William J. Tremaine

Crohn's disease in Olmsted County, Minnesota, 1940–1993: Incidence, prevalence, and survival

BACKGROUND & AIMS Many centers worldwide have reported an increased incidence of Crohns disease, but population-based data in North America are sparse. We studied the incidence and prevalence of Crohns disease in Olmsted County, Minnesota, and examined temporal trends in incidence and survival. METHODS Residents diagnosed with Crohns disease between 1970 and 1993 were incidence cases, and residents with Crohns disease who were alive on January 1, 1991, were prevalence cases. Cases from previous studies were reconfirmed. Rates were adjusted using 1990 U.S. Census figures for whites. Incidence trends were evaluated with a Poisson regression model. Survival from diagnosis was compared with that expected for U.S. north-central whites. RESULTS Between 1940 and 1993, 225 incidence cases were identified, for an adjusted incidence rate of 5.8 per 100,000 person-years. On January 1, 1991, there were 145 residents with Crohns disease, an adjusted prevalence rate of 133 per 100,000, 46% higher than that seen in 1980. Incidence rates before 1964 were significantly lower than those of 1989-1993. Observed survival was less than expected (P = 0.007). CONCLUSIONS The incidence of Crohns disease has stabilized since the 1970s at a rate higher than that seen previously. Prevalence has increased by 46% since 1980. Overall survival is slightly decreased.

Update on the incidence and prevalence of Crohn's disease and ulcerative colitis in Olmsted County, Minnesota, 1940-2000.

Background We previously reported that the prevalence of Crohns disease (CD) and ulcerative colitis (UC) in Olmsted County, Minnesota, had risen significantly between 1940 and 1993. We sought to update the incidence and prevalence of these conditions in our region through 2000. Methods The Rochester Epidemiology Project allows population‐based studies of disease in county residents. CD and UC were defined by previously used criteria. County residents newly diagnosed between 1990 and 2000 were identified as incidence cases, and persons with these conditions alive and residing in the county on January 1, 2001, were identified as prevalence cases. All rates were adjusted to 2000 US Census figures for whites. Results In 1990–2000 the adjusted annual incidence rates for UC and CD were 8.8 cases per 100,000 (95% confidence interval [CI], 7.2–10.5) and 7.9 per 100,000 (95% CI, 6.3–9.5), respectively, not significantly different from rates observed in 1970–1979. On January 1, 2001, there were 220 residents with CD, for an adjusted prevalence of 174 per 100,000 (95% CI, 151–197), and 269 residents with UC, for an adjusted prevalence of 214 per 100,000 (95% CI, 188–240). Conclusion Although incidence rates of CD and UC increased after 1940, they have remained stable over the past 30 years. Since 1991 the prevalence of UC decreased by 7%, and the prevalence of CD increased about 31%. Extrapolating these figures to US Census data, there were ≈1.1 million people with inflammatory bowel disease in the US in 2000. (Inflamm Bowel Dis 2007)

PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis

Background: Inflammatory bowel disease associated with primary sclerosing cholangitis (PSC-IBD) may have a high prevalence of rectal sparing, backwash ileitis, and colorectal neoplasia. Aims: To describe the clinical features and outcomes of PSC-IBD and compare these to a group of chronic ulcerative colitis (CUC) patients. Methods: The medical records of all patients with PSC-IBD evaluated at the Mayo Clinic Rochester between 1987 and 1992 were abstracted for information on endoscopic and histological features, colorectal neoplasia, surgery, and other clinical outcomes. Patients referred for colorectal neoplasia and those who did not undergo colonoscopy with biopsies were excluded. A control group of CUC patients matched for sex, duration of IBD at first clinic visit, and calendar year of first clinic visit was identified, and similar information was abstracted. Results: Seventy one PSC-IBD patients and 142 CUC patients without PSC were identified. Rectal sparing and backwash ileitis were more common in the PSC-IBD group (52% and 51%, respectively) than in controls (6% and 7%, respectively). Overall, colorectal neoplasia developed in 18 cases and 15 controls, including 11 cancers (seven cases and four controls). An increased risk of colorectal neoplasia or death was not detected in a matched analysis. Although the cumulative incidence of colorectal neoplasia was higher in cases (33%) than in controls (13%) at five years, this was of borderline statistical significance (p = 0.054, unmatched log rank test). Overall survival from first clinic visit was significantly worse among cases (79% v 97%) at five years (p<0.001, unmatched log rank test). Conclusion: PSC-IBD is frequently characterised by rectal sparing and backwash ileitis. Colorectal neoplasia develops in a substantial fraction and overall survival is worse. PSC-IBD may represent a distinct IBD phenotype.

Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC), present in 5% of patients with ulcerative colitis, may be associated with pouchitis after ileal pouch-anal anastomosis. The cumulative frequency of pouchitis in patients with and without PSC who underwent ileal pouch-anal anastomosis for ulcerative colitis was determined. A total of 1097 patients who had an ileal pouch-anal anastomosis for ulcerative colitis, 54 with associated PSC, were studied. Pouchitis was defined by clinical criteria in all patients and by clinical, endoscopic, and histological criteria in 83% of PSC patients and 85% of their matched controls. PSC was defined by clinical, radiological, and pathological findings. One or more episodes of pouchitis occurred in 32% of patients without PSC and 63% of patients with PSC. The cumulative risk of pouchitis at one, two, five, and 10 years after ileal pouch-anal anastomosis was 15.5%, 22.5%, 36%, and 45.5% for the patients without PSC and 22%, 43%, 61%, and 79% for the patients with PSC. In the PSC group, the risk of pouchitis was not related to the severity of liver disease. In conclusion, the strong correlation between PSC and pouchitis suggest a common link in their pathogenesis.

Correlation of C-Reactive Protein With Clinical, Endoscopic, Histologic, and Radiographic Activity in Inflammatory Bowel Disease

Introduction: We sought to examine the relationship between C‐reactive protein (CRP) and clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease (IBD). Methods: All IBD patients at our institution between January 2002 and August 2003 who had a CRP, colonoscopy, and either small bowel follow‐through (SBFT) or CT enterography (CTE) performed within 14 days were identified. Clinical activity was assessed retrospectively through review of the medical record. Logistic regression was used in Crohns disease (CD) patients to estimate the odds ratio (OR) with 95% confidence intervals for an elevated CRP. Associations were assessed using Fisher exact test in ulcerative colitis (UC) patients due to small sample size. Results: One‐hundred four CD patients (46% males) and 43 UC and indeterminate colitis patients (44% males) were identified. In CD patients, moderate‐severe clinical activity (OR, 4.5; 95% CI, 1.1‐18.3), active disease at colonoscopy (OR, 3.5; 95% CI, 1.4‐8.9), and histologically severe inflammation (OR, 10.6; 95% CI; 1.1‐104) were all significantly associated with CRP elevation. Abnormal small bowel radiographic imaging was not significantly associated with CRP elevation. In UC patients, CRP elevation was significantly associated with severe clinical activity, elevation in sedimentation rate, anemia, hypoalbuminemia, and active disease at ileocolonoscopy, but not with histologic inflammation. Conclusions: CRP elevation in IBD patients is associated with clinical disease activity, endoscopic inflammation, severely active histologic inflammation (in CD patients), and several other biomarkers of inflammation, but not with radiographic activity.

Ulcerative colitis in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival

BACKGROUND There is significant geographic variation in the reported incidence of ulcerative colitis. AIMS To update the incidence and prevalence of ulcerative colitis in Olmsted County, Minnesota, examine temporal trends, and determine overall survival. PATIENTS All Olmsted County residents diagnosed with ulcerative colitis between 1940 and 1993 (incidence cases), and all residents with ulcerative colitis alive on 1 January 1991 (prevalence cases). METHODS Incidence and prevalence rates were adjusted using 1990 US census figures for whites. The effects of age, sex, and calendar year on incidence rates were evaluated using Poisson regression. Survival from diagnosis was compared with that expected for US north-central whites. RESULTS Between 1940 and 1993, 278 incidence cases were identified, for an adjusted incidence rate of 7.6 cases per 100 000 person years (95% confidence interval (CI), 6.7 to 8.5). On 1 January 1991, there were 218 residents with definite or probable ulcerative colitis, for an adjusted prevalence rate of 229 cases per 100 000 (95% CI, 198 to 260). Increased incidence rates were associated with later calendar years (p<0.002), younger age (p<0.0001), urban residence (p<0.0001), and male sex (p<0.003). Overall survival was similar to that expected (p>0.2). CONCLUSIONS The overall incidence rate of ulcerative colitis in Olmsted County increased until the 1970s, and remained stable thereafter. Incidence rates among men and urban residents were significantly higher. The prevalence rate in Rochester in 1991 was 19% higher than that in 1980. Overall survival was similar to that of the general population.

Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: A pilot study

We report the experience of 11 patients (of 60 planned patients) enrolled in a double-blind, placebo-controlled clinical trial of infliximab in patients with severe, active steroid-refractory ulcerative colitis. The study was terminated prematurely because of slow enrollment. Patients having active disease for at least 2 weeks and receiving at least 5 days of intravenous corticosteroids were eligible to receive a single intravenous infusion of infliximab at 5, 10, or 20 mg/kg body weight. The primary endpoint used in this study was treatment failure at 2 weeks after infusion. Treatment failure was defined as 1) unachieved clinical response as defined by a modified Truelove and Witts severity score, 2) increase in corticosteroid dosage, 3) addition of immunosuppressants, 4) colectomy, or 5) death. Safety evaluations included physical examination, clinical chemistry and hematology laboratory tests, and occurrence of adverse experiences. Four of 8 patients (50%) who received infliximab were considered treatment successes at 2 weeks, compared with none of 3 patients who received placebo. Improvement in erythrocyte sedimentation rates and serum concentrations of C-reactive protein and interleukin-6 correlated with the clinical response observed in patients receiving infliximab. Infusion with infliximab produced no significant adverse events. Infliximab was well tolerated and may provide clinical benefit for some patients with steroid-refractory ulcerative colitis.

Clinical course and costs of care for Crohn's disease: Markov model analysis of a population-based cohort

BACKGROUND & AIMS Crohns disease results in substantial morbidity and high use of health services. The aim of this study was to describe the lifetime clinical course and costs of Crohns disease in a 24-year population-based inception cohort of patients with Crohns disease in Olmsted County, Minnesota. METHODS Disease states were defined by medical and surgical treatment. A Markov model analysis calculated time in each disease state and present value of excess lifetime costs in comparison with an age- and sex-matched cohort. RESULTS For a representative patient, projected lifetime costs were

Early Postoperative Complications are not Increased in Patients with Crohn's Disease Treated Perioperatively with Infliximab or Immunosuppressive Therapy

39,906 per patient using median charges and

Infliximab for Crohn’s disease in clinical practice at the Mayo Clinic: the first 100 patients

125,404 using mean charges. There were 29.1 years (63% of total) without medications. There were 12.7 years (27%) on aminosalicylate therapy, generating