Bjørn Moum

Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study)

Objective. Cohort studies of unselected and newly diagnosed patients are essential for a better understanding of the prognosis in ulcerative colitis (UC). The aim of this study was to evaluate the course of UC in a population-based inception cohort during the first 10 years, and to identify prognostic risk factors based on information gathered at diagnosis. Material and methods. From 1990 to 1994, a population-based cohort of 843 patients with inflammatory bowel disease was enrolled in South-Eastern Norway. The cohort was systematically followed-up at 1, 5 and 10 years after diagnosis. Results. Of 519 patients with UC, 423 completed the 10-year follow-up, 53 died and 43 were lost to follow-up. The mortality risk was not increased compared with that in the general population. The cumulative colectomy rate after 10 years was 9.8% (95% CI: 7.4–12.4%). Initial presentation with extensive colitis and erythrocyte sedimentation rate (ESR) ≥30 mm/h was associated with an increased hazard ratio (HR) (3.57, 95% CI: 1.60–7.96) and age ≥50 years at diagnosis, with reduced HR (0.28, 95% CI: 0.12–0.65) for subsequent colectomy. Relapsing disease was noted in 83%, but half (48%) of the patients were relapse free during the last 5 years. One-fifth (69/288) of patients with proctitis or left-sided colitis had progressed to extensive colitis. Conclusions. The prognosis for UC during the first 10 years was generally good. The colectomy rate was low, and a large proportion of patients were in remission as time progressed. Patients with initially extensive colitis and elevated ESR could benefit from an early potent medical treatment strategy.

Association of NOD2 (CARD 15) genotype with clinical course of Crohn's disease: a cohort study

BACKGROUND Crohns disease is a heterogeneous disorder for which NOD2 (CARD 15) has been identified as a susceptibility gene. We investigate the relation between NOD2 genotype and phenotypic characteristics of patients with Crohns disease. METHODS Hypotheses about the relation between NOD2 genotype and Crohns disease phenotype were generated retrospectively from a group of 446 German patients with this disorder. Positive findings (p<0.10) were verified in prospectively established cohorts of 106 German and 55 Norwegian patients with Crohns disease. All patients were genotyped for the main coding mutations in NOD2, denoted SNP8, SNP12, and SNP13, with Taqman technology. FINDINGS In the retrospective cohort, six clinical characteristics showed noteworthy haplotype association: fistulising, ileal, left colonic and right colonic disease, stenosis, and resection. In the German prospective cohort, these haplotype associations could be replicated for ileal (p=0.006) and right colonic disease (p < or =0.001). A similar trend was noted in the Norwegian patients. INTERPRETATION We recorded a distinct relation between NOD2 genotype and phenotype of Crohns disease. Test strategies with NOD2 variations to predict the clinical course of Crohns disease could lead to the development of new therapeutic paradigms.

Geographical variability and environmental risk factors in inflammatory bowel disease

The changing epidemiology of inflammatory bowel disease (IBD) across time and geography suggests that environmental factors play a major role in modifying disease expression. Disease emergence in developing nations suggests that epidemiological evolution is related to westernisation of lifestyle and industrialisation. The strongest environmental associations identified are cigarette smoking and appendectomy, although neither alone explains the variation in incidence of IBD worldwide. Urbanisation of societies, associated with changes in diet, antibiotic use, hygiene status, microbial exposures and pollution have been implicated as potential environmental risk factors for IBD. Changes in socioeconomic status might occur differently in different geographical areas and populations and, consequently, it is important to consider the heterogeneity of risk factors applicable to the individual patient. Environmental risk factors of individual, familial, community-based, country-based and regionally based origin may all contribute to the pathogenesis of IBD. The geographical variation of IBD provides clues for researchers to investigate possible environmental aetiological factors. The present review aims to provide an update of the literature exploring geographical variability in IBD and to explore the environmental risk factors that may account for this variability.

C -Reactive Protein: A Predictive Factor And Marker Of Inflammation In Inflammatory Bowel Disease Results From A Prospective Population-Based Study

Background and aims: C-reactive protein (CRP) levels are often used in the follow-up of patients with inflammatory bowel disease (IBD). The aims of this study were to establish the relationship of CRP levels to disease extent in patients with ulcerative colitis and to phenotype in patients with Crohn’s disease, and to investigate the predictive value of CRP levels for disease outcome. Methods: CRP was measured at diagnosis and after 1 and 5 years in patients diagnosed with IBD in south-eastern Norway. After 5 years, 454 patients with ulcerative colitis and 200 with Crohn’s disease were alive and provided sufficient data for analysis. Results: Patients with Crohn’s disease had a stronger CRP response than did those with ulcerative colitis. In patients with ulcerative colitis, CRP levels at diagnosis increased with increasing extent of disease. No differences in CRP levels at diagnosis were found between subgroups of patients with Crohn’s disease as defined according to the Vienna classification. In patients with ulcerative colitis with extensive colitis, CRP levels above 23 mg/l at diagnosis predicted an increased risk of surgery (odds ratio (OR) 4.8, 95% confidence interval (CI) 1.5 to 15.1, p = 0.02). In patients with ulcerative colitis, CRP levels above 10 mg/l after 1 year predicted an increased risk of surgery during the subsequent 4 years (OR 3.0, 95% CI 1.1 to 7.8, p = 0.02). A significant association between CRP levels at diagnosis and risk of surgery was found in patients with Crohn’s disease and terminal ileitis (L1), and the risk increased when CRP levels were above 53 mg/l in this subgroup (OR 6.0, 95% CI 1.1 to 31.9, p = 0.03). Conclusions: CRP levels at diagnosis were related to the extent of disease in patients with ulcerative colitis. Phenotype had no influence on CRP levels in patients with Crohn’s disease. CRP is a predictor of surgery in subgroups of patients with either ulcerative colitis or Crohn’s disease.

Esomeprazole 20 mg maintains symptom control in endoscopy‐negative gastro‐oesophageal reflux disease: a controlled trial of ‘on‐demand’ therapy for 6 months

Most patients with gastro‐oesophageal reflux disease (GERD), regardless of endoscopic status, suffer symptomatic relapse within 6 months of stopping acid suppressant therapy.

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.

Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial

BACKGROUND TNF inhibitors have improved treatment of Crohns disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis, but are expensive therapies. The aim of NOR-SWITCH was to examine switching from originator infliximab to the less expensive biosimilar CT-P13 regarding efficacy, safety, and immunogenicity. METHODS The study is a randomised, non-inferiority, double-blind, phase 4 trial with 52 weeks of follow-up. Adult patients on stable treatment with infliximab originator treated in a hospital setting for at least 6 months were eligible for participation. Patients with informed consent were randomised in a 1:1 ratio to either continued infliximab originator or to switch to CT-P13 treatment, with unchanged dosing regimen. Data were collected at infusion visits in 40 Norwegian study centres. Patients, assessors, and patient care providers were masked to treatment allocation. The primary endpoint was disease worsening during 52-week follow-up. 394 patients in the primary per-protocol set were needed to show a non-inferiority margin of 15%, assuming 30% disease worsening in each group. This trial is registered with ClinicalTrials.gov, number NCT02148640. FINDINGS Between Oct 24, 2014, and July 8, 2015, 482 patients were enrolled and randomised (241 to infliximab originator, 241 to CT-P13 group; one patient was excluded from the full analysis and safety set for CT-P13) and 408 were included in the per-protocol set (202 in the infliximab originator group and 206 in the CT-P13 group). 155 (32%) patients in the full analysis set had Crohns disease, 93 (19%) had ulcerative colitis, 91 (19%) had spondyloarthritis, 77 (16%) had rheumatoid arthritis, 30 (6%) had psoriatic arthritis, and 35 (7%) had chronic plaque psoriasis. Disease worsening occurred in 53 (26%) patients in the infliximab originator group and 61 (30%) patients in the CT-P13 group (per-protocol set; adjusted treatment difference -4·4%, 95% CI -12·7 to 3·9). The frequency of adverse events was similar between groups (for serious adverse events, 24 [10%] for infliximab originator vs 21 [9%] for CT-P13; for overall adverse events, 168 [70%] vs 164 [68%]; and for adverse events leading to discontinuation, nine [4%] vs eight [3%], respectively). INTERPRETATION The NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 was not inferior to continued treatment with infliximab originator according to a prespecified non-inferiority margin of 15%. The study was not powered to show non-inferiority in individual diseases. FUNDING Norwegian Ministry of Health and Care Services.

Health-related quality of life in patients with inflammatory bowel disease measured with the short form-36: Psychometric assessments and a comparison with general population norms

Background: We compared health‐related quality of life (HRQOL) in a population‐based cohort of Norwegian patients with inflammatory bowel disease (IBD) with a normal reference population by means of the short form‐36 (SF‐36) questionnaire, including the effect of age, sex, educational status, and symptom severity and the psychometric properties of the questionnaire. Methods: The SF‐36 was self‐administered and was answered by the patients at the hospital at 2 occasions that were 6 months apart. Results: Five hundred fourteen patients with IBD were eligible for analysis: 348 with ulcerative colitis (UC) and 166 with Crohns disease (CD). The comparison group consisted of 2323 Norwegian people. The dimension scores for SF‐36 were significantly lower in 6 of 8 dimensions for patients with UC and in 7 of 8 dimensions for patients with CD than for the reference population. In both patients with UC and patients with CD, we found lower scores in elderly patients, which also was found in the background population. Women scored lower than men in all dimension scores. In both patients with UC and patients with CD, there was a statistically significant reduction in HRQOL score with increasing symptoms. The SF‐36 has satisfactory reliability and discriminant ability for scores for all dimensions in both patients with UC and patients with CD. However, when measuring responsiveness, the figures were generally low. This finding, together with the high ceiling effects, may indicate that the SF‐36 has limitations regarding detecting deterioration or improvement over time. Conclusion: We have shown that HRQOL in a Norwegian population‐based cohort of patients with IBD, measured with the SF‐36, is lower than that of a Norwegian reference population. In general, the SF‐36 was found to have satisfactory psychometric properties in this IBD population.

Hospitalisations and surgery in Crohn's disease

Hospitalisation and surgery are considered to be markers of more severe disease in Crohns disease. These are costly events and limiting these costs has emerged as one rationale for the cost of expensive biologic therapies. The authors sought to review the most recent international literature to estimate current hospitalisation and surgery rates for Crohns disease and place them in the historical context of where they have been, whether they have changed over time, and to compare these rates across different jurisdictions. It is in this context that the authors could set the stage for interpreting some of the early data and studies that will be forthcoming on rates of hospitalisation and surgery in an era of more aggressive biologic therapy. The most recent data from Canada, the United Kingdom and Hungary all suggest that surgical rates were falling prior to the advent of biologic therapy, and continue to fall during this treatment era. The impact of biologic therapy on surgical rates will have to be analysed in the context of evolving reductions in developed regions before biologic therapy was even introduced. Whether more aggressive medical therapy will decrease the requirement for surgery over long periods of time remains to be proven.

Incidence of Crohn's Disease in Four Counties in Southeastern Norway, 1990–93 A Prospective Population-Based Study

BACKGROUND Standardized criteria for Crohns disease (CD) have only recently been developed, and prospective community-based incidence studies have been performed only during the past 3 decades. Geographic variations in incidence may therefore be due to differences in study design. METHODS From 1 January 1990 to 31 December 1993 all new cases of CD in four counties in southeastern Norway were prospectively registered. RESULTS A total of 225 new cases yielded an annual incidence of 5.8/10(5), with the highest incidence in mixed rural-urban areas. A peak of 11.2/10(5) in the annual incidence was found for the age group 15 to 24 years, with no significant differences in the overall annual incidence by gender. An average duration of 6 months of disease before diagnosis was unchanged during the 4 years. About half of the patients had isolated colonic disease, and one-quarter had isolated small-bowel disease. CONCLUSIONS This study confirms the high incidence figures for Scandinavia, with a particularly high incidence in mixed rural-urban areas. Ileocolonoscopy improves the accuracy of the diagnosis and of the determination of disease extent, which may have therapeutic implications for the treatment and follow-up of patients.