Ioannis Oikonomou

Risk Factors for Clinical Phenotypes of Crohn's Disease of the Ileal Pouch

BACKGROUND:Crohns disease (CD) of the pouch can occur in patients with colectomy and ileal pouch-anal anastomosis (IPAA) originally performed for a preoperative diagnosis of ulcerative colitis. The clinical presentations of CD of the pouch are inflammatory, fibrostenotic, and fistulizing. Risk factors for clinical phenotypes of CD of the pouch have not been characterized.METHODS:A total of 78 eligible patients with CD of the pouch together with 294 nonselected non-CD patients with IPAA seen in the Pouchitis Clinic were enrolled, including 28 with inflammatory CD, 18 with fibrostenotic CD, and 32 with fistulizing CD. The clinical phenotypes of CD were diagnosed based on a combined assessment of clinical, endoscopic, radiographic, and histologic features. Three separate analyses were performed, and for each analysis, the outcome of interest was having one of the phenotypes versus not having it. A stepwise selection multivariable logistic regression analysis was used.RESULTS:In the multivariable analysis, the risk factor for inflammatory CD was higher afferent-limb endoscopy scores (hazard ratio [HR] 1.87 95% confidence interval [CI] 1.54–2.27); the risk factors for fibrostenotic CD were higher afferent-limb (95% CI 1.81–3.48, HR 2.51) and higher cuff (95% CI 1.01–1.84, HR 1.36) endoscopy scores; and for fistulizing CD the risk factors were younger age (95% CI 0.93–0.99, HR 0.96), female gender (95% CI 1.35–6.97, HR 3.07), a preoperative diagnosis of indeterminate colitis (95% CI 1.72–9.34, HR 4.00), and no use of nonsteroidal antiinflammatory drugs (95% CI 1.31–8.25, HR 3.28).CONCLUSIONS:Each of the three phenotypes of CD of the pouch was associated with certain risk factors, suggesting that each of these diseases has a different etiology and disease process. The identification and management of some of the modifiable risk factors may reduce CD-related morbidity.

The influence of depression on quality of life in patients with inflammatory bowel disease.

Background: Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that significantly impacts the health-related quality of life (HR-QOL). A decreased HR-QOL has been demonstrated in patients with active disease compared with patients in remission. In this cross-sectional study, we examined the role of depression and disease activity as independent factors in predicting patient’s HR-QOL. Methods: Hundred and five patients with either Crohn’s disease (CD) or ulcerative colitis (UC) were enrolled. Disease activity was evaluated using Crohn’s Disease Activity Index or Seo’s Activity Index. Depressive symptoms were evaluated using Beck’s Depression Inventory-II and Beck’s Depression Inventory for Primary Care (BDI-PC). HR-QOL was evaluated using the Short Inflammatory Bowel Disease Questionnaire. Simple and multiple regressions were performed on quality of life score with demographic and clinical variables as predictors. Results: The prevalence of depression in our study population is 25%. In patients with both CD and UC, depression is the most significant predictor to a poor HR-QOL (in CD, P = 8.22 × 10−6; in UC, P = 2.02 × 10−6). HR-QOL is weakly affected by disease activity (in CD, P = 0.110; in UC, P = 0.00492). In CD, biological use displays positive effect on HR-QOL (P = 0.00780). In total, the proportion of variance explained by all predictors is 61% for CD and 53% for UC, whereas the depression alone explains 44% and 36%. Conclusions: Our study demonstrates the importance of depression toward the quality of life in patients with inflammatory bowel disease. The diagnosis of depression should be actively sought out and treated in outpatient inflammatory bowel disease practices.

Risk factors for low bone mass in patients with ulcerative colitis following ileal pouch-anal anastomosis.

OBJECTIVES:Bone mineral density (BMD) can be adversely affected by the chronic nature of inflammatory bowel disease. Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with ulcerative colitis (UC) who require proctocolectomy. There are few data on BMD in UC patients with IPAA. The aim of the study was to assess the prevalence and risk factors associated with low BMD in UC patients after IPAA.METHODS:A total of 327 eligible patients with UC and IPAA from the Pouchitis Clinic were enrolled. Dual-energy X-ray absorptiometry was performed. Patients were classified as having normal or low BMD, based on the criteria by the International Society for Clinical Densitometry. A total of 39 demographic and clinical variables were evaluated with logistic regression models.RESULTS:Of 327 patients with a median of 4 years after IPAA, 105 (32.1%) had low BMD. Fragility fracture was documented in 11 patients (10.5%) in the low BMD group and in 13 of 222 patients (5.9%) in the normal BMD group (P=0.14). In the multivariable analysis, covariate-adjusted factors associated with a low BMD were advanced age (odds ratio (OR) =1.64 per 5 years; 95% CI, 1.44–1.87), low body mass index (OR=0.43 per 5 kg/m2; 95% CI, 0.30–0.62), and non-use of daily calcium supplement (OR=0.53; 95% CI, 0.29–0.96). Pouch-associated factors were not found to be significantly associated with the bone loss.CONCLUSIONS:Low BMD was common in patients with UC, even after colectomy and IPAA. Low BMD in this patient population was associated with certain risk factors, some of which may be modifiable.

Clinical, serologic, and genetic factors associated with pyoderma gangrenosum and erythema nodosum in inflammatory bowel disease patients

Background:Pyoderma gangrenosum (PG) and erythema nodosum (EN) are the most common cutaneous manifestations of inflammatory bowel disease (IBD) but little is known regarding their etiopathogenesis. Methods:We performed a case–control study comparing characteristics between IBD patients with a documented episode of PG (PG+) and/or EN (EN+) with those without PG (PG−) and EN (EN−). Data on clinical features were obtained by chart review. IBD-related serology was determined using enzyme-linked immunosorbent assay and genome-wide data generated using Illumina technology. Standard statistical tests for association were used. Results:We identified a total of 92 cases of PG and 103 cases of EN with genetic and clinical characteristics, of which 64 PG and 55 EN cases were available for serological analyses. Fewer male subjects were identified in the PG(+) (odds ratio 0.6, P = 0.009) and EN(+) groups (odds ratio 0.31, P = 0 < 0.0001). Colonic disease, previous IBD-related surgery, and noncutaneous extra-intestinal manifestations were more common among both PG(+) and EN(+) patients compared with controls. PG(+) was associated with anti-nuclear cytoplasmic antibody seropositivity (P = 0.03) and higher anti-nuclear cytoplasmic antibody level (P = 0.02) in Crohns disease. Genetic associations with PG included known IBD loci (IL8RA [P = 0.00003] and PRDM1 [0.03]) as well as with USP15 (4.8 × 10−6) and TIMP3 (5.6 ×10−7). Genetic associations with EN included known IBD susceptibility genes (PTGER4 [P = 8.8 × 10−4], ITGAL [0.03]) as well as SOCS5 (9.64 × 10−6), CD207 (3.14 × 10−6), ITGB3 (7.56 × 10−6), and rs6828740 (4q26) (P < 5.0 × 10−8). Multivariable models using clinical, serologic, and genetic parameters predicted PG (area under the curve = 0.8) and EN (area under the curve = 0.97). Conclusion:Cutaneous manifestations in IBD are associated with distinctive genetic characteristics and with the similar clinical characteristics, including the development of other extra-intestinal manifestations suggesting shared and distinct etiologies.

The inflammatory bowel disease Live Interinstitutional and Interdisciplinary Videoconference Education (IBD LIVE) series

Background:Managing patients with inflammatory bowel disease requires multidisciplinary coordination. Technological advances have enhanced access to care for patients and improved physician interactions. The primary aim of our project was to convene diverse institutions and specialties through a multisite virtual conferencing platform to discuss complex patient management. Methods:The case conference is designed to include multiple institutions to exchange ideas, review evidence-based data, and provide input on the management of patients with Crohns disease and ulcerative colitis. Technology is supplied and coordinated by an information technology specialist and Chorus Call, Inc., an international teleconferencing service provider. The Inflammatory Bowel Disease Live Interinstitutional Interdisciplinary Videoconference Education (IBD LIVE) initiative is accredited by the University of Pittsburgh Medical Center (UPMC) Center for Continuing Education in the Health Sciences for 1 AMA PRA Category 1 Credit per weekly session. Results:IBD LIVE began in 2009 comprising only adult gastroenterology and pediatric gastroenterology from UPMC Presbyterian and Childrens Hospitals. Participation steadily increased from 5 sites in 2010 to 11 sites in 2014. Maximum attendance for a single conference was 73 participants with a median of 48. The Continuing Medical Education scores (1 = worst to 5 = best) have a high median overall score (4.6, range 3.2–5.0) with positive responses with regard to the degree to which the conference changed practice. Conclusions:IBD LIVE has been successful and continues to grow. Implementation of the Crohns and Colitis Foundation of America Virtual Preceptor Program using the IBD LIVE platform will provide expanded national physician access to this professional education activity.

Human placenta-derived cells (PDA-001) for the treatment of moderate-to-severe Crohn's disease: A phase 1b/2a study

Background:PDA-001 (cenplacel-L), a preparation of placenta-derived mesenchymal-like adherent cells with immunomodulatory effects, previously demonstrated safety and tolerability in an open-label Crohns disease (CD) study. The current phase 1b/2a study evaluated the safety and efficacy of PDA-001 in subjects with moderate-to-severe CD. Methods:Subjects had active inflammation on colonoscopy or elevated fecal calprotectin and inadequate response to conventional therapy. Concomitant therapy with stable doses of immunomodulators and/or biologics was permitted. Subjects received 8 units of PDA-001 (1.5 × 108 cells per unit) in the phase 1b open-label study. In the phase 2a double-blind study, subjects were randomly assigned placebo, 1 unit, or 4 units of PDA-001 (2 infusions 1 wk apart). The primary endpoint was induction of clinical response (≥100 points and/or 25% decrease in Crohns Disease Activity Index) at 4 and 6 weeks. Results:Fifty subjects were enrolled (safety analysis, 50 subjects; efficacy analysis, 48 subjects). Four subjects received 8 units of PDA-001 (phase 1b study); 46 subjects were subsequently randomized to 1 or 4 units of PDA-001 or placebo (phase 2a study). The primary endpoint was achieved in 10/28 (36%) of PDA-001 subjects compared with placebo (0%, P = 0.026). Clinical remission was achieved in 4/28 (14%) of PDA-001 subjects compared with placebo (0%, P = 0.3). One treatment-related serious adverse event occurred (systemic hypersensitivity reaction at 8 units). In the phase 2a study, serious adverse events occurred in 9/28 (32%) of PDA-001 subjects and 1/16 (7%) of placebo subjects. Conclusions:A 2-infusion regimen of PDA-001 induced clinical response in subjects with moderate-to-severe CD. Additional studies are warranted.

Colitis Following Initiation of Sofosbuvir and Simeprevir for Genotype 1 Hepatitis C.

Sofosbuvir and simeprevir are used for the treatment of chronic hepatitis C (HCV) genotype 1. Both drugs have been well-tolerated, with diarrhea noted in 6% cases with sofosbuvir, 16% with sofosbuvir plus simeprevir, and 0% with simeprevir. No prior reports exist of colitis secondary to either drug or their combination. We report a patient with no prior history of inflammatory bowel disease who developed significant bloody diarrhea within 2 weeks of sofosbuvir/simeprevir initiation. Colonoscopy and biopsy confirmed pancolitis, which responded to mesalamine and completion of sofosbuvir/simeprevir.

IBD LIVE Case Series–Case 2: Previous Cancer in a Patient with Crohn's Disease: Is It Appropriate to Use Biologics and Immunosuppressants for IBD Treatment?

Article first published online 4 May 2015.

23 EMERGENT COLECTOMY RATES DECREASED WHILE ELECTIVE IPAA RATES WERE STABLE OVER TIME: A NATIONWIDE INPATIENT SAMPLE STUDY

Purpose Despite advances in biologic therapy, approximately 10–15% of ulcerative colitis (UC) patients require surgery. We aimed to (1) examine the rates of emergent colectomy and elective ileal pouch anal anastomosis (IPAA) over time among UC patients in the USA and (2) investigate disparities in surgery rates by patient demographics.

Cyclosporine: does it matter if it is given for Crohn's colitis or ulcerative colitis?

Crohn’s disease can affect any part of the digestive tract. About one fourth of patients present with Crohn’s colitis and half of the patients present with ileocecal involvement.1 Our armamentarium of drugs for moderate to severe colonic Crohn’s disease includes corticosteroids, immunomodulators such as azathioprine, or methotrexate and anti-TNF agents. Cyclosporine has been used in specialized centers for the treatment of acute severe ulcerative colitis but has been rarely used for the management of Crohn’s disease. In this issue of Journal of Clinical Gastroenterology, Lazarev et al2 present a retrospective cohort study evaluating the use of cyclosporine in patients with Crohn’s colitis. In ulcerative colitis, cyclosporine is used as a bridge therapy to thiopurines. In acute severe ulcerative colitis, the response rate to cyclosporine has been reported to be up to 85%.3 The long-term benefit of cyclosporine in ulcerative colitis in terms of avoidance of colectomy is questionable. A study of patients successfully treated with cyclosporine has shown that the probability of avoiding colectomy was 63% at 1 year that dropped to 12% at 7 years.4 The use of cyclosporine in ulcerative colitis has further been limited by its side-effect profile.5 What happens in Crohn’s colitis? Do patients with Crohn’s colitis respond in a similar manner to intravenous (IV) cyclosporine as patients with ulcerative colitis? The study by Lazarev and colleagues aims to give us an answer. This was a retrospective chart review evaluating the role of IV cyclosporine in the management of patients with Crohn’s colitis or indeterminate colitis (IC) favoring Crohn’s disease. Primary endpoint was the colectomy rate during an inpatient admission for IV cyclosporine. Secondary endpoints were the colectomy-free survival at 6 and 12 months after the initial admission for IV cyclosporine. This was the largest reported cohort of patients with Crohn’s colitis treated with cyclosporine. Within a 12.5-year period, 41 patients with Crohn’s colitis and 7 patients with IC favoring Crohn’s disease who were treated with IV cyclosporine were identified. The median follow-up time was 12 months (range, 1 to 128mo). The follow-up data on 2 patients were not available. Only 6 of 48 patients (12.5%) required colectomy during the initial hospitalization. The colectomy rate was higher in patients with IC favoring Crohn’s disease. Among 7 IC patients, 2 (28.6%) required colectomy. The long-term avoidance of colectomy was not as impressive. Similar to the data from ulcerative colitis trials, the colectomy rate increased significantly during follow-up.4 Almost half of the patients (52%) underwent colectomy during follow-up. The colectomy rate at 6 months was 28.2% and at 12 months 41.1%. Before the hospitalization, 85% of the patients had used immunomodulators and 69% had used an anti-TNF agent. Among multiple demographic and laboratory parameters as well as duration, location of disease, smoking status, prednisone, thiopurine and infliximab use, only anti-TNF use within 4 weeks before hospitalization predicted surgery with an odds ratio of 7.2. Three out of 6 patients who had colectomy were on anti-TNF agents recently, whereas there were no data available for 1 patient. Three patients received at least 1 subsequent course of IV cyclosporine after their hospitalization. The study was performed in an institution with a strong tradition in the use of cyclosporine. Among 620 patients treated with cyclosporine 91 had Crohn’s disease. About half of these patients were eligible for the study. The relatively small number of subjects and the heterogenous population precludes drawing a definitive conclusion. Some of the patients might have been hospitalized only for IV cyclosporine treatment requiring inpatient monitoring, without having severe Crohn’s colitis. Only 48% of the patients were on prednisone before admission, which points toward less severe disease. Mild to moderate Crohn’s disease activity can bias the study toward a lower probability for colectomy, which is the primary endpoint. Interestingly, the colectomy rate in patients with IC favoring Crohn’s was much