The committee will discuss supplemental new drug application (sNDA) 203214 supplement 18, XELJANZ (tofacitinib) tablets, submitted by Pfizer Inc., proposed for the treatment of adult patients with moderately to severely active ulcerative colitis who have demonstrated an

Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder that significantly reduces patients' quality of life. Advances in diagnostic testing and in therapeutic options for patients with IBS led to the development of this first-ever American College of Gastroenterology clinical guideline for the management of IBS using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Twenty-five clinically important questions were assessed after a comprehensive literature search; 9 questions focused on diagnostic testing; 16 questions focused on therapeutic options. Consensus was obtained using a modified Delphi approach, and based on GRADE methodology, we endorse the following: We suggest that a positive diagnostic strategy as compared to a diagnostic strategy of exclusion be used to improve time to initiating appropriate therapy. We suggest that serologic testing be performed to rule out celiac disease in patients with IBS and diarrhea symptoms. We suggest that fecal calprotectin be checked in patients with suspected IBS and diarrhea symptoms to rule out inflammatory bowel disease. We recommend a limited trial of a low fermentable oligosaccharides, disacchardies, monosaccharides, polyols (FODMAP) diet in patients with IBS to improve global symptoms. We recommend the use of chloride channel activators and guanylate cyclase activators to treat global IBS with constipation symptoms. We recommend the use of rifaximin to treat global IBS with diarrhea symptoms. We suggest that gut-directed psychotherapy be used to treat global IBS symptoms. Additional statements and information regarding diagnostic strategies, specific drugs, doses, and duration of therapy can be found in the guideline.

Small intestinal bacterial overgrowth is defined as the presence of excessive numbers of bacteria in the small bowel, causing gastrointestinal symptoms. This guideline statement evaluates criteria for diagnosis, defines the optimal methods for diagnostic testing, and summarizes treatment options for small intestinal bacterial overgrowth. This guideline provides an evidence-based evaluation of the literature through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the available evidence was not appropriate for a formal GRADE recommendation, key concepts were developed using expert consensus.

BACKGROUND & AIMS Patients with inflammatory bowel disease (IBD) are at risk for certain malignancies. We aimed to determine the risk of melanoma and nonmelanoma skin cancer (NMSC) in patients with IBD and how medications affect these risks. METHODS We performed retrospective cohort and nested case-control studies using administrative data from the LifeLink Health Plan Claims Database from 1997 to 2009. The cohort comprised 108,579 patients with IBD, and each was matched to 4 individuals without IBD. The risk of melanoma and NMSC was evaluated by incidence rate ratio (IRR) and by adjusted Cox proportional hazard ratio (HR) modeling. In nested case-control studies, patients with melanoma or NMSC were matched to 4 patients with IBD without melanoma or NMSC. Conditional logistic regression was used to determine associations between medications and both skin cancers. RESULTS In the cohort, IBD was associated with an increased incidence of melanoma (IRR, 1.29; 95% confidence interval [CI], 1.09–1.53). Risk was greatest among individuals with Crohn’s disease (IRR, 1.45; 95% CI, 1.13–1.85; adjusted HR, 1.28; 95% CI, 1.00–1.64). The incidence of NMSC also increased among patients with IBD (IRR, 1.46; 95% CI, 1.40–1.53) and was greatest among those with CD (IRR, 1.64; 95% CI, 1.54–1.74). In the nested case-control studies, therapy with biologics increased the risk of melanoma (odds ratio [OR], 1.88; 95% CI, 1.08–3.29). Patients who had been treated with thiopurines had an increased risk of NMSC (OR, 1.85; 95% CI, 1.66–2.05). CONCLUSIONS Immunosuppression increases the risk of melanoma and NMSC among patients with IBD. The risk of melanoma is increased by use of biologics, and the risk of NMSC is increased by use of thiopurines. Patients with IBD should be counseled and monitored for skin cancer.

Background & Aims-Patients with inflammatory bowel disease (IBD) might be at increased risk for certain malignancies. We evaluated the risk of non-melanoma skin cancer (NMSC) in patients with IBD and determined how immunosuppressive and biologic medications affect this risk.

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Background There are insufficient data to make firm dietary recommendations for patients with inflammatory bowel disease (IBD). Yet patients frequently report that specific food items influence their symptoms. In this study, we describe patients’ perceptions about the benefits and harms of selected foods and patients’ dietary patterns. Methods CCFA Partners is an ongoing internet-based cohort study of patients with IBD. We used a semi-quantitative food frequency questionnaire to measure dietary consumption patterns and open-ended questions to elicit responses from patients about food items they believe ameliorate or exacerbate IBD. We categorized patients into four mutually exclusive disease categories: CD without an ostomy or pouch (CD), UC without an ostomy or pouch (UC), CD with an ostomy (CD-ostomy), and UC with a pouch (UC-pouch). Results Yogurt, rice, and bananas were more frequently reported to improve symptoms whereas non-leafy vegetables, spicy foods, fruit, nuts, leafy vegetables, fried foods, milk, red meat, soda, popcorn, dairy, alcohol, high-fiber foods, corn, fatty foods, seeds, coffee, and beans were more frequently reported to worsen symptoms. Compared to CD patients, CD-ostomy patients reported significantly greater consumption of cheese (odds ratio (OR) 1.56, 95% CI 1.03–2.36), sweetened beverages (OR 2.14, 95% CI 1.02–1.03), milk (OR 1.84, 95% CI 1.35–2.52), pizza (OR 1.57, 95% CI 1.12–2.20), and processed meats (OR 1.40; 95% CI 1.04–1.89). Conclusions Patients identified foods that they believe worsen symptoms and restricted their diet. Patients with ostomies ate a more liberal diet. Prospective studies are needed to determine whether diet influences disease course.

Background & Aims Data regarding the risk of gastrointestinal and extra-intestinal cancers in Crohn’s disease (CD) and ulcerative colitis (UC) are needed to understand the clinical course of inflammatory bowel diseases (IBDs) and their treatments. Methods We performed a nationwide historical cohort study using Danish healthcare databases. We identified patients with a diagnosis of CD or UC, recorded from 1978 through 2010, and followed them until first occurrence of cancer, death, or emigration. We used standardized incidence ratios (SIRs) to compare cancer incidence in CD and UC patients to that expected in the general population. Results Excluding cancers diagnosed within 1 year of IBD diagnosis, 772 cases of invasive cancer occurred among 13,756 patients with CD (SIR, 1.3; 95% confidence interval [CI], 1.2–1.4) and 2331 occurred among 35,152 patients with UC (SIR, 1.1; 95% CI, 1.0–1.1). CD was weakly associated with gastrointestinal cancers (SIR 1.2; 95% CI, 1.0–1.4) and extra-intestinal cancers (SIR, 1.3; 95% CI, 1.2–1.4), with the strongest associations for hematological malignancies (SIR, 1.9; 95% CI, 1.5–2.3), smoking-related cancers (SIR 1.5, 95% CI 1.3–1.8), and melanoma (SIR, 1.4; 95% CI, 1.0–1.9). Associations between UC and gastrointestinal and extra-intestinal cancers were weaker (SIR, 1.1; 95% CI, 1.0–1.2 and SIR, 1.1; 95% CI, 1.0–1.1, respectively). The relative risk of extra-intestinal cancers among patients with IBD was relatively stable over time, although the risk of gastrointestinal cancers decreased. Conclusions Patients with IBD, particularly CD, are at increased risk for gastrointestinal and extra-intestinal malignancies. The relative risk of gastrointestinal malignancy has deceased since 1978, without a concomitant increase in the risk of non-gastrointestinal malignancy.