Efficacy of infliximab for extraintestinal manifestations of inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD), are associated with extraintestinal manifestations (EIMs) in approximately 40% of patients. Infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, is effective for induction and maintenance of remission of CD and UC. The role of infliximab for EIMs related to IBD has been less studied, but it is likely as effective. The EIMs may run a course that parallels IBD activity or may present separately. The EIMs that parallel intestinal inflammation (eg, peripheral arthritis, pyoderma gangrenosum, erythema nodosum, and episcleritis) generally respond to infliximab. Therefore, treating patients with IBD who have one of these EIMs will more often than not improve the EIM. The EIMs that run a separate course from IBD are more difficult to treat. Ankylosing spondylitis (AS), uveitis, and primary sclerosing cholangitis (PSC) have variable responses to IBD medications. Infliximab is efficacious for uveitis and is approved by the US Food and Drug Administration for treatment of AS. The efficacy of infliximab for PSC is unknown. The dosing schedule of infliximab for IBD patients with EIMs should be induction doses with 5 mg/kg at 0, 2, and 6 weeks followed by every 8 weeks. Whether long-term infliximab therapy is necessary to maintain remission of EIMs, as in the case of IBD, has not been established.

Infliximab dose intensification in Crohn's disease.

BACKGROUND: Crohn's disease (CD) patients who lose response to infliximab may benefit from an increase in dose or decrease in interval between infusions. The aims of this study were to determine the proportion of CD patients who require dose intensification and factors associated with dose intensification. METHODS: All CD patients who received at least 8 doses of infliximab at the University of Pittsburgh infusion center were included in an analysis to determine the need for dose intensification. Dose intensification was defined as either an increase in infliximab dose, a decrease in interval, or both. Factors were analyzed for association with dose intensification during follow-up. RESULTS: Between 2002 and 2005 there were 108 CD patients who received at least 8 infliximab doses. At 30 months from initial infusion, 69.1% were event-free from an interval decrease, 48.5% from a dose increase, and 45.7% from any dose intensification. Of the 54 patients who received dose intensification, 75.9% were able to regain response and remained on infliximab. The 30-month event-free rates did not differ by whether the patient had received prior infliximab therapy (P=0.49), had a lapse of more than 6 months between infusions (P=0.75), or were on concomitant immunomodulators (P=0.82). CONCLUSIONS: A significant proportion of CD patients on long-term infliximab treatment lose response and require an increase in dose and/or decrease in infusion interval. The majority of these patients regain response with dose intensification. Every-8-week maintenance infusions and concomitant immunomodulators did not alter the rate of infliximab dose intensification.

Assessment of reliability and validity of IBD phenotyping within the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) IBD Genetics Consortium (IBDGC).

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.