Disease course and surgery rates in inflammatory bowel disease: a population-based, 7-year follow-up study in the era of immunomodulating therapy.

OBJECTIVES: In this population-based 7-year follow-up of incident patients with ulcerative colitis (UC) or Crohn's disease (CD), we aimed to describe disease progression and surgery rates in an era influenced by the increased use of immunosuppressants and the introduction of biological therapy. METHODS: From 1 January 2003 to 31 December 2004, all incident cases (562) of patients diagnosed with UC, CD, or inflammatory bowel disease unclassified in a well-defined Copenhagen area were registered. Medical records were reviewed from 1 November 2011 to 30 November 2012, and clinical data were registered. Clinical data on surgery, cancer, and death were cross-checked with register data from national health administrative databases in order to include missed data. RESULTS: In total, 513 patients (213 CD and 300 UC) entered the follow-up study. Twenty-six patients changed diagnosis during the follow-up. Changes in disease localization and behavior in CD according to the Vienna classification were observed in 23.9% and 15.0% of the patients, respectively, during follow-up. In total, 28.3% of the 300 UC patients had disease progression during the follow-up. The overall use of systemic steroids, immunomodulators, and anti-tumor necrosis factor agents in CD was 86.4%, 64.3%, and 23.5%, respectively. The rate of first-time intestinal resection in CD was 29.1% (n=62), and the 7-year cumulative risk was 28.5%. The cumulative risk of colectomy in UC was 12.5% at 7 years. CONCLUSIONS: UC and CD are dynamic diseases that progress in extent and behavior over time. The resection rate in CD and the colectomy rate in UC are still relatively high, although the rates seem to have decreased compared with historic data, which could be due to an increase in the use of immunomodulating therapy.

Probiotic Treatment of Ulcerative Colitis with Trichuris suis ova: A Randomized, Double-blinded, Placebo-controlled Clinical Trial (the PROCTO Trial).

BACKGROUND AND AIMS: To demonstrate that administration of 7500 Trichuris suis ova every second week over 24 weeks would reduce the intestinal inflammation in moderate ulcerative colitis. METHODS: A single-centre, randomized, double-blinded, placebo-controlled, phase 2b clinical trial of 7500 Trichuris suis ova every two weeks for 24 weeks compared to placebo in moderate activity of ulcerative colitis (Mayo score 6-10) were performed. Primary outcome: Clinical remission. Secondary outcomes: Clinical response at 24 weeks, complete corticosteroid-free clinical remission, endoscopic remission, symptomatic remission at 12 and 24 weeks and partial Mayo score over time. RESULTS: 119 patients were randomized to Trichuris suis ova (n=60) and placebo (n=59). At week 24, clinical remission was achieved in 30% of Trichuris suis ova-treated vs. 34% of placebo-treated (RR=0.89; CI:0.52-1.50; p=0.80, ITT). No difference was found in clinical response in any of the clinical response subgroups. However, in patients who did not need treatment with corticosteroids during the trial, a temporary effect of TSO was seen in the analysis of symptomatic remission of week 12 (p=0.01), and the partial Mayo score at week 14 and week 18 (p<0.05 and p=0.02). CONCLUSIONS: Compared to placebo, Trichuris suis ova was not superior in achieving clinical remission at week 24 in ulcerative colitis or in achieving clinical Mayo score reduction, complete corticosteroid-free clinical remission or endoscopic remission. However, Trichuris suis ova treatment induced symptomatic temporary remission at week 12.

Proximal Disease Extension in Patients With Limited Ulcerative Colitis: A Danish Population-based Inception Cohort.

BACKGROUND AND AIMS: Disease extent in ulcerative colitis [UC] is dynamic and can progress over time. Little is known about risk factors for UC extension in the era of biologics. We investigated the risk of UC extension and subsequent risk of surgery in a Danish population-based cohort. METHODS: All incident UC cases in a strictly defined Copenhagen area between 2003 and 2004 were followed prospectively through 2011. Disease extension was defined as patients with limited UC [E1 or E2] at diagnosis having progressed from the initial extent by colonoscopy or surgery to E2 or extensive colitis [E3]. Associations between progression or colectomy and multiple covariates were analysed by Cox regression analysis. RESULTS: Of 300 UC patients, 220 [73%] had E1 or E2 at diagnosis. During follow-up, 50 [23%] patients with E1/E2 progressed to E3, and 22 [10%] with E1 progressed to E2. Disease extent at diagnosis was the sole predictor of extension to E3. A total of 18 [8%] patients with E1/E2 at diagnosis had a colectomy. Progression from E1/E2 to E3, female gender and a history of smoking were risk factors for colectomy. CONCLUSION: After 7 years of follow-up, 33% of patients with limited UC experienced disease extension. Only extent at diagnosis was a clinical predictor for disease extension. The risk of colectomy was increased in former smokers and patients who progressed to extensive colitis. This highlights the need to prevent disease progression in patients with limited UC, and to identify new histological or molecular markers that might help stratify risks for disease progression.

Long-term Compliance with Oral 5-aminosalicylic Acid Therapy and Risk of Disease Recurrence in Patients with Ulcerative Colitis: A Population-based Cohort Study.

BACKGROUND: Noncompliance to long-term medical therapy is a well-known problem among patients treated for ulcerative colitis, but studies of long-term consequences in unselected patients are lacking. The authors aimed to determine the risk of recurrence according to long-term compliance with oral 5-aminosalicylic acid among unselected patients with ulcerative colitis. METHODS: The authors conducted a 7-year follow-up study of a population-based inception cohort of 243 Danish patients with ulcerative colitis diagnosed from 2003 to 2004. Compliance was defined as consumption of ≥80% of prescribed oral 5-aminosalicylic acid. Data were collected from medical records and the Danish National Prescription Database. They performed Cox regression analysis with adjustments for demographic and clinical characteristics to examine risk of recurrence (defined by increased use of oral 5-Aminosalicylic Acid, other additional treatment, or colectomy) in compliant versus noncompliant patients. RESULTS: In total, 182 patients (75%) experienced at least 1 recurrence during follow-up. For the first year after diagnosis, risk of recurrence did not differ significantly between compliant and noncompliant patients. For 1 to 3 years (hazard ratio: 0.46, 95% CI, 0.33-0.63) and 3 to 8 years (hazard ratio: 0.42, 95% CI, 0.32-0.55) after diagnosis, risk of recurrence was significantly decreased among noncompliant patients compared with that of compliant patients. CONCLUSIONS: This unselected cohort study revealed a reverse association between compliance and recurrence of ulcerative colitis. This is unlikely to be explained by severe confounding because the authors were able to adjust for several demographic and clinical factors. Results may instead reflect that patients during recurrence-free periods through self-management choose not to take their medication.

Low Risk of Unemployment, Sick Leave, and Work Disability Among Patients with Inflammatory Bowel Disease: A 7-year Follow-up Study of a Danish Inception Cohort.

BACKGROUND: To assess the occurrence and risk of unemployment (UE), sick leave (SL), and work disability (WD) in incident patients with inflammatory bowel disease (IBD) after 7 years of follow-up compared with the background population and to determine outcome predictors. METHODS: The study population consisted of patients aged 18 to 67 years (N = 379) from an IBD inception cohort registered January 1, 2003 to December 31, 2004 in the Copenhagen area. Clinical data were retrospectively collected from medical records. Data on UE, SL, and WD were retrieved from national registries. A random subset of the general population (n = 1435) were matched with IBD cases based on sex, age, and residency. The cumulative probabilities of UE, SL, and WD were calculated. A Cox proportional hazard regression was performed to identify possible outcome predictors. RESULTS: There was no difference in UE rates between patients with IBD and controls (P = 0.23). The risk of SL was significantly increased in patients with IBD (hazard ratio 2.0; 95% confidence interval 1.7-2.4). Patients with IBD showed a higher risk of WD (hazard ratio 2.1; 95% confidence interval 1.2-3.8), particularly male patients older than 55 years. The rate of WD in CD (5.8%) was markedly lowered compared with previous studies. Within the IBD population, sex, educational level, disease behavior, smoking status, and surgery were predictors of UE, SL, and WD. CONCLUSIONS: The observed increased risk of SL and WD in patients with IBD underscores the need for the early identification of risk factors. A multidisciplinary approach to secure IBD patients' participation in the labor market is recommended.

Hospitalisation, surgical and medical recurrence rates in inflammatory bowel disease 2003-2011­a Danish population-based cohort study.

OBJECTIVE: The aim of this study is to evaluate the cumulative probability of recurrence and admission rates in an inflammatory bowel disease (IBD) inception cohort diagnosed in 2003-2004. METHODS: Data on medications, phenotypes and surgery for 513 individuals with ulcerative colitis (UC, n=300) and Crohn's disease (CD, n=213) were obtained from medical records and linked to population-based health administrative database information. The admission rates and cumulative probability of recurrences were estimated, and the association with the baseline factors and medication was tested. RESULTS: The cumulative risk of first recurrence after 1, 5 and 7 years was 40%, 63%, and 66% in CD patients and 51%, 75%, and 79% in UC patients, respectively. The cumulative risk of first surgical relapse was 6%, 18%, and 23% at 1, 5 and 7 years in CD respectively. One hundred and CD patients (66%) and 142 UC patients (47%) had at least one IBD-related hospitalisation. The hospitalisation rate decreased from 7.0 days/person-year in year one to 0.9 day at year 5 in CD, and from 4.7 days to 0.4 days for UC patients. Age above 40, current smoking, stricturing behaviour, and disease localisation (colonic, ileocolonic, and upper-GI) at diagnosis were predictors of recurrence in CD. In UC, age above 40 and former smoker status were predictors of recurrence and left-sided and extensive colitis were predictors of first-time hospitalisation. CONCLUSION: In an era of improved treatment options, the recurrence rates, but not the surgery or hospitalisation rates, have decreased for CD but not for UC. The phenotypic characteristics at diagnosis predict the risk of recurrence and hospitalisation.