SV, Ladabaum U. · Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California 94143-0538, USA. · Am J Gastroenterol. · Pubmed #18775007 No free full text.

Abstract: OBJECTIVES: Oral 5-aminosalicylic acid (5-ASA, mesalamine) is effective in inducing and maintaining remission in ulcerative colitis (UC). The relative benefits and costs of maintenance 5-ASA therapy are uncertain. Our aims were to evaluate this strategy's potential cost-effectiveness. METHODS: We constructed a Markov model to compare two strategies over 2 yr: (a) no maintenance 5-ASA, with 5-ASA 4.8 g/day given for flares, (b) maintenance 5-ASA 2.4 g/day, escalated and maintained at 4.8 g/day after the first flare. In both arms, the failure to induce remission led to other treatments, as needed: prednisone, parenteral corticosteroids, cyclosporine, 6-mercaptopurine, infliximab, and colectomy. RESULTS: Without maintenance 5-ASA, the mean flares per person were 1.92, and the mean cost per person was $3,402. With maintenance 5-ASA providing a relative risk of flare of 0.7 at 5-ASA cost of $198/month, flares per person decreased to 1.38 at a cost of $8,810/flare prevented. Maintenance 5-ASA increased discounted quality-adjusted life-years per person (QALYs per person) from 1.75 to 1.77 at a discounted cost of $224,000/QALY gained. The results were most sensitive to the flare risk reduction and cost of 5-ASA, the utilities of being in remission without or with 5-ASA, and the colectomy rates. At $15/month (the cost of sulfasalazine), maintenance 5-ASA cost $640/flare prevented and $16,300/QALY gained. CONCLUSION: Maintenance 5-ASA therapy decreases UC flares, but its cost may be substantial, depending on society's willingness to pay. If sulfasalazine can be tolerated and yields comparable benefits, sulfasalazine maintenance therapy is likely to be cost-effective. The cost per QALY gained by 5-ASA maintenance is highly dependent on the quality of life while taking versus not taking maintenance 5-ASA, highlighting the importance of patients' preferences.

Reddy D, Murphy SJ, Kane SV, Present DH, Kornbluth AA. · Division of Gastroenterology, Mount Sinai Medical Center, One Gustave Levy Place, New York, New York, USA. · Am J Gastroenterol. · Pubmed #18422816 No free full text.

Abstract: BACKGROUND: There are few studies that describe the medical treatment and colitis response rates among patients with a severe relapse of inflammatory bowel disease (IBD) during pregnancy, and few studies of the effect of such a relapse on birth outcomes in these patients. OBJECTIVES: To describe the treatment and response rates of severe colitis in pregnancy, and to assess the effects of a severe relapse of colitis during pregnancy on birth outcomes. METHODS: We performed a case control study of pregnant patients with IBD hospitalized for a disease relapse at two large treatment centers between 1989 and 2001. Details of management of disease relapse and maternal and fetal outcomes were recorded. RESULTS: Eighteen patients (11 ulcerative colitis, 6 Crohn's disease, 1 indeterminate colitis), mean age 28.6 yr (range 19-38) formed the study group; 41 age-matched pregnant IBD patients without disease relapse formed the control group. Study patients were hospitalized at a mean of 15.9-wk gestation (range 8-35) for a mean of 10.4 days (range 3-31). All 18 patients received IV hydrocortisone (mean dose 199 mg/day) and 7 patients (39%) either continued taking or were commenced on immunomodulators: IV cyclosporine (5 patients) and azathioprine/6-MP (3 patients). Fifteen patients (83%) had a clinical response to these medical treatments, 3 patients required colectomy. There were significant differences between study and control groups in gestation period (35.0 wk vs 38.7 wk, respectively, P= 0.0001) and birth weight (2,001 g vs 3,018 g, respectively, P < 0.0001). CONCLUSIONS: Treatment with IV hydrocortisone and IV cyclosporine appears effective at inducing remission of colitis but their use must continue to be confined to severely ill patients being treated at specialized centers. Severe relapses of colitis during pregnancy increase the risk of preterm birth and low birth weight.

Shugart YY, Silverberg MS, Duerr RH, Taylor KD, Wang MH, Zarfas K, Schumm LP, Bromfield G, Steinhart AH, Griffiths AM, Kane SV, Barmada MM, Rotter JI, Mei L, Bernstein CN, Bayless TM, Langelier D, Cohen A, Bitton A, Rioux JD, Cho JH, Brant SR. · Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21231, USA. · Genes Immun. · Pubmed #18246054 No free full text.

Abstract: Inflammatory bowel disease (IBD) is a complex genetic disorder of two major phenotypes, Crohn's disease (CD) and ulcerative colitis (UC), with increased risk in Ashkenazi Jews. Twelve genome-wide linkage screens have identified multiple loci, but these screens have been of modest size and have used low-density microsatellite markers. We, therefore, performed a high-density single-nucleotide polymorphism (SNP) genome-wide linkage study of 993 IBD multiply affected pedigrees (25% Jewish ancestry) that contained 1709 IBD-affected relative pairs, including 919 CD-CD pairs and 312 UC-UC pairs. We identified a significant novel CD locus on chromosome 13p13.3 (peak logarithm of the odds (LOD) score=3.98) in all pedigrees, significant linkage evidence on chromosomes 1p35.1 (peak LOD score=3.5) and 3q29 (peak LOD score=3.19) in Jewish CD pedigrees, and suggestive loci for Jewish IBD on chromosome 10q22 (peak LOD score=2.57) and Jewish UC on chromosome 2q24 (peak LOD score=2.69). Nominal or greater linkage evidence was present for most previously designated IBD loci (IBD1-9), notably, IBD1 for CD families at chromosome 16q12.1 (peak LOD score=4.86) and IBD6 in non-Jewish UC families at chromosome 19p12 (peak LOD score=2.67). This study demonstrates the ability of high information content adequately powered SNP genome-wide linkage studies to identify loci not observed in multiple microsatellite-based studies in smaller cohorts.

Kane SV, Reddy D. · Mayo Clinic, Rochester, Minnesota and University of Chicago, Chicago, Illinois, USA. · Am J Gastroenterol. · Pubmed #18177456 No free full text.

Abstract: BACKGROUND AND AIMS: The nature of inflammatory bowel disease (IBD) following menopause has not been previously studied. The aim of this study was to characterize the effect of menopause on disease activity and identify possible modifiers of disease activity. METHODS: This was a retrospective study of women followed at the University of Chicago IBD Clinic. Disease activity was assessed using clinical scoring systems during the pre- and postmenstrual periods of subjects. Variables of interest included: history of smoking, use of oral contraceptives (OCP) prior to onset of menopause, and use of hormone replacement therapy (HRT). RESULTS: Sixty-five women were included, 20 with ulcerative colitis and 45 with Crohn's disease. The median age of menopause was similar to historical controls. Twenty-three patients (35%) experienced active symptoms in the premenopausal time period and 25 patients (38%) had disease indices consistent with a flare within the first 2 yr after menopause (P > 0.05). There was no relation between those who had a pre- versus postmenstrual flare as a group (P > 0.05). However, there was a significant protective effect on disease activity with postmenopausal HRT use (hazard ratio [HR] 0.18, 95% confidence interval [CI] 0.04-0.72). There was also a dose-response effect noted with an HR with longer duration of use (0.20, 0.07-0.65). CONCLUSIONS: The likelihood of having a flare postmenopause is not different from having it premenopause. HRT, however, may provide a protective effect for disease activity in the postmenopausal period. The anti-inflammatory effects of estrogen may be the mechanism for this observation.

Dassopoulos T, Nguyen GC, Bitton A, Bromfield GP, Schumm LP, Wu Y, Elkadri A, Regueiro M, Siemanowski B, Torres EA, Gregory FJ, Kane SV, Harrell LE, Franchimont D, Achkar JP, Griffiths A, Brant SR, Rioux JD, Taylor KD, Duerr RH, Silverberg MS, Cho JH, Steinhart AH. · Johns Hopkins University Meyerhoff Inflammatory Bowel Disease Center, Baltimore MD, USA. · Inflamm Bowel Dis. · Pubmed #17427244 links to  free full text

Abstract: BACKGROUND: The NIDDK IBD Genetics Consortium (IBDGC) collects DNA and phenotypic data from inflammatory bowel disease (IBD) subjects to provide a resource for genetic studies. No previous studies have been performed on the reliability and validity of phenotypic determinations in either Crohn's disease (CD) or ulcerative colitis (UC) using primary records. Our aim was to determine the reliability and validity of these phenotypic assessments. METHODS: The de-identified records of 30 IBD patients were reviewed by 2 phenotypers per center using a standard protocol for phenotypic assessment. Each phenotyper evaluated 10 charts on 2 occasions 5 months apart. Reliability was expressed as the kappa (kappa) statistic. Performance characteristics were determined by comparison to a consensus-derived "gold standard" and by generation of receiver operating characteristic (ROC) curves. RESULTS: Agreement for diagnosis was excellent (kappa = 0.82; 95% confidence interval [CI]: 0.71-0.92). Agreement for CD location was good for jejunal, ileal, colorectal, and perianal disease with kappa between 0.60 and 0.74 but was fair for esophagogastroduodenal (kappa = 0.36). Agreement for UC extent (kappa = 0.67; 95% CI: 0.48-0.85), and CD behavior (kappa = 0.67; 95% CI: 0.49-0.83) were very good. Area under the ROC curves was greater than 0.84 for diagnosis, CD behavior, UC extent, and ileal and colonic CD location. CONCLUSIONS: IBD phenotype classification using a standard protocol exhibited very good to excellent inter- and intrarater agreement and validity. This study highlights the importance of standard protocols in generating reliable and valid phenotypic assessments. The data will facilitate estimates of phenotyping misclassification rates that should be considered when making inferences from IBD genotype-phenotype studies.

Silverberg MS, Duerr RH, Brant SR, Bromfield G, Datta LW, Jani N, Kane SV, Rotter JI, Philip Schumm L, Hillary Steinhart A, Taylor KD, Yang H, Cho JH, Rioux JD, Daly MJ, Anonymous00254. · Department of Medicine, Mount Sinai Hospital IBD Centre, University of Toronto, Toronto, Ontario, Canada. · Eur J Hum Genet. · Pubmed #17213842 links to  free full text

Abstract: Although the general association of the inflammatory bowel disease (IBD) 5 region on chromosome 5q31 to Crohn's disease (CD) has been replicated repeatedly, the identity of the precise causal variant within the region remains unknown. A recent report proposed polymorphisms in solute carrier family 22, member 4 (SLC22A4) organic cation transporter 1(OCTN1) and solute carrier family 22, member 5 (SLC22A5) (OCTN2) as responsible for the IBD5 association, but definitive, large-sample comparison of those polymorphisms with others known to be in strong linkage disequilibrium was not performed. We evaluated 1879 affected offspring and parents ascertained by a North American IBD Genetics Consortium for six IBD5 tag single nucleotide polymorphisms (SNPs) to evaluate association localization and ethnic and subphenotypic specificity. We confirm association to the IBD5 region (best SNP IGR2096a_1/rs12521868, P<0.0005) and show this association to be exclusive to the non-Jewish (NJ) population (P=0.00005) (risk allele undertransmitted in Ashkenazi Jews). Using Phase II HapMap data, we demonstrate that there are a set of polymorphisms, spanning genes from prolyl 4-hydroxylase (P4HA2) through interferon regulatory factor 1 (IRF1) with equivalent statistical evidence of association to the reported SLC22A4 variant and that each, by itself, could entirely explain the IBD5 association to CD. Additionally, the previously reported SLC22A5 SNP is rejected as the potential causal variant. No specificity of association was seen with respect to disease type and location, and a modest association to ulcerative colitis is also observed. We confirm the importance of IBD5 to CD susceptibility, demonstrate that the locus may play a role in NJ individuals only, and establish that IRF1, PDLIM, and P4HA2 may be equally as likely to contain the IBD5 causal variant as the OCTN genes.

Nguyen GC, Torres EA, Regueiro M, Bromfield G, Bitton A, Stempak J, Dassopoulos T, Schumm P, Gregory FJ, Griffiths AM, Hanauer SB, Hanson J, Harris ML, Kane SV, Orkwis HK, Lahaie R, Oliva-Hemker M, Pare P, Wild GE, Rioux JD, Yang H, Duerr RH, Cho JH, Steinhart AH, Brant SR, Silverberg MS. · Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Am J Gastroenterol. · Pubmed #16696785 No free full text.

Abstract: OBJECTIVES: Inflammatory bowel disease (IBD), comprising primarily of Crohn's disease (CD) and ulcerative colitis (UC), is increasingly prevalent in racial and ethnic minorities. This study was undertaken to characterize racial differences in disease phenotype in a predominantly adult population. METHODS: Phenotype data on 830 non-Hispanic white, 127 non-Hispanic African American, and 169 Hispanic IBD patients, recruited from six academic centers, were abstracted from medical records and compiled in the NIDDK-IBD Genetics Consortium repository. We characterized racial differences in family history, disease location and behavior, surgical history, and extraintestinal manifestations (EIMs) using standardized definitions. RESULTS: African American CD patients were more likely than whites to develop esophagogastroduodenal CD (OR = 2.8; 95% CI: 1.4-5.5), colorectal disease (OR = 1.9; 95% CI: 1.1-3.4), perianal disease (OR = 1.7; 95% CI: 1.03-2.8), but less likely to have ileal involvement (OR = 0.55; 95% CI: 0.32-0.96). They were also at higher risk for uveitis (OR = 5.5; 95% CI: 2.3-13.0) and sacroiliitis (OR = 4.0; 95% CI: 1.55-10.1). Hispanics had higher prevalence of perianal CD (OR = 2.9; 95% CI: 1.8-4.6) and erythema nodosum (3.3; 95% CI: 1.7-6.4). Among UC patients, Hispanics had more proximal disease extent. Both African American and Hispanic CD patients, but not UC patients, had lower prevalences of family history of IBD than their white counterparts. CONCLUSIONS: There are racial differences in IBD family history, disease location, and EIMs that may reflect underlying genetic variations and have important implications for diagnosis and management of disease. These findings underscore the need for further studies in minority populations.

Kane SV, Sandborn WJ, Rufo PA, Zholudev A, Boone J, Lyerly D, Camilleri M, Hanauer SB. · University of Chicago, Chicago, Illinois 60637, USA. · Am J Gastroenterol. · Pubmed #12818275 No free full text.

Abstract: OBJECTIVE: Lactoferrin is a glycoprotein expressed by activated neutrophils. The aim of this study was to determine the sensitivity and specificity of fecal lactoferrin concentrations for inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) versus healthy controls. METHODS: Fresh stool samples were collected from outpatients with ulcerative colitis (UC), Crohn's disease (CD), or IBS. Clinical disease activity for IBD was assessed using a modified Harvey-Bradshaw Activity Index. Fecal lactoferrin concentrations were determined using a polyclonal antibody-based enzyme linked immunoassay. Mean fecal lactoferrin concentrations for each group and sensitivity and specificity of the assay were determined. RESULTS: One hundred-four CD patients, 80 UC patients, 31 IBS patients, and 56 healthy controls were recruited. The mean +/- SE fecal lactoferrin concentration (microg/g fecal weight) was 440 +/- 128 for CD patients, 1125 +/- 498 for UC patients, 1.27 +/- 0.29 for IBS patients, and 1.45 +/- 0.4 for healthy controls. Fecal lactoferrin was 90% specific for identifying inflammation in patients with active IBD. Elevated fecal lactoferrin was 100% specific in ruling out IBS. CONCLUSIONS: Fecal lactoferrin is sensitive and specific for detecting inflammation in chronic IBD. This noninvasive test may prove useful in screening for inflammation in patients presenting with abdominal pain and diarrhea.

Kane SV, Cohen RD, Aikens JE, Hanauer SB. · Department of Medicine, University of Chicago, Illinois, USA. · Am J Gastroenterol. · Pubmed #11693328 No free full text.

Abstract: OBJECTIVE: There are scant data regarding outpatient adherence in quiescent ulcerative colitis aside from patients enrolled in controlled clinical trials. We conducted a prevalence study to determine the medication adherence rate of maintenance therapy and to identify possible risk factors for nonadherence. METHODS: Outpatients with clinically quiescent ulcerative colitis for >6 months on maintenance mesalamine (Asacol, Procter and Gamble, Cincinnati, OH) were eligible. Patients were interviewed regarding disease history, and demographics were obtained from medical records. Refill information for at least 6 months was obtained from computerized pharmacy records. Adherence was defined as at least 80% consumption of supply dispensed. Using nonadherence as the outcome of interest, stratified analysis and regression modeling were used to identify significant associations. RESULTS: Data were complete for the 94 patients recruited. The overall adherence rate was found to be 40%. The median amount of medication dispensed per patient was 71% (8-130%) of the prescribed regimen. Nonadherent patients were more likely to be male (67% vs 52%, p < 0.05), single (68% vs 53%, p = 0.04), and to have disease limited to the left side of the colon versus pancolitis (83% vs 51%, p < 0.01). Sixty-eight percent of patients who took more than four prescription medications were found to be nonadherent versus only 40% of those patients taking fewer medications (p = 0.05). Age, occupation, a family history of inflammatory bowel disease, length of remission, quality-of-life score, or method of recruitment (telephone interview vs clinical visit) were not associated with nonadherence. Logistic regression identified that a history of more than four prescriptions (odds ratio [OR] 2.5 [1.4-5.7]) and male gender (OR 2.06 [1.17-4.88]) increased the risk of nonadherence. Two statistically significant variables, which were protective against nonadherence, were endoscopy within the past 24 months (OR 0.96 [0.93-0.99]) and being married (OR 0.46 [0.39-0.57]). CONCLUSION: Nonadherence is associated with multiple concomitant medications, male gender, and single status. These patient characteristics may be helpful in targeting those patients at higher risk for nonadherence.