Edward V. Loftus Jr

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

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Publications (20)195.81 Total impact

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    ABSTRACT: To estimate the overall risk of cancer in a population-based cohort of patients with inflammatory bowel disease (IBD) and how IBD-related medications modify this risk. We identified all incident cancers (excluding nonmelanoma skin cancer) after IBD diagnosis in a cohort of 839 patients diagnosed as having IBD from January 1, 1940, through December 31, 2004, in Olmsted County, Minnesota, and followed up for a median 18 years through December 31, 2011 (122 patients taking biologic agents at last follow-up). We calculated standardized incidence ratios (SIRs) with 95% CIs of all cancers and compared cancer risk in patients treated with immunomodulators (IMMs) and biologics with that of patients not exposed to these medications, using an incidence rate ratio (IRR). One hundred nine patients developed 135 cancers. The 10-year cumulative probability of cancer was 3.8%. Patients with Crohn disease (SIR, 1.6; 95% CI, 1.2-2.1) but not ulcerative colitis (SIR, 1.1; 95% CI, 0.8-1.4) had an increased overall risk of cancer compared with the general population. Patients treated with IMMs (relative to IMM-naive patients) had an increased risk of melanoma (IRR, 5.3; 95% CI, 1.1-24.8) (and a numerically higher risk of hematologic malignant tumors [IRR, 4.2; 95% CI, 0.9-19.2]), although this risk returned to baseline on discontinuation of IMM treatment. Patients treated with biologics (relative to biologic-naive patients) had a numerically higher risk of hematologic malignant tumors (IRR, 5.3; 95% CI, 0.7-40.5). There was no significant increase in the risk of gastrointestinal malignancies in patients with IBD compared with the general population. We observed an increased risk of melanoma in IMM-treated patients with IBD, and this risk returned to baseline after discontinued use of the medications. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
    Mayo Clinic Proceedings 05/2015; 90(6). DOI:10.1016/j.mayocp.2015.03.024 · 6.26 Impact Factor
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    ABSTRACT: To study the comparative efficacy of biologic therapy in the management of biologic-naïve patients with Crohn disease (CD). We conducted a systematic review of randomized controlled trials published from January 1, 1985, through September 30, 2013, comparing biologic agents (infliximab [IFX], adalimumab [ADA], certolizumab pegol, natalizumab, vedolizumab, and ustekinumab) with each other or placebo for inducing and maintaining clinical remission in adults with moderate to severe CD. To increase comparability across trials, we focused on a subset of biologic-naïve patients for the induction end point and on responders to induction therapy for the maintenance end point. We followed a Bayesian network meta-analysis approach. We identified 17 randomized controlled trials of good methodological quality comparing 6 biologic agents with placebo, with no direct comparison of biologic agents. In network meta-analysis, we observed that IFX (relative risk [RR], 6.11; 95% credible interval [CrI], 2.49-18.29) and ADA (RR, 2.98; 95% CrI, 1.12-8.18), but not certolizumab pegol (RR, 1.48; 95% CrI, 0.76-2.93), natalizumab (RR, 1.36; 95% CrI, 0.69-2.86), vedolizumab (RR, 1.40; 95% CrI, 0.63-3.28), and ustekinumab (RR, 0.61; 95% CrI, 0.15-2.49), were more likely to induce remission than placebo. Similar results were observed for maintenance of remission. Infliximab had the highest probability of being ranked as the most efficacious agent for induction (86%) and ADA for maintenance of remission (48%). On the basis of network meta-analysis, IFX may be most efficacious agent for inducing remission in CD in biologic-naïve patients. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
    Mayo Clinic Proceedings 10/2014; 89(12). DOI:10.1016/j.mayocp.2014.08.019 · 6.26 Impact Factor
  • Jeanne Tung · Felicity T. Enders · Edward V. Loftus Jr
    Journal of Crohn s and Colitis 10/2014; 8(10). DOI:10.1016/j.crohns.2014.02.020 · 6.23 Impact Factor
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    ABSTRACT: Background & aims: There is a need for a scoring system that provides a comprehensive assessment of structural bowel damage, including stricturing lesions, penetrating lesions, and surgical resection, for measuring disease progression. We developed the Lémann Index and assessed its ability to measure cumulative structural bowel damage in patients with Crohn's disease (CD). Methods: We performed a prospective, multicenter, international, cross-sectional study of patients with CD evaluated at 24 centers in 15 countries. Inclusions were stratified based on CD location and duration. All patients underwent clinical examination and abdominal magnetic resonance imaging analyses. Upper endoscopy, colonoscopy, and pelvic magnetic resonance imaging analyses were performed according to suspected disease locations. The digestive tract was divided into 4 organs and subsequently into segments. For each segment, investigators collected information on previous operations, predefined strictures, and/or penetrating lesions of maximal severity (grades 1-3), and then provided damage evaluations ranging from 0.0 (no lesion) to 10.0 (complete resection). Overall level of organ damage was calculated from the average of segmental damage. Investigators provided a global damage evaluation (from 0.0 to 10.0) using calculated organ damage evaluations. Predicted organ indexes and Lémann Index were constructed using a multiple linear mixed model, showing the best fit with investigator organ and global damage evaluations, respectively. An internal cross-validation was performed using bootstrap methods. Results: Data from 138 patients (24, 115, 92, and 59 with upper tract, small bowel, colon/rectum, and anus CD location, respectively) were analyzed. According to validation, the unbiased correlation coefficients between predicted indexes and investigator damage evaluations were 0.85, 0.98, 0.90, 0.82 for upper tract, small bowel, colon/rectum, anus, respectively, and 0.84 overall. Conclusions: In a cross-sectional study, we assessed the ability of the Lémann Index to measure cumulative structural bowel damage in patients with CD. Provided further successful validation and good sensitivity to change, the index should be used to evaluate progression of CD and efficacy of treatment.
    Gastroenterology 09/2014; 148(1). DOI:10.1053/j.gastro.2014.09.015 · 16.72 Impact Factor
  • Yize R Wang · John R Cangemi · Edward V Loftus Jr · Michael FF Picco
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    ABSTRACT: Background: Patients with longstanding inflammatory bowel disease (IBD) involving large intestine proximal to rectum are considered to be at increased risk for colorectal cancer (CRC). One prior study showed low utilization of surveillance colonoscopy in patients with ≥8 years of ulcerative colitis (UC) in the USA. Aims: To study use of surveillance colonoscopy among Medicare beneficiaries with IBD in the 2-year period prior to CRC diagnosis. Data and Methods: Our study sample included Medicare beneficiaries in the SEER-Medicare-linked database who were diagnosed with CRC during 2001-2005 and had ≥3 physician visits with ICD-9 diagnosis code for IBD prior to CRC diagnosis. Medicare beneficiaries aged >85 years without Part B coverage or enrolled in HMOs were excluded. Colonoscopy performed within 6-30 months prior to CRC diagnosis was defined as surveillance colonoscopy. The χ(2) test and multivariate logistic regression were used in statistical analysis. Results: Of 241 Medicare beneficiaries with IBD and diagnosed with CRC, 92 (38%) patients underwent ≥1 surveillance colonoscopy in the 2 years prior to cancer diagnosis. The use of surveillance colonoscopy was similar between Crohn's disease (28/86, 33%) and UC (64/155, 41%). In multivariate logistic regression, older age (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94-0.99) was negative associated with surveillance colonoscopy use and personal history of colon polyp (OR 2.73, 95% CI 1.09-6.87) was positively associated with surveillance colonoscopy use. Conclusions: Use of surveillance colonoscopy was low among Medicare beneficiaries with IBD in the 2 years prior to CRC diagnosis. © 2014 S. Karger AG, Basel.
    Digestion 09/2014; 90(1):58-62. DOI:10.1159/000363053 · 2.10 Impact Factor
  • Edward V. Loftus Jr
    Gastroenterology Clinics of North America 09/2014; 43(3):xv–xvii. DOI:10.1016/j.gtc.2014.06.001 · 2.82 Impact Factor
  • Susan C. Abraham · Melissa W. Taggart · Edward V. Loftus Jr · Tsung-Teh Wu
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    ABSTRACT: Inflammatory and reactive conditions are known to mimic dysplasia or malignancy in the gastrointestinal tract. Epithelial atypia that closely mimics low or high grade dysplasia can sometimes be seen in ischemic bowel. To study this phenomenon, we evaluated surgical resections for ischemic enteritis (n = 65) and ischemic colitis (n = 99) that included sections of viable epithelium adjacent to necrosis. Viable epithelium was classified as normal, obviously reactive, low grade dysplasia (LGD)-like atypia, or high grade dysplasia (HGD)-like atypia. Cases with available paraffin blocks were characterized immunohistochemically with antibodies to p16, p53, and MIB-1. Fourteen dysplastic lesions in chronic ulcerative colitis (CUC) served as controls. Dysplasia-like atypia was found in 13 (20%) small bowel resections and 15 (15%) colectomies, most common near re-epithelializing erosions. Two colectomies had extensive dysplasia-like atypia, whereas the other 26 demonstrated focal or several foci of atypia. Nine cases contained HGD-like atypia, 15 contained LGD-like atypia, and 4 showed both HGD- and LGD-like atypia. Features indicating subacute-to-chronic ischemia were more frequent in LGD-like atypia (13/15, 87%) than HGD-like atypia (2/9, 22%, P = 0.003). Dysplasia-like atypia showed overexpression of p16 (73%), p53 (50%), and MIB-1 (92%), but these markers did not reliably distinguish dysplasia-like atypia from true dysplasia in CUC (P = 0.45 for p16, 0.51 for p53, 0.08 for MIB-1). These results underscore the frequency of dysplasia-like atypia in ischemic bowel, which can occasionally be an extensive and worrisome finding. Distinction from true dysplasia requires recognizing the context of the epithelial atypia, since cell-cycle markers were not helpful in classifying individual cases.
    Human pathology 07/2014; 45(7). DOI:10.1016/j.humpath.2014.03.009 · 2.77 Impact Factor
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    ABSTRACT: Background & Aims: Thiopurine therapy for inflammatory bowel disease (IBD) has been associated with increased risk for lymphoma. We estimated the relative risk (RR) of lymphoma in patients with IBD exposed to thiopurines, and compared RR values derived from population-based studies with those from referral center-based studies. We investigated whether active use increased risk compared with past use, and whether sex, age, or duration of use affects risk of lymphoma. Methods We searched MEDLINE, EMBASE, and Cochrane databases, as well as conference abstracts and international publications, for the terms 6-MP and lymphoma, 6-mercaptopurine and lymphoma, thiopurines and lymphoma, azathioprine and cancer and IBD, azathioprine and malignancy and IBD, azathioprine and lymphoma, and lymphoproliferative and thiopurines. Pooled standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were estimated. The deviance statistic from Poisson models was used to calculate heterogeneity. Results Eighteen studies (among 4383 citations) met our inclusion criteria. Overall, the SIR for lymphoma was 4.49 (95% CI, 2.81–7.17), ranging from 2.43 (95% CI, 1.50–3.92) in 8 population studies to 9.16 (95% CI, 5.03–16.7) in 10 referral studies. Population studies demonstrated an increased risk among current users (SIR=5.71; 95% CI, 3.72–10.1) but not former users (SIR=1.42; 95% CI, 0.86–2.34). Level of risk became significant after 1 year of exposure. Men have a greater risk than women (RR=2.05; P<.05); both sexes were at increased risk for lymphoma (SIR for men=3.60; 95% CI, 2.68–4.83 and SIR for women=1.76, 95% CI, 1.08–2.87). Patients younger than 30 years had the highest RR (SIR=6.99; CI, 2.99–16.4); younger men had the highest risk. The absolute risk was highest in patients older than 50 years (1:377 cases per patient–year). Conclusion Compared with studies from referral centers, population-based studies of IBD patients show a lower but significantly increased risk of lymphoma among patients taking thiopurines. The increased risk does not appear to persist after discontinuation of therapy. The risks of lymphoma and potential benefits of therapy should be considered for all patients with IBD.
    Clinical Gastroenterology and Hepatology 05/2014; 13(5). DOI:10.1016/j.cgh.2014.05.015 · 7.90 Impact Factor
  • Yize R Wang · Edward V Loftus Jr · John R Cangemi · Michael F Picco
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    ABSTRACT: Background: The magnitude of racial/ethnic and regional differences in the prevalence of inflammatory bowel disease (IBD) in the United States remains largely unknown. Aims: To estimate differences in the prevalence of IBD by race/ethnicity and region. Methods: The Medical Expenditure Panel Survey, a nationally representative survey of US households and medical conditions, was used. A multivariate logistic model was used in statistical analysis. Results: Among 202,468 individuals surveyed during 1996-2007, 316 were diagnosed with IBD (26 Blacks, 21 Hispanics, and 5 Asians). The prevalence of IBD was higher in Whites [Crohn's disease: 154; ulcerative colitis (UC): 89] than Blacks (Crohn's disease: 68; UC: 25), Hispanics (Crohn's disease: 15; UC: 35), and Asians (Crohn's: 45; UC: 40) (all p < 0.05, except for UC in Asians). The differences in Crohn's disease between Whites and minorities and the difference in UC between Whites and Blacks remained significant in multivariate analysis. In multivariate analysis, there was no regional difference in the prevalence of Crohn's disease, but the prevalence of UC was higher in the Northeast than the South (p < 0.05). Conclusions: There were significant racial/ethnic differences in the prevalence of IBD in the USA. The underlying etiology of these differences warrants additional research.
    Digestion 06/2013; 88(1):20-25. DOI:10.1159/000350759 · 2.10 Impact Factor
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    ABSTRACT: Background:Adalimumab is indicated for the treatment of moderately to severely active Crohn's disease (CD). A systematic analysis of risks and benefits of adalimumab versus traditional non-biologic therapies for patients refractory to non-biologic therapy is lacking.Methods:A base-case analysis compared expected benefits of adalimumab therapy with a 12-week stopping rule for non-responders versus non-biologic therapies using data from clinical trials (CHARM, CLASSIC I). Adverse events (AEs) recorded in clinical trials (CHARM, CLASSIC I, CLASSIC II, GAIN, open-label extensions) were compiled. Sensitivity analyses incorporated all observed benefits of adalimumab and placebo (CHARM, CLASSIC I, GAIN) and observed AEs from a systematic literature review of non-biologic therapies (MEDLINE search of randomized trials 1990–2007). Distributional information from maintenance clinical trial observations and benefit model predictions were used in a probabilistic simulation. Incremental net benefits were estimated based on utility estimates from the literature.Results:Average time in remission (i.e., CDAI <150) over 1 year of therapy was 39.9% for adalimumab versus 6.6% for traditional non-biologic therapies. Adalimumab was associated with fewer expected hospitalizations, better fistula closure rates, and lower AE rates. These findings were robust in sensitivity analyses. In the probabilistic simulation, with serious AEs as a composite of risks, adalimumab provided greater benefits with fewer AEs versus non-biologic therapies (P < 0.01). Adalimumab demonstrated greater incremental net quality-adjusted life-years (0.12) versus non-biologic therapies.Conclusions:Adalimumab demonstrated greater benefits and lower rates of AEs versus traditional non-biologic therapies for patients with moderately to severely active CD who were refractory to non-biologic therapies. (Inflamm Bowel Dis 2011;)
    Inflammatory Bowel Diseases 01/2011; 17(1):127 - 140. DOI:10.1002/ibd.21341 · 4.46 Impact Factor
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    ABSTRACT: Background: Microscopic colitis is a common cause of chronic watery diarrhea of unknown origin. Some patients develop diarrhea after cholecystectomy, and some patients with microscopic colitis have evidence of bile acid malabsorption. However, the association between cholecystectomy and microscopic colitis has not been studied. A protective effect of appendectomy on the development of ulcerative colitis also has been reported, but its relationship with microscopic colitis has not been studied. The aim of this study was to assess cholecystectomy and appendectomy as potential risk factors for the development of microscopic colitis in a nested case-control study. Materials and Methods: Using the Rochester Epidemiology Project, we identified all Olmsted County (Minnesota) residents with an initial diagnosis of microscopic colitis between January 1, 1985, and December 31, 2001. Rates of antecedent cholecystectomy or appendectomy in patients with microscopic colitis were compared with age-, gender-, and calendar year-matched community controls through conditional logistic regression. Results: Microscopic colitis was identified in 130 cases. Cholecystectomy preceded the diagnosis of microscopic colitis in 12 cases (9%) compared with 17 (13%) in the control group (odds ratio [OR] 0.7; 95% CI 0.3–1.5). Appendectomy preceded the diagnosis of microscopic colitis in 39 subjects (30%) compared with 28 (22%) in the control group (OR 1.6; 95% CI 0.9–2.7). Similar results were obtained when the analysis was restricted to microscopic colitis subtype (lymphocytic colitis or collagenous colitis). Conclusions: In this population-based nested case-control study, no significant association was seen between cholecystectomy or appendectomy and the development of microscopic colitis or its subtypes.
    Inflammatory Bowel Diseases 07/2006; 12(8):708 - 711. DOI:10.1097/00054725-200608000-00006 · 4.46 Impact Factor
  • Gastroenterology 04/2003; 124(4). DOI:10.1016/S0016-5085(03)82635-5 · 16.72 Impact Factor
  • Gastroenterology 04/2003; 124(4). DOI:10.1016/S0016-5085(03)80177-4 · 16.72 Impact Factor
  • Gastroenterology 04/2003; 124(4). DOI:10.1016/S0016-5085(03)80035-5 · 16.72 Impact Factor
  • Gastroenterology 04/2003; 124(4). DOI:10.1016/S0016-5085(03)80946-0 · 16.72 Impact Factor
  • Gastroenterology 04/2003; 124(4). DOI:10.1016/S0016-5085(03)82649-5 · 16.72 Impact Factor
  • Gastroenterology 04/2003; 124(4). DOI:10.1016/S0016-5085(03)82625-2 · 16.72 Impact Factor
  • Gastroenterology 04/2001; 120(5). DOI:10.1016/S0016-5085(08)82216-0 · 16.72 Impact Factor
  • Gastroenterology 04/2001; 120(5). DOI:10.1016/S0016-5085(08)80695-6 · 16.72 Impact Factor
  • Edward V. Loftus Jr