We previously reported the costs associated with surgery for chronic ulcerative colitis in the Olmsted County population and found that direct medical costs after surgery were significantly reduced compared with before surgery. However, in that study costs associated with chronic medical therapy for ulcerative colitis were not assessed in non-surgical patients.
To gain insight into the drivers of costs of treatment for chronic ulcerative colitis, we assessed direct costs after surgical and medical therapy in 120 patients in the Rochester Epidemiology Project database.
A cohort of 60 patients who recovered from surgery for ulcerative colitis from 1988-2006 were 1:1 matched by age, gender, and referent year to medically-managed patients. Direct healthcare costs were estimated from an institutional database, and observed cost differences over a 2-year period were calculated. Statistical significance was assessed by paired t-tests and bootstrapping; mean costs are adjusted 2009 constant dollars.
Two-year direct healthcare costs in the surgical and medical cohorts were $10,328 vs. $6,586 (p=0.19)In the surgical cohort, Brooke ileostomy patients were observed to have higher costs than patients with ileal pouch-anal anastomosis (Δ$8,187, p=0.04), and after ileal pouch, pouchitis was associated with increased costs (Δ$12,763, p<0.01). In the medical cohort, disease extent (Δ$6,059, p=0.04) but not disease severity was associated with increased costs.
Relatively small population size, in county tertiary referral center.
Before the introduction of biologic therapies for ulcerative colitis, patients were observed to have similar healthcare costs after surgical and medical therapy. In medically treated patients, disease extent was associated with increased costs, while in surgically-treated patients, permanent ileostomy and pouchitis were observed to be associated with increased costs.
Chronic ulcerative colitis; Population-based; Direct costs; Surgery ileal pouch-anal anastomosis
Spondyloarthritis is an extraintestinal manifestation of inflammatory bowel disease with important clinical impact, although the frequency is uncertain. We sought to assess the cumulative incidence and clinical spectrum of spondyloarthritis in patients with Crohn’s disease (CD) in a population-based cohort.
The medical records of a population-based cohort of Olmsted County, Minnesota residents diagnosed with CD between 1970 and 2004 were reviewed. Patients were followed longitudinally until migration, death, or December 31, 2010. We used the European Spondyloarthropathy Study Group, Assessment of Spondyloarthritis international Society (ASAS) criteria and modified New York criteria to identify patients with spondyloarthritis. The Kaplan-Meier method was used to estimate the cumulative incidence of spondyloarthritis following CD diagnosis.
The cohort included 311 patients with CD (49.8% females; median age, 29.9 years [range, 8–89]). Thirty-two patients developed spondyloarthritis based on ASAS criteria. The cumulative incidence of spondyloarthritis after CD diagnosis was 6.7% (95% confidence interval, 2.5%–6.7%) at 10 years, 13.9% (8.7%–18.8%) at 20 years, and 18.6% (11.0%–25.5%) at 30 years. The 10-year cumulative incidence of ankylosing spondylitis was 0 while both the 20-year and 30-year cumulative incidences were 0.5% (95% CI, 0–1.6%).
We have for the first time defined the actual cumulative incidence of spondyloarthritis in CD using complete medical record information in a population-based cohort. The cumulative incidence of all forms of spondyloarthritis increased to approximately 19% by 30 years from CD diagnosis. Our results emphasize the importance of maintaining a high level of suspicion for spondyloarthritis when following patients with CD.
Spondyloarthritis; Crohn’s disease; epidemiology; ankylosing spondylitis
Background & Aims
We sought to estimate the need for surgery in an American population-based cohort of Crohn’s disease.
The medical records of 310 incident cases of Crohn’s disease from Olmsted County, Minnesota, diagnosed between 1970 and 2004, were reviewed through March 2009. Cumulative incidence was estimated using the Kaplan-Meier method, and associations between baseline factors and time to first event were assessed using proportional hazards regression and expressed as hazard ratios (HR) with 95% confidence intervals (95% CI).
Median follow-up per patient was 12.0 years. One hundred fifty-two patients underwent at least one major abdominal surgery, 65 had at least two surgeries, and 32 had at least three. The cumulative probability of major abdominal surgery was 38%, 48% and 58% at 5, 10 and 20 years after diagnosis, respectively. Baseline factors significantly associated with time to major abdominal surgery were: ileocolonic (HR, 3.3), small bowel (HR, 3.4) and upper gastrointestinal (HR, 4.0) extent, relative to colonic alone; current cigarette smoking (HR, 1.7), male gender (HR, 1.6), penetrating disease behavior (HR, 2.7), and early corticosteroid use (HR=1.6). Major abdominal surgery rates remained stable, with 5-year cumulative probabilities in 1970–74 and 2000–04 of 37.5% and 35.1%, respectively.
The cumulative probability of major abdominal surgery in this population-based cohort of Crohn’s disease approached 60% after 20 years of disease, and many patients required second or third surgeries. Non-colonic disease extent, current smoking, male gender, penetrating disease behavior, and early steroid use were significantly associated with major abdominal surgery.
Crohn’s disease; surgery; natural history; risk factors
To evaluate the outcomes of corticosteroid-treated microscopic colitis in a population-based cohort, and to compare these outcomes in patients treated with prednisone or budesonide
A historical cohort study of Olmsted County, Minnesota residents diagnosed with collagenous colitis or lymphocytic colitis from 1986 to 2010 was performed using the resources of the Rochester Epidemiology Project.
Of 315 patients, 80 (25.4%) were treated with corticosteroids. The median age was 66.5 years (range: 16 – 95) and 78.7% were female. Forty patients (50%) had lymphocytic colitis and 40 (50%) had collagenous colitis. Six patients were lost to follow-up. The remaining 74 had a median follow-up of 4 years (range: 0.2 – 14); 56 (75.6%) had complete response and 15 (20.3%) had partial response. Fifty patients out of 71 who responded (70.4%) had a recurrence after corticosteroid discontinuation. After 397 person years of follow-up in the 73 patients with long-term data, 47 (64.4%) required maintenance with corticosteroids.
Prednisone was used in 17 patients (21.2%) and budesonide in 63 (78.8%). Patients treated with budesonide had a higher rate of complete response than those treated with prednisone (82.5% vs 52.9%; odds ratio, 4.18; 95% CI, 1.3 – 13.5) and were less likely to recur (hazard ratio, 0.38; 95% CI, 0.18 – 0.85; p=0.02).
Patients with microscopic colitis often respond to corticosteroid therapy, but with a high relapse rate. Budesonide had a higher response rate and a lower risk of recurrence than prednisone.
microscopic colitis; corticosteroid; outcomes; response; recurrence
Mucosal healing is gaining more acceptance as a measure of disease activity in Crohn's disease and ulcerative colitis, and it is also gaining acceptance as an endpoint in clinical trials. Recent publications have correlated achievement of mucosal healing with good outcomes. Currently, there is no validated definition of what constitutes mucosal healing in inflammatory bowel disease. In clinical trials of ulcerative colitis, mucosal healing has been achieved with 5-aminosalicylates, corticosteroids, azathioprine, and infliximab. For Crohn's disease, mucosal healing has been achieved with corticosteroids, infliximab, and adalimumab, and mucosal healing has been maintained with infliximab. Achievement of long-term mucosal healing has been associated with a decreased risk of colectomy and colorectal cancer in ulcerative colitis patients, a decreased need for cortico-steroid treatment in Crohn's disease patients, and a trend toward a decreased need for hospitalization in Crohn's disease patients. Unfortunately, assessment of mucosal healing requires regular use of endoscopy, which is associated with increased costs, patient discomfort, and side effects. Biomarkers such as fecal calprotec-tin, fecal lactoferrin, serum C-reactive protein, and fecal S1 00A1 2 have been shown to correlate with disease activity in ulcerative colitis and Crohn's disease; in the future, these biomarkers might be used as surrogate markers for mucosal healing. Newer clinical trials are incorporating mucosal healing as an endpoint for evaluation of efficacy. However, before mucosal healing will be sufficient to guide therapy, clinicians need a standard definition of mucosal healing and a consistently used, prospectively validated scale with good interobserver agreement.
Mucosal healing; ulcerative colitis; Crohn's disease; anti—tumor necrosis factor agents; corticosteroids; colonoscopy
To determine the association between asthma and proinflammatory conditions.
Participants and Methods
This population-based retrospective matched cohort study enrolled all asthmatic patients among Rochester, Minnesota, residents between January 1, 1964, and December 31, 1983. For each asthmatic patient, 2 age-and sex-matched nonasthmatic individuals were drawn from the same population. The asthmatic and nonasthmatic cohorts were followed forward in the Rochester Epidemiology Project diagnostic index for inflammatory bowel disease (IBD), rheumatoid arthritis (RA), diabetes mellitus (DM), and coronary heart disease (CHD) as outcome events. Data were fitted to Cox proportional hazards models.
We identified 2392 asthmatic patients and 4784 nonasthmatic controls. Of the asthmatic patients, 1356 (57%) were male, and mean age at asthma onset was 15.1 years. Incidence rates of IBD, RA, DM, and CHD in nonasthmatic controls were 32.8, 175.9, 132.0, and 389.7 per 100,000 person-years, respectively; those for asthmatic patients were 41.4, 227.9, 282.6, and 563.7 per 100,000 person-years, respectively. Asthma was associated with increased risks of DM (hazard ratio, 2.11; 95% confidence interval, 1.43-3.13; P<.001) and CHD (hazard ratio, 1.47; 95% confidence interval, 1.05-2.06; P=.02) but not with increased risks of IBD or RA.
Although asthma is a helper T cell type 2–predominant condition, it may increase the risks of helper T cell type 1–polarized proinflammatory conditions, such as CHD and DM. Physicians who care for asthmatic patients need to address these unrecognized risks in asthmatic patients.
CHD, coronary heart disease; CI, confidence interval; DM, diabetes mellitus; HR, hazard ratio; IBD, inflammatory bowel disease; ICD, International Classification of Diseases; RA, rheumatoid arthritis; REP, Rochester Epidemiology Project; TH, helper T cell
Although the epidemiology of microscopic colitis has been described in Europe, no such data exist from North America. We studied the incidence, prevalence and temporal trends of microscopic colitis in a geographically defined US population.
Design and setting
In this population based cohort study, residents of Olmsted County, Minnesota, with a new diagnosis of microscopic colitis, and all who had colon biopsies for evaluation of diarrhoea, between 1 January 1985 and 31 December 2001 were identified. Biopsies were reviewed for confirmation (cases) and to identify missed cases (diarrhoea biopsies).
Main outcome measures
Incidence rates, age and sex adjusted to the 2000 US white population. Poisson regression assessed the association of calendar period, age and sex with incidence.
We identified 130 incident cases for an overall rate of 8.6 cases per 100 000 person‐years. There was a significant secular trend, with incidence increasing from 1.1 per 100 000 early in the study to 19.6 per 100 000 by the end (p<0.001). Rates increased with age (p<0.001). By subtype, the incidence was 3.1 per 100 000 for collagenous colitis and 5.5 per 100 000 for lymphocytic colitis. Collagenous colitis was associated with female sex (p<0.001) but lymphocytic colitis was not. Prevalence (per 100 000 persons) on 31 December 2001 was 103.0 (39.3 for collagenous colitis and 63.7 for lymphocytic colitis).
The incidence of microscopic colitis has increased significantly over time, and by the end of the study, the incidence and prevalence were significantly higher than reported previously. Microscopic colitis is associated with older age, and collagenous colitis is associated with female sex.
Background and aims
The cumulative incidence of and risk factors for perianal Crohn’s disease for findings other than fistulas are unknown.
The medical records of 310 incident cases of Crohn’s disease from Olmsted County, Minnesota, diagnosed between 1970 and 2004, were reviewed for evidence of perianal disease findings other than fistulas. Cumulative incidence was estimated using the Kaplan-Meier method, and associations between baseline factors and time to first event were assessed using proportional hazards regression. Four types of lesions were studied: anorectal strictures, deep anal canal ulcers, anal fissures, and perianal skin tags.
The 10-year cumulative probability from time of diagnosis was 5.8% (95% confidence interval [CI], 2.6%-8.8%) for anorectal strictures, 6.6% (3.6%-9.6%) for deep anal canal ulcers, 10.5% (6.8%-14.1%) for anal fissures, and 18.7% (13.9%-23.3%) for perianal skin tags. The cumulative probability for any perianal lesion other than fistulas was 21.3% (16.5%-25.8%) at 5 years and 29.2% (23.5%-34.5%) at 10 years. Baseline factors associated with time to first perianal lesion other than fistulas were age (hazard ratio [HR] per 10 years, 0.9; 95% CI, 0.8-0.98; p=0.026), female gender (HR, 1.7; 95% CI, 1.1-2.7; p=0.013), and presence of extraintestinal manifestations (HR, 1.7; 95% CI, 1.03-2.8; p=0.038).
Perianal lesions other than fistulas occurred frequently during the clinical course of Crohn’s disease. Female gender and extraintestinal manifestations were associated with increased risks for perianal lesions other than fistulas, while older age at diagnosis was associated with a slightly decreased risk.
Crohn’s disease; natural history; anorectal strictures; anal ulcers; perianal tags; anal fissures
To evaluate open-label adalimumab therapy for clinical effectiveness, fistula healing, patient-reported outcomes and safety in Canadian patients with moderate to severe Crohn’s disease (CD) who were either naive to or previously exposed to antitumour necrosis factor (anti-TNF) therapy.
Patients with moderate to severe CD (CD activity index [CDAI] score of greater than 220, or Harvey-Bradshaw index [HBI] of 7 or greater) were eligible. Patients received open-label adalimumab as induction (160 mg and 80 mg subcutaneously [sc]) at weeks 0 and 2, respectively and maintenance (40 mg sc every other week) therapy. At or after eight weeks, patients with flare or nonresponse could have their dosage increased to 40 mg sc weekly. Patients were followed for a minimum of six months or until adalimumab was commercially available in Canada.
Of the 304 patients enrolled, 160 were infliximab experienced, while 144 were anti-TNF naive. HBI remission (HBI score of 4 or lower) at week 24 was achieved by 53% of anti-TNF-naive and 36% of infliximab-experienced patients (P<0.01; P<0.001 for both groups for all visits versus baseline). Fistula healing rates at week 12 were 48% for anti-TNF-naive patients, and 26% for infliximab-experienced patients. At week 24, fistula healing rates were significantly greater for the anti-TNF-naive group (60% versus 28%; P<0.01). Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients. Serious infections occurred in 2% of patients.
Adalimumab therapy induced and sustained steroid-free remission in both infliximab-experienced and anti-TNF-naive patients with moderate to severe CD. Clinically meaningful rates of fistula healing were also observed. Improvements in patient-reported outcomes were sustained throughout the 24-week study period.
Adalimumab; Crohn’s disease; Fistula; Quality of life; Steroid-free remission; Work productivity
Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are chronic conditions affecting millions of individuals in the United States. The symptoms are well-documented and can be debilitating. How these chronic gastrointestinal (GI) conditions impact the daily lives of those afflicted is not well documented, especially from a patient's perspective.
Here we describe data from a series of 22 focus groups held at three different academic medical centers with individuals suffering from chronic GI conditions. All focus groups were audio recorded and transcribed. Two research team members independently analyzed transcripts from each focus group following an agreed upon coding scheme.
One-hundred-thirty-six individuals participated in our study, all with a chronic GI related condition. They candidly discussed three broad themes that characterize their daily lives: identification of disease and personal identity, medications and therapeutics, and daily adaptations. These all tie to our participants trying to deal with symptoms on a daily basis. We find that a recurrent topic underlying these themes is the dichotomy of experiencing uncertainty and striving for control.
Study participants' open dialogue and exchange of experiences living with a chronic GI condition provide insight into how these conditions shape day-to-day activities. Our findings provide fertile ground for discussions about how clinicians might best facilitate, acknowledge, and elicit patients' stories in routine care to better address their experience of illness.
Chronic gastrointestinal conditions; Inflammatory Bowel Disease; Irritable Bowel Syndrome; Patient adaptation; Symptom experience
Background & Aims
A few cross-sectional studies reported an increased risk of inflammatory bowel disease (IBD) among asthmatics. We conducted a population-based case-control study that applied predetermined criteria for asthma and IBD to determine whether asthma, as a T-helper 2 (Th2) condition, reduces the risk of IBD a Th1 condition.
This was a population-based case-control study using criteria-based ascertainment for IBD and asthma. Subjects were all Rochester, Minnesota, residents who had developed IBD between 1964 and 1983 and their age-and gender-matched controls, using 1:1 matching. Controls were randomly selected from the community using the Rochester Epidemiology Project database and confirmed not to have IBD. All cases and controls were merged with the database comprising all Rochester residents with or without asthma between 1964 and 1983.
Of the 231 IBD cases, 55% had ulcerative colitis and the remainder had Crohn’s disease. Of these, 50.4% were male and 98.1% were Caucasians. The mean age at the time of IBD diagnosis was 33.8 years. Four cases (1.7%) had asthma prior to index date of IBD, whereas two controls (0.9%) had asthma (unadjusted odds ratio: 3.0, 95% CI: 0.31–28.84, P=0.34). Similarly, 16 IBD cases (6.9%) had asthma ever while 12 controls (5.2%) had asthma ever (unadjusted odds ratio: 1.4, 95% CI: 0.62–3.38, p=0.40).
Asthma as a Th2 condition does not reduce the risk of IBD as a Th1 condition. Because of the limitations of our study and others, the association between asthma and IBD needs to be further studied.
Asthma; inflammatory bowel disease; epidemiology; risk; ulcerative colitis; Crohn’s disease; Rochester Epidemiology Project; case-control study
Background and Aims
We sought to assess the evolution of Crohn's disease behavior in an American population-based cohort.
The medical records of all Olmsted County, Minnesota residents who were diagnosed with Crohn's disease from 1970 to 2004 were evaluated for their initial clinical phenotype, based on the Montreal classification. The cumulative probabilities of developing structuring and/or penetrating complications were estimated using the Kaplan-Meier method. Proportional hazards regression was used to assess associations between baseline risk factors and changes in behavior.
Among 306 patients, 56.2% were diagnosed between the ages of 17 and 40 years. Disease extent was ileal in 45.1%, colonic in 32.0%, and ileocolonic in 18.6%. At baseline, 81.4% had non-stricturing non-penetrating disease, 4.6% had stricturing disease, and 14.0% had penetrating disease. The cumulative risk of developing either complication was 18.6% at 90 days, 22.0% at 1 year, 33.7% at 5 years, and 50.8% at 20 years after diagnosis. Among 249 patients with non-stricturing, non-penetrating disease at baseline, 66 changed their behavior after the first 90 days from diagnosis. Relative to colonic extent, ileal, ileocolonic, and upper gastrointestinal extent were significantly associated with changes in behavior, whereas the association with perianal disease was barely significant.
In a population-based cohort study, 18.6% of patients with Crohn's disease experienced penetrating or stricturing complications within 90 days after diagnosis; 50% experienced intestinal complications 20 years after diagnosis. Factors associated with development of complications were the presence of ileal involvement and perianal disease.
Crohn's disease; complications; stricture; fistula; abscess; natural history
We hypothesized that patients undergoing definitive surgery for chronic ulcerative colitis have reduced direct medical costs after, as compared with before, total proctocolectomy.
A population-based cohort who underwent proctocolectomy for ulcerative colitis from 1988–2007 was identified using the Rochester Epidemiology Project. Total direct healthcare costs were estimated from an administrative database. The primary outcome was the observed cost difference between a 2-year period before surgery and the 2-year period after a surgery/recovery period (surgery+180 days). Statistical significance was assessed using paired t-tests and bootstrapping methods. Demographic data were presented as median (interquartile range) or frequency (proportion). Mean costs are reported in 2007 constant dollars.
Sixty patients were Olmsted County, Minnesota residents at operation and for the entire period of obervation. Overall 40 patients (66%) were men, median age of 42 years (31–52), median colitis duration of 4 years (1–11). Operations included ileal-pouch anal anastomosis (n=45, mean cost of surgery/recovery period $50,530) or total proctocolectomy with Brooke ileostomy (n=15, mean cost of surgery/recovery period $39,309). In the pouch subgroup, direct medical costs on average were reduced by $9,296 (P<0.001, bootstrapped 95% CI: $324 to $15,628) in the 2-years after recovery. In the Brooke ileostomy subgroup, direct medical costs on average were reduced by $12,529 (P<0.001, bootstrapped 95% CI: $6467 to $18,688) in the 2-years after recovery.
Surgery for chronic ulcerative colitis resulted in reduced direct costs in the 2-years after surgical recovery. These observations suggest that surgical intervention for ulcerative colitis is associated with long-term economic benefit.
cost analysis; ulcerative colitis; proctocolectomy; ileal pouch-anal anastomosis; population-based; epidemiology
For diagnosis, assessing disease activity, complications and extraintestinal manifestations, and monitoring response to therapy, patients with inflammatory bowel disease undergo many radiological studies employing ionizing radiation. However, the extent of radiation exposure in these patients is unknown.
A population-based inception cohort of 215 patients with inflammatory bowel disease from Olmsted County, Minnesota, diagnosed between 1990 and 2001, was identified. The total effective dose of diagnostic ionizing radiation was estimated for each patient. Linear regression was used to assess the median total effective dose since symptom onset.
The number of patients with Crohn's disease and ulcerative colitis was 103 and 112, with a mean age at diagnosis of 38.6 and 39.4 yr, respectively. Mean follow-up was 8.9 yr for Crohn's disease and 9.0 yr for ulcerative colitis. Median total effective dose for Crohn's disease was 26.6 millisieverts (mSv) (range, 0–279) versus 10.5 mSv (range, 0–251) for ulcerative colitis (P < 0.001). Computed tomography accounted for 51% and 40% of total effective dose, respectively. Patients with Crohn's disease had 2.46 times higher total effective dose than ulcerative colitis patients (P = 0.001), adjusting for duration of disease.
Annualizing our data, the radiation exposure in the inflammatory bowel disease population was equivalent to the average annual background radiation dose from naturally occurring sources in the U.S. (3.0 mSv). However, a subset of patients had substantially higher doses. The development of imaging management guidelines to minimize radiation dose, dose-reduction techniques in computed tomography, and faster, more robust magnetic resonance techniques are warranted.
Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural damage to the bowel, which may predict long-term disability, is needed. The aim of this article is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohn's disease (IPNIC) group. This instrument, called the Crohn's Disease Digestive Damage Score (the Lémann score), should take into account damage location, severity, extent, progression, and reversibility, as measured by diagnostic imaging modalities and the history of surgical resection. It should not be “diagnostic modality driven”: for each lesion and location, a modality appropriate for the anatomic site (for example: computed tomography or magnetic resonance imaging enterography, and colonoscopy) will be used. A total of 24 centers from 15 countries will be involved in a cross-sectional study, which will include up to 240 patients with stratification according to disease location and duration. At least 120 additional patients will be included in the study to validate the score. The Lémann score is expected to be able to portray a patient's disease course on a double-axis graph, with time as the x-axis, bowel damage severity as the y-axis, and the slope of the line connecting data points as a measure of disease progression. This instrument could be used to assess the effect of various medical therapies on the progression of bowel damage. (Inflamm Bowel Dis 2011)
Crohn's disease; illness index severity; magnetic resonance imaging