Millie D. Long

Risk of Melanoma and Nonmelanoma Skin Cancer Among Patients With Inflammatory Bowel Disease

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 Crohns 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.

Increased Risk for Non-Melanoma Skin Cancer in Patients With Inflammatory Bowel Disease

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. METHODS We performed retrospective cohort and nested case-control studies by using administrative data from PharMetrics Patient Centric Database. In the cohort study, 26,403 patients with Crohns disease (CD) and 26,974 patients with ulcerative colitis (UC) were each matched to 3 non-IBD controls. NMSC risk was evaluated by incidence rate ratio (IRR). In the nested case-control study, 387 CD patients and 355 UC patients with NMSC were each matched to 4 IBD patients without NMSC by using incidence density sampling. Conditional logistic regression was used to determine the association between specific IBD medication use and NMSC. RESULTS In the cohort study, the incidence of NMSC was higher among patients with IBD compared with controls (IRR, 1.64; 95% confidence interval [CI], 1.51-1.78). In the nested-case control study, recent thiopurine use (< or =90 days) was associated with NMSC (adjusted odds ratio [OR], 3.56; 95% CI, 2.81-4.50), as was recent biologic use among patients with CD (adjusted OR, 2.07; 95% CI, 1.28-3.33). Persistent thiopurine use (>365 days) was associated with NMSC (adjusted OR, 4.27; 95% CI, 3.08-5.92), as was persistent biologic use among patients with CD (adjusted OR, 2.18; 95% CI, 1.07-4.46). CONCLUSIONS Patients with IBD, especially those who receive thiopurines, are at risk for NMSC. Appropriate counseling and monitoring of such patients with IBD are recommended.

Prevalence and epidemiology of overweight and obesity in children with inflammatory bowel disease

Background: Obesity is a significant public health threat to children in the United States. The aims were to: 1) Determine the prevalence of obesity in a multicenter cohort of children with inflammatory bowel disease (IBD); 2) Evaluate whether overweight and obese status is associated with patient demographics or disease characteristics. Methods: We used data from the ImproveCareNow Collaborative for pediatric IBD, a multicenter registry of children with IBD, collected between April 2007 and December 2009. Children ages 2–18 years were classified into body mass index (BMI) percentiles. Bivariate analyses and multivariate logistic regression were used to compare demographic and disease characteristics by overweight (BMI >85%) and obese (BMI >95%) status. Results: The population consisted of 1598 children with IBD. The prevalence of overweight/obese status in pediatric IBD is 23.6%, (20.0% for Crohns disease [CD] and 30.1% for ulcerative colitis [UC] and indeterminate colitis [IC]). African American race (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.10–2.48) and Medicaid insurance (OR 1.67, 95% CI 1.19–2.34) were positively associated with overweight/obese status. Prior IBD‐related surgery (OR 1.73, 95% CI 1.07–2.82) was also associated with overweight and obese status in children with CD. Other disease characteristics were not associated with overweight and obesity in children with IBD. Conclusions: Approximately one in five children with CD and one in three with UC are overweight or obese. Rates of obesity in UC are comparable to the general population. Obese IBD patients may have a more severe disease course, as indicated by increased need for surgery. Sociodemographic risk factors for obesity in the IBD population are similar to those in the general population. (Inflamm Bowel Dis 2010;)

A clinical review of recent findings in the epidemiology of inflammatory bowel disease

Inflammatory bowel diseases (IBD), including both Crohn’s disease and ulcerative colitis, are disorders of chronic inflammation of the gastrointestinal tract marked by episodes of relapse and remission. Over the past several decades, advances have been made in understanding the epidemiology of IBD. The incidence and prevalence of both Crohn’s disease and ulcerative colitis have been increasing worldwide across pediatric and adult populations. As IBD is thought to be related to a combination of individual genetic susceptibility, environmental triggers, and alterations in the gut microbiome that stimulate an inflammatory response, understanding the potentially modifiable environmental risk factors associated with the development or the course of IBD could impact disease rates or management in the future. Current hypotheses as to the development of IBD are reviewed, as are a host of environmental cofactors that have been investigated as both protective and inciting factors for IBD onset. Such environmental factors include breast feeding, gastrointestinal infections, urban versus rural lifestyle, medication exposures, stress, smoking, and diet. The role of these factors in disease course is also reviewed. Looking forward, there is still much to be learned about the etiology of IBD and how specific environmental exposures intimately impact the development of disease and also the potential for relapse.

Risk of Cancer in Patients With Inflammatory Bowel Diseases: A Nationwide Population-based Cohort Study With 30 Years of Follow-up Evaluation

BACKGROUND & AIMS Data regarding the risk of gastrointestinal and extraintestinal cancers in Crohns 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 health care databases. We identified patients with a diagnosis of CD or UC, recorded from 1978 through 2010, and followed them up until the first occurrence of cancer, death, or emigration. We used standardized incidence ratios (SIRs) to compare cancer incidence in CD and UC patients with 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 associated weakly with gastrointestinal cancers (SIR, 1.2; 95% CI, 1.0-1.4) and extraintestinal cancers (SIR, 1.3; 95% CI, 1.2-1.4), with the strongest associations for hematologic 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 extraintestinal 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 extraintestinal 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 extraintestinal malignancies. The relative risk of gastrointestinal malignancy has decreased since 1978, without a concomitant increase in the risk of nongastrointestinal malignancy.

Sleep disturbance and risk of active disease in patients with Crohn's disease and ulcerative colitis.

BACKGROUND & AIMS Impairment of sleep quality is common in patients with inflammatory bowel diseases (IBDs) (eg, Crohns disease [CD] and ulcerative colitis [UC]), even during clinical remission. Sleep impairment can activate inflammatory pathways. Few prospective studies have examined the role of sleep disturbance on risk of relapse in IBD. METHODS We analyzed data from 3173 patients with IBD (1798 in clinical remission at baseline) participating in the Crohns and Colitis Foundation of America Partners study, a longitudinal, Internet-based cohort. Sleep disturbance was measured using a subset of questions from the Patient Reported Outcomes Measurement Information Systems sleep disturbance questionnaire. Disease activity was assessed using the short Crohns Disease Activity Index and the simple clinical colitis activity index for CD and UC, respectively. Logistic regression was used to identify predictors of sleep quality and examine the effect of sleep quality at baseline among patients in remission on risk of active disease at 6 months. RESULTS Disease activity, depression, female sex, smoking, and use of corticosteroids or narcotics were associated with sleep disturbance at enrollment. Among 1291 patients whose CD was in remission at baseline, those with impaired sleep had a 2-fold increase in risk of active disease at 6 months (adjusted odds ratio, 2.00; 95% confidence interval, 1.45-2.76); however, no effect was observed in patients with UC (odds ratio, 1.14; 95% confidence interval, 0.75-1.74). These findings persisted in a number of sensitivity analyses. CONCLUSIONS Sleep disturbance was associated with an increased risk of disease flares in CD but not UC. These findings indicate that the evaluation and treatment of sleep disturbance in patients with CD might improve outcomes.

Evaluation of the patient-reported outcomes measurement information system in a large cohort of patients with inflammatory bowel diseases.

BACKGROUND & AIMS Patient-reported outcomes (PROs) convey important aspects of health status, complementing physician-reported measures. The PRO Measurement Information System (PROMIS) provides valid, widely available measures applicable to patients with chronic illness and the general population. We sought to evaluate these measures in a large cohort of patients with inflammatory bowel disease (IBD). METHODS By using data from the Crohns and Colitis Foundation Association Partners internet cohort, we performed cross-sectional and longitudinal analyses to evaluate associations between PROMIS measures and validated disease activity indices (Short Crohns Disease Activity Index and Simple Clinical Colitis Activity Index) and the Short IBD Questionnaire quality-of-life instrument. RESULTS A total of 10,634 individuals (6689 with Crohns disease and 3945 with ulcerative colitis or indeterminate colitis) completed PRO testing. Compared with the general population (mean PROMIS score, 50), IBD patients in this cohort reported more depression (mean, 54), anxiety (mean, 52), fatigue (mean, 56), sleep disturbance (mean, 52), and pain interference (mean, 53); and they had less social satisfaction (mean, 48). In each PROMIS domain, there was worse functioning with increasing levels of disease activity and worsening Short IBD Questionnaire scores (P < .001 for all). Longitudinal analyses showed improved PROMIS scores with improved disease activity and worsening PROMIS scores with worsening disease (P < .001 for all comparisons). CONCLUSIONS In a cross-sectional and longitudinal study, we observed differences between patients with IBD and the general population in several important aspects of health. The improvement in diverse health outcome measures with improved disease control provides strong support for the construct validity of PROMIS measures in the IBD population. Their use should advance patient-centered outcomes research in IBD.

Increased risk of herpes zoster among 108 604 patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) on certain immunosuppressants have increased herpes zoster (HZ) risk.

Development of an internet-based cohort of patients with inflammatory bowel diseases (CCFA Partners): Methodology and initial results

Background: The widespread use of the Internet allows for unique research opportunities. We aimed to develop and follow an Internet‐based cohort (e‐cohort) of patients with self‐reported inflammatory bowel diseases (IBD) over time. Methods: We established an e‐cohort of adults with IBD (CCFA Partners) by recruiting through Crohns and Colitis Foundation of America (CCFA) email rosters, CCFA Website promotion, social media, and other publicity mechanisms. The baseline survey included modules on disease course and activity, diet and exercise, and patient‐reported outcomes (PROs). Baseline characteristics of the cohort are summarized using descriptive statistics. Results: A total of 7819 adults with IBD joined CCFA Partners through August, 2011. The median age was 42 years (interquartile range [IQR] 30–54), 5074 (72.3%) were female. A total of 4933 (63.1%) had Crohns disease (CD), 2675 (34.2%) had ulcerative colitis (UC), and 211 (2.7%) had IBD unspecified. For CD, the mean short CD Activity Index (CDAI) was 151.9 (standard deviation [SD] 106.4), with 2274 (59.4%) in remission. For UC, the mean simple clinical colitis activity index (SCCAI) was 3.6 (SD 2.8), with 937 (42.9%) in remission. The mean short IBD questionnaire (SIBDQ) score was 48.7 (SD 11.8). SIBDQ was inversely correlated with disease activity (P < 0.01). The mean Morisky medication adherence score (MMAS) was 5.7 (SD 2.0). MMAS scores were inversely correlated with disease activity (P < 0.01). Conclusions: CCFA Partners is a novel e‐cohort. Enrollment is ongoing, with surveys twice yearly. CCFA Partners represents a unique resource to study PROs and changes in disease management over time. (Inflamm Bowel Dis 2012;)

Inflammatory bowel disease, irritable bowel syndrome, or what?: A challenge to the functional-organic dichotomy.

Many patients with inflammatory bowel disease (IBD) in clinical remission continue to have symptoms of pain and diarrhea despite minimal or no ongoing inflammation. These patients may be considered to have an overlap of IBD and irritable bowel syndrome (IBD-IBS). In this months Journal, a proposal is made that continued symptoms in patients with elevated calprotectin, a marker of inflammation, is related to IBD. We propose an alternate biopsychosocial model whereby mutual effects of peripheral and central factors influence symptom generation in both IBD and IBS. Understanding this model has important implications for treatment of patients with IBD-IBS.