Michelle V. Prosberg

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 Crohns 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.

Hospitalisation, surgical and medical recurrence rates in inflammatory bowel disease 2003-2011—A 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 Crohns 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.

The association between the gut microbiota and the inflammatory bowel disease activity: a systematic review and meta-analysis

Abstract Background: The pathogenesis of inflammatory bowel diseases (IBD) involves complex interactions between the microbiome and the immune system. We evaluated the association between the gut microbiota and disease activity in IBD patients. Methods: Systematic review of clinical studies based on a published protocol. Included patients had ulcerative colitis (UC) or Crohn’s disease (CD) classified as active or in remission. We selected bacteria assessed in at least three studies identified through electronic and manual searches (November 2015). Bias control was evaluated with the Newcastle Ottawa scale (NOS). Results of random-effects meta-analyses were presented as mean differences (MD). Results: Three prospective and seven cross-sectional studies (NOS score 6–8) were included. Five studies included patients with CD (231 patients) and eight included patients with UC (392 patients). Compared to patients in remission, patients with active IBD had lower abundance of Clostridium coccoides (MD = −0.49, 95% CI: −0.79 to −0.19), Clostridium leptum (MD = −0.44, 95% CI: −0.74 to −0.14), Faecalibacterium prausnitzii (MD = −0.81, 95% CI: −1.23 to −0.39) and Bifidobacterium (MD = −0.37, 95% CI: −0.56 to −0.17). Subgroup analyses showed a difference in all four bacteria between patients with UC classified as active or in remission. Patients with active CD had fewer C. leptum, F. prausnitzii and Bifidobacterium, but not C. coccoides. Conclusion: This systematic review suggests that dysbiosis may be involved in the activity of IBD and that there may be differences between patients with CD and UC.

Changes in Disease Behaviour and Location in Patients With Crohn’s Disease After Seven Years of Follow-Up: A Danish Population-based Inception Cohort

Background and Aim Crohns disease [CD] is a progressive inflammatory bowel disease that can lead to complications such as strictures or penetrating disease, and ultimately surgery. Few population-based studies have investigated the predictors for disease progression and surgery in CD according to the Montreal classification. We aimed to identify clinical predictors associated with complicated CD in a Danish population-based inception cohort during the biologic era. Methods All incident patients with CD in a well-defined Copenhagen area, between 2003 and 2004, were followed prospectively until 2011. Disease progression was defined as the development of bowel stricture [B2] or penetrating disease [B3] in patients initially diagnosed with non-stricturing/non-penetrating disease [B1]. Associations between disease progression and/or resection, and multiple covariates, were investigated by Cox regression analyses. Results In total, 213 CD patients were followed. A total of 177 [83%] patients had B1 at diagnosis. Patients who changed location had increased risk of disease progression (hazard ratio [HR] = 3.1, 95% CI: 1.12,8.52). Biologic treatment was associated with lower risk of change in location [HR = 0.3, 95% CI: 0.1-0.7]. Colonic involvement [L2 or L3 vs L1] was associated with a lower risk of surgery (HR = 0.34/0.22, 95% CI: [0.13,0.86]/[0.08,0.60]). All CD patients who progressed in behaviour or changed location had an increased risk of surgery [p < 0.05]. Conclusions This population-based inception cohort study demonstrates that changes in disease location or behaviour in patients with CD increase their risk of resection. Our findings highlight the protective effect of biologic treatment with regard to change in disease location, which might ultimately improve the disease course for CD patients.

Systematic review and meta‐analysis: assessment of factors affecting disability in inflammatory bowel disease and the reliability of the inflammatory bowel disease disability index

The Inflammatory Bowel Disease Disability Index (IBD‐DI) has recently been developed for patients with Crohns disease (CD) and ulcerative colitis (UC).

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.