Maurice G. Russel

Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease.

OBJECTIVES:Disease course in inflammatory bowel disease (IBD) is variable and difficult to predict. To optimize prognosis, it is of interest to identify phenotypic characteristics at disease onset and other prognostic factors that predict disease course. The aim of this study was to evaluate such factors in a population-based IBD group.METHODS:IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. A follow-up questionnaire was developed and medical records were reviewed. Patients were classified according to phenotype at diagnosis and risk factors were registered. Disease severity, cumulative medication use, and “surgical” and “nonsurgical” recurrence rates were calculated as outcome parameters.RESULTS:In total, 476 Crohns disease (CD), 630 ulcerative colitis (UC), and 81 indeterminate colitis (IC) patients were diagnosed. In CD (mean follow-up 7.6 years), 50% had undergone resective surgery. In UC (mean follow-up 7 years), colectomy rate was 8.3%. First year cumulative recurrence rates per 100 patient-years for CD, UC, and IC were 53, 44, and 42%, respectively. In CD, small bowel localization and stricturing disease were negative prognostic factors for surgery, as was young age. Overall recurrence rate was increased by young age and current smoking. In UC, extensive colitis increased surgical risk. In UC, older age at diagnosis initially increased recurrence risk but was subsequently protective.CONCLUSIONS:This population-based IBD study showed high recurrence rates in the first year. In CD, small bowel localization, stricturing disease, and young age were predictive for disease recurrence. In UC, extensive colitis and older age at diagnosis were negative prognostic predictors.

Phenotype at diagnosis predicts recurrence rates in Crohn’s disease

Background: In Crohn’s disease (CD), studies associating phenotype at diagnosis and subsequent disease activity are important for patient counselling and health care planning. Aims: To calculate disease recurrence rates and to correlate these with phenotypic traits at diagnosis. Methods: A prospectively assembled uniformly diagnosed European population based inception cohort of CD patients was classified according to the Vienna classification for disease phenotype at diagnosis. Surgical and non-surgical recurrence rates throughout a 10 year follow up period were calculated. Multivariate analysis was performed to classify risk factors present at diagnosis for recurrent disease. Results: A total of 358 were classified for phenotype at diagnosis, of whom 262 (73.2%) had a first recurrence and 113 patients (31.6%) a first surgical recurrence during the first 10 years after diagnosis. Patients with upper gastrointestinal disease at diagnosis had an excess risk of recurrence (hazard ratio 1.54 (95% confidence interval (CI) 1.13–2.10)) whereas age ⩾40 years at diagnosis was protective (hazard ratio 0.82 (95% CI 0.70–0.97)). Colonic disease was a protective characteristic for resective surgery (hazard ratio 0.38 (95% CI 0.21–0.69)). More frequent resective surgical recurrences were reported from Copenhagen (hazard ratio 3.23 (95% CI 1.32–7.89)). Conclusions: A mild course of disease in terms of disease recurrence was observed in this European cohort. Phenotype at diagnosis had predictive value for disease recurrence with upper gastrointestinal disease being the most important positive predictor. A phenotypic North-South gradient in CD may be present, illustrated by higher surgery risks in some of the Northern European centres.

Epidemiology of inflammatory bowel disease: an update.

What have epidemiologic studies on IBD taught so far? Consistent findings are as follows: A high incidence of both CD and UC in industrialized countries and an increase in these areas of the incidence of CD during the years 1960-80 followed by a plateau phase, and a more stable pattern in UC during the same period have been found. A greater number of mild cases have probably been diagnosed recently. This also helps to explain the differences in severity and survival between community and referral centre groups. The male to female ratio is greater than 1 in UC, and this is the opposite in CD. Mortality of IBD has decreased during the past decades. As young people are especially prone to develop IBD, most of those affected will have their disease for many years. In developing IBD, genetic influences are of importance. However, epidemiologic studies strongly point to possible interactions between genetically determined features and environmental or other factors. Of these exogenic factors smoking is the most consistent, being of negative influence in CD and protective in UC. Diet and oral contraceptives may influence disease expression, and perinatal events such as viral infections may alter adult susceptibility. The question remains open whether UC and CD are one diseases entity. Similarities in the epidemiologic features of UC and CD support the idea of IBD being one disease. Other findings suggest dividing UC and CD into further subgroups: in CD it has been suggested that fibrostenotic, penetrating, and inflammatory behaviour should be considered different disease entities; in UC some groups consider ulcerative proctitis a disease entity on its own, separating it from the proximally extending colitis. In therapeutic trials this approach has proved to be of importance, and it is not inconceivable that in subgroups, with regard to aetiopathogenetic mechanisms, different factors have to be looked for.

Crohn’s disease: increased mortality 10 years after diagnosis in a Europe-wide population based cohort

Background: No previous correlation between phenotype at diagnosis of Crohn’s disease (CD) and mortality has been performed. We assessed the predictive value of phenotype at diagnosis on overall and disease related mortality in a European cohort of CD patients. Methods: Overall and disease related mortality were recorded 10 years after diagnosis in a prospectively assembled, uniformly diagnosed European population based inception cohort of 380 CD patients diagnosed between 1991 and 1993. Standardised mortality ratios (SMRs) were calculated for geographic and phenotypic subgroups at diagnosis. Results: Thirty seven deaths were observed in the entire cohort whereas 21.5 deaths were expected (SMR 1.85 (95% CI 1.30–2.55)). Mortality risk was significantly increased in both females (SMR 1.93 (95% CI 1.10–3.14)) and males (SMR 1.79 (95% CI 1.11–2.73)). Patients from northern European centres had a significant overall increased mortality risk (SMR 2.04 (95% CI 1.32–3.01)) whereas a tendency towards increased overall mortality risk was also observed in the south (SMR 1.55 (95% CI 0.80–2.70)). Mortality risk was increased in patients with colonic disease location and with inflammatory disease behaviour at diagnosis. Mortality risk was also increased in the age group above 40 years at diagnosis for both total and CD related causes. Excess mortality was mainly due to gastrointestinal causes that were related to CD. Conclusions: This European multinational population based study revealed an increased overall mortality risk in CD patients 10 years after diagnosis, and age above 40 years at diagnosis was found to be the sole factor associated with increased mortality risk.

Musculoskeletal manifestations in a population-based cohort of inflammatory bowel disease patients.

BACKGROUND Musculoskeletal disorders are the most common extra-intestinal manifestation of inflammatory bowel disease (IBD). Wide ranges of prevalence have been reported depending on the criteria used to define spondylarthropathy and on the selection of patients. We aimed to evaluate the prevalence and clinical spectrum of musculoskeletal manifestations in an inception cohort of European IBD patients. METHODS From 1 October 1991 to 30 September 1993, 202 IBD patients were diagnosed in three centres of two countries (Italy and The Netherlands) by means of a population-based inception cohort study. Of this group of patients, 160 (79%) were interviewed and examined by a rheumatologist and a gastroenterologist in the period June-September 1996. A total of 139/160 patients had an antero-posterior radiograph of the pelvis, and in 140/160 HLA-B27 was determined. RESULTS 53 (33.1%) of the 160 patients had experienced at least one musculoskeletal manifestation, 29 (18.1%) satisfied the European Spondylarthropathy Study Group (ESSG) criteria for spondylarthropathy and 5 (3.1%) satisfied the modified New York criteria for ankylosing spondylitis. However, 23 (14.4%) patients developed one or more spondylarthropathy-related manifestations without fulfilling any of the classification criteria. In patients satisfying ESSG criteria a significantly higher frequency of women (P = 0.03), of ocular and liver involvement (P = 0.01 and P = 0.03, respectively), and use of immunosuppressive drugs (P = 0.02) was observed. CONCLUSION Our study shows a high prevalence of musculoskeletal manifestations in an inception cohort of IBD patients. The clinical spectrum is broader than that defined by spondylarthropathy criteria.Background: Musculoskeletal disorders are the most common extra-intestinal manifestation of inflammatory bowel disease (IBD). Wide ranges of prevalence have been reported depending on the criteria used to define spondylarthropathy and on the selection of patients. We aimed to evaluate the prevalence and clinical spectrum of musculoskeletal manifestations in an inception cohort of European IBD patients. Methods: From 1 October 1991 to 30 September 1993, 202 IBD patients were diagnosed in three centres of two countries (Italy and The Netherlands) by means of a population-based inception cohort study. Of this group of patients, 160 (79%) were interviewed and examined by a rheumatologist and a gastroenterologist in the period June-September 1996. A total of 139/160 patients had an anteroposterior radiograph of the pelvis, and in 140/160 HLA-B27 was determined. Results: 53 (33.1%) of the 160 patients had experienced at least one musculoskeletal manifestation, 29 (18.1%) satisfied the European Spondylarthropathy Study Group (ESSG) criteria for spondylarthropathy and 5 (3.1%) satisfied the modified New York criteria for ankylosing spondylitis. However, 23 (14.4%) patients developed one or more spondylarthropathy-related manifestations without fulfilling any of the classification criteria. In patients satisfying ESSG criteria a significantly higher frequency of women ( P = 0.03), of ocular and liver involvement ( P = 0.01 and P = 0.03, respectively), and use of immunosuppressive drugs ( P = 0.02) was observed. Conclusion: Our study shows a high prevalence of musculoskeletal manifestations in an inception cohort of IBD patients. The clinical spectrum is broader than that defined by spondylarthropathy criteria.

Fatigue and health-related quality of life in inflammatory bowel disease: results from a population-based study in the Netherlands: the IBD-South Limburg cohort.

Background: The importance of fatigue in chronic disease has been increasingly recognized; however, little is known about fatigue in inflammatory bowel disease (IBD). The aim of the present study was to investigate the prevalence and severity of fatigue and the impact on health‐related quality of life (HRQoL) in patients included in a population‐based IBD cohort in the Netherlands. Methods: IBD patients, diagnosed between January 1st, 1991, and January 1st, 2003, were followed up for a median of 7.1 years. They completed a questionnaire, which included a disease activity score, the Multidimensional Fatigue Inventory (MFI‐20), the Inflammatory Bowel Disease Questionnaire (IBDQ), and the Short Form health survey (SF‐36). Hemoglobin levels were recorded. Results: Data were available in 304 Crohns disease (CD), 368 ulcerative colitis (UC), and 35 indeterminate colitis (IC) patients. During quiescent disease, the prevalence of fatigue was nearly 40%. MFI‐20 and HRQoL scores were significantly worse in IBD patients having active disease. In a multivariate analysis, disease activity was positively related with the level of fatigue in both CD and UC. In UC, anemia influenced the general fatigue score independently of disease activity. Disease activity as well as fatigue were independently associated with an impaired IBDQ. Conclusions: In IBD, even in remission, fatigue is an important feature. Both in CD and in UC, fatigue determined HRQoL independently of disease activity or anemia. This implies that in IBD patients physicians need to be aware of fatigue in order to better understand its impact and to improve the HRQoL. (Inflamm Bowel Dis 2010)

The impact of inflammatory bowel disease on labor force participation: Results of a population sampled case-control study

IntroductionInflammatory bowel diseases are chronic conditions that might cause a severe impact on social life. The aim of the study was to assess employment, chronic work disability, and sick leave in patients with inflammatory bowel disease. MethodsA postal questionnaire was sent to 984 patients with inflammatory bowel disease and 1504 controls. Age- and gender-adjusted employment and chronic work disability ratios and rates were calculated using indirect standardization. In subjects in paid employment, proportions of those having an episode of sick leave and lost workdays were analyzed. Logistic regression was used to assess the contribution of age, gender, education, and course of disease. ResultsThe results of 680 (69%) patients and 715 (48%) controls could be analyzed. For the entire group of patients, employment was 6.5% lower, compared with controls (95% CI: 4.0–9.0). Chronic work disability was 17.1% higher than expected (95% CI: 15.1–19.1). In those in paid employment, 62% of patients compared with 53% of controls had experienced one or more episodes of sick leave during the past year (p = 0.002). This resulted in 19.2 versus 11.8 days of sick leave per subject per year for patients and controls respectively (p = 0.002). Relative to controls, the risk of chronic work disability was more increased in younger (p = 0.02) and higher educated (p = 0.02) patients. Course of disease contributed to chronic work disability and sick leave. ConclusionIBD has a significant impact on labor force participation that is higher in CD compared with UC and highest in younger and more highly educated patients.

Systematic review: has disease outcome in Crohn's disease changed during the last four decades?

Background : Disease outcome in Crohns disease might have changed during the last four decades. Disease outcome measurement in Crohns disease has methodological difficulties because of patient selection and lack of proper definition of diagnostic and outcome measurement criteria.

Validation of the Dutch Translation of the Inflammatory Bowel Disease Questionnaire (IBDQ): A Health-Related Quality of Life Questionnaire in Inflammatory Bowel Disease

Health-related quality of life assessment can benefit several groups involved with health care. The aim of our study was to assess construct validity, reliability, discriminant ability and sensitivity to change of the Dutch translation of the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific quality-of-life questionnaire. A group of 120 IBD patients completed the IBDQ and two Visual Analogue Scales concerning general well-being and bowel function twice. Fifty-two patients also completed the Short-Form 36 twice. Disease activity was assessed once. Correlations between the IBDQ scores and the global assessments were reasonably high and the IBDQ was shown to be discriminative. High intraclass correlation coefficients between both measurements of the IBDQ were observed in patients who reported no change in bowel complaints. In contrast, significant differences were found between both moments in patients who reported change. The Dutch IBDQ proved to be valid, discriminative and reliable.

Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: a randomised, double-blind, placebo controlled trial (ADAFI)

Objective To assess whether a combination of adalimumab and ciprofloxacin is superior to adalimumab alone in the treatment of perianal fistulising Crohns disease (CD). Design Randomised, double-blind, placebo controlled trial in eight Dutch hospitals. In total, 76 CD patients with active perianal fistulising disease were enrolled. After adalimumab induction therapy (160/80 mg week 0, 2), patients received 40 mg every other week together with ciprofloxacin 500 mg or placebo twice daily for 12 weeks. After 12 weeks, adalimumab was continued. Follow-up was 24 weeks. Primary endpoint (clinical response) was defined as 50% reduction of fistulas from baseline to week 12. Secondary endpoints included remission (closure of all fistulas), Perianal Crohns Disease Activity Index, Crohns Disease Activity Index (CDAI) and Inflammatory Bowel Disease Questionnaire (IBDQ). Results Clinical response was observed in 71% of patients treated with adalimumab plus ciprofloxacin and in 47% treated with adalimumab plus placebo (p=0.047). Likewise, remission rate at week 12 was significantly higher (p=0.009) in the combination group (65%) compared with adalimumab plus placebo (33%). Combination treatment was associated with a higher mean CDAI change and mean IBDQ change at week 12 (p=0.005 and p=0.009, respectively). At week 24, no difference in clinical response between the two treatment groups was observed (p=0.22). No difference in safety issues was observed. Conclusions Combination therapy of adalimumab and ciprofloxacin is more effective than adalimumab monotherapy to achieve fistula closure in CD. However, after discontinuation of antibiotic therapy, the beneficial effect of initial coadministration is not maintained. Trial registration ClinicalTrials.gov Identifier: NCT00736983.