Idar Lygren

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.

Ulcerative colitis and clinical course: Results of a 5‐year population‐based follow‐up study (the IBSEN study)

Background: The majority of studies concerning the clinical course and prognosis in ulcerative colitis (UC) are old, retrospective in design, or hospital based. We aimed to identify clinical course and prognosis in a prospective, population‐based follow‐up study Materials and Methods: Patients diagnosed with inflammatory bowel disease (IBD) or possible IBD in southeastern Norway during the period 1990–1994 were followed prospectively for 5 years. The evaluation at 5 years included an interview, clinical examination, laboratory tests, and colonoscopy. Results: Of 843 patients diagnosed with IBD, 454 patients who had definite UC and for whom there were sufficient data for analysis were alive 5 years after inclusion in the study. The frequency of colectomy in this population was 7.5%. Forty‐one percent of the patients were not taking any kind of medication for IBD at 5 years. Of the patients initially diagnosed with proctitis, 28% had progressed during the observation period, 10% to extensive colitis. The majority of the patients (57%) had no intestinal symptoms at 5 years, and only a minority (7%) had symptoms that interfered with everyday activities. Among the patients who underwent colonoscopy at the 5‐year visit, symptoms were frequently reported in patients without macroscopic inflammation (44%). A relapse‐free course was observed in 22% of the patients. A decrease in symptoms during the follow‐up period was the most frequent course taken by the disease and was observed in 59% of the cases. The extent of disease was unrelated to symptoms at 5 years and also to relapse rate and course of disease during the 5‐year period. Conclusions: The disease course and prognosis of UC appears better than previously described in the literature. The frequency of surgery was low, and only a minority of the patients had symptoms that interfered with their everyday activities 5 years after diagnosis.

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.

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.

Clinical course in Crohn's disease: Results of a five-year population-based follow-up study (the IBSEN study)

Background. There are few population-based, prospective studies on the clinical course in patients with Crohns disease (CD). Aim. To extend the observation period in a population-based prospective study (the IBSEN study) to find out more about the initial 5-year clinical course in CD patients and to relate the findings to the Vienna classification. Methods. All patients diagnosed with inflammatory bowel disease (IBD) in southeastern Norway in the 4 years 1990–1993 were followed prospectively. The patients were invited to a systematic follow-up visit at their local hospital 1 and 5 years after inclusion in the study. The visits included a structured interview, a clinical examination and colonoscopy. Results. Out of 843 patients initially diagnosed with IBD, 200 patients with definite CD were alive and had sufficient data for analysis 5 years after diagnosis. Changes in disease localization and behaviour in relation to the Vienna classification were observed in 27 (13.5%) and 35 patients (17.5%), respectively. During the observation period, 56 patients (28%) underwent surgery with intestinal resection, and half of these had disease localized in the terminal ileum. At the time of the 5-year visit, oral sulfasalazin and 5-aminosalicylic acid (5-ASA) were the most frequently used medications (by 54% of the patients), while oral glucocorticosteroids and azathioprine were being used by 25% and 13%, respectively. Seventy-two percent of the patients had taken oral glucocorticosteroids at some time in the course of the 5-year period. The majority of the patients had intestinal symptoms at 5 years, but only 16% had symptoms that interfered with everyday activities. Fourteen percent of the patients had had a relapse-free 5-year course; however, relapse was not related to the initial Vienna classification. When the patients described the clinical course, 44% reported an improvement in symptoms during the follow-up period. Conclusions: The 5-year clinical course in an unselected cohort of CD patients was mostly mild. The frequency of surgery was lower than that observed in other studies and only a minority of the patients had symptoms that interfered with everyday activities 5 years after the initial diagnosis. The Vienna classification predicted the risk of surgery, but did not predict symptoms at 5 years, relapses during the observation period or the course of disease as described by the patients.

Clinical Course during the 1st Year after Diagnosis in Ulcerative Colitis and Crohn's Disease: Results of a Large, Prospective Population-based Study in Southeastern Norway, 1990-93

BACKGROUND The clinical course and prognosis in ulcerative colitis (UC) and Crohns disease (CD) have been described in many studies, mostly retrospective. Such studies are hampered by problems such as inclusion over a long time period, proper definitions, incomplete case records, and outdated methods of diagnosis. In a prospective study we identified 846 patients with inflammatory bowel disease (IBD) over a 4-year period from 1990 to 1993. Uniform diagnostic and therapeutic strategies were used as a basis for later assessment of the short-term clinical course in different subgroups of UC and CD and analysis of potential risk factors for relapse or surgery. METHODS At the time of follow-up, a mean of 16.2 months after diagnosis, 496 UC patients and 232 CD patients, altogether 98%, were available for evaluation. A colonoscopy was performed in 88% (410 of 465) of the UC patients attending a clinical examination and in 76% (164 of 216) of the CD patients. RESULTS Eleven patients with UC and five patients with CD died during follow-up, four of complications related to IBD. The cumulative 1-year relapse rate in the remaining patients was 50% for UC and 47% for CD. Of the patients with relapses 11 % of the UC patients and 10% of the CD patients had a chronic relapsing course without any difference with regard to the various disease categories in UC or CD. An increased risk of relapse was found in patients less than 50 years old only in UC. In UC a higher risk for surgery was found in patients with extensive colitis compared with left-sided colitis (P = 0.011), and CD patients with small-bowel involvement had a higher risk of surgery than patients with disease confined to the colon (P = 0.021). There was no excess risk of relapse or surgery in smokers as compared with non-smokers or former smokers, nor did the risk of relapse vary with the level of cigarette consumption in either UC or CD patients. CONCLUSION The high relapse rate of around 50% for both UC and CD calls for a review of the existing treatment. Further follow-up will be necessary to improve our ability to make clinical decisions relating to medical and surgical treatment options.

Relationship between sick leave, unemployment, disability, and health‐related quality of life in patients with inflammatory bowel disease

Background The goal of this study was to determine the rate of work disability, unemployment, and sick leave in an unselected inflammatory bowel disease (IBD) cohort and to measure the effect of working status and disability on the patients health‐related quality of life (HRQOL). Materials and Methods All eligible patients were clinically examined and interviewed at the 5‐year follow‐up visit. In addition, they completed the 2 HRQOL questionnaires, the Short Form‐36 Health Survey (SF‐36) and the Inflammatory Bowel Disease Questionnaire validated for use in Norway (N‐IBDQ). Data regarding sick leave, unemployment, and disability pension (DP) also were collected. Results All together, 495 patients were or had been in the workforce during the 5‐year follow‐up period since diagnosis. Forty‐two patients (8.5%) were on DP compared with 8.8% in the background population. Women with Crohns disease (CD) had the highest probability of receiving DP (24.6%). A total of 58 patients (11.7%) reported they were unemployed at 5 years. This was equally distributed between men and women but was more frequent in patients with ulcerative colitis. Sick leave for all causes was reported in 47% with ulcerative colitis and 53% with CD, whereas IBD‐related sick leave was reported in 18% and 23%, respectively. A majority (75%) had been sick <4 weeks, and a relatively small number of patients (25%) contributed to a large number of the total sick leave days. Both unemployment and DP reduced HRQOL scores, but the most pronounced effect on HRQOL was found in patients reporting IBD‐related sick leave, measured with SF‐36 and N‐IBDQ. The observed differences also were highly clinically significant. Multiple regression analysis confirmed that IBD‐related sick leave was the independent variable with the strongest association to the observed reduction in HRQOL scores. Conclusions Unemployment or sick leave is more common in IBD patients than in the Norwegian background population. The number of patients receiving DP is significantly increased in women with CD but not in the other patient groups. Unemployment, sick leave, and DP are related to the patients HRQOL in a negative way, but this effect is most pronounced in patients reporting IBD‐related sick leave.

Consecutive fecal calprotectin measurements to predict relapse in patients with ulcerative colitis receiving infliximab maintenance therapy

Background: This study examined whether fecal calprotectin can be used in daily practice as a marker to monitor patients with ulcerative colitis (UC) receiving infliximab maintenance therapy. Methods: This prospective multicenter study enrolled adult patients with UC in clinical remission under infliximab maintenance therapy. Fecal calprotectin levels were measured every 4 weeks. Sigmoidoscopies were performed at inclusion and at study end. Relapse was defined as a clinical need for change in treatment or an endoscopic Mayo subscore of ≥2 at week 52. Sustained deep remission was defined as a partial Mayo score <3 at all points and an endoscopic Mayo score 0 at week 52. Results: Full analysis was possible for 87 of 113 included patients with UC (77%). Of these patients, 30 (34.4%) were considered to be in sustained deep remission and 13 (14.9%) to have relapsed. Calprotectin levels in patients with sustained deep remission remained very low (median < 40 mg/kg at all time points). Patients who flared had significantly higher calprotectin levels (median > 300 mg/kg) already 3 months before the flare. Further receiver operator curve analysis suggested that a calprotectin level >300 mg/kg had a reasonable sensitivity (58.3%) and specificity (93.3%) to model flare. Two consecutive calprotectin measurements of >300 mg/kg with 1-month interval were identified as the best predictor of flare (61.5% sensitivity and 100% specificity). Conclusions: Fecal calprotectin can be used in daily practice to monitor patients with UC receiving infliximab maintenance therapy. Two consecutive measurements >300 mg/kg is more specific than a single measurement for predicting relapse.

Change of diagnosis during the first five years after onset of inflammatory bowel disease: results of a prospective follow-up study (the IBSEN Study).

Objective. An exact diagnosis of inflammatory bowel disease (IBD) and further subclassification may be difficult even after clinical, radiological and histological examinations. A correct subclassification is important for the success of both medical and surgical therapeutic strategies, but there is a dearth of information available on the frequency of changes in diagnosis in population-based studies. The objective of this work was prospectively to re-evaluate the diagnosis in an unselected cohort of IBD patients during the first five years after the initial diagnosis. Material and methods. Patients classified as IBD or possible IBD in the period 1990–94 (the IBSEN cohort) had their diagnosis re-evaluated after 1 and 5 years. Initially, the patients were classified as ulcerative colitis (UC), Crohns disease (CD), indeterminate colitis (IC) or possible IBD. At the 5-year visit, patients were classified as UC, CD or non-IBD. Results. A total of 843 patients (518 UC, 221 CD, 40 IC and 64 possible IBD) were identified. Clinical information was available for 94% of the patients who survived after 5 years. A change in diagnosis was found in 9% of the patients initially classified as UC or CD. A change to non-IBD was more frequent than a change between UC and CD. A large proportion of patients initially classified as IC or possible IBD were diagnosed as non-IBD after 5 years (22.5% versus 50%). When IBD was confirmed in these groups, UC was more frequent than CD. Two changes in diagnosis during follow-up were observed in 2.8% of the patients; this was more frequent in patients initially classified as IC or possible IBD. Conclusions. There are obvious diagnostic problems in a minority of patients with IBD; a systematic follow-up is therefore important in these patients.

MRI of the small bowel with oral contrast or nasojejunal intubation in Crohn's disease: randomized comparison of patient acceptance.

Objective. Magnetic resonance imaging of the small bowel with an oral contrast (MRI per os) is believed to generate fewer adverse symptoms compared with installation of the contrast in a nasojejunal catheter (MRE). However, there is very little evidence to support this assumption. The aim of this study was to evaluate the compliance of patients examined with both of these MRI methods. Material and methods. Patients with suspected or known Crohns disease referred for MRI of the small bowel underwent both MRI per os and MRE within 7 days. A questionnaire was answered immediately and 24 h after the procedure. Adverse symptoms were graded on a visual analogue scale (VAS). Responses were compared with paired and independent sample t-tests and signed-rank tests. Correlation of each symptom to the overall discomfort was evaluated with Spearmans correlation coefficient. Results. Thirty-eight patients (18 F, 20 M) were included in the analysis. Abdominal pain and discomfort were lower with MRI per os than with MRE (mean VAS pain score immediately after: 10 mm and 33 mm, respectively, p<0.001; mean VAS discomfort score 24 h after: 18 mm and 62 mm, respectively, p<0.001). Nausea and abdominal pain were correlated with overall discomfort after MRI per os (r=0.56 for both, p<0.001). No symptoms were significantly correlated with discomfort experienced with MRE. More patients accepted repeat MRI per os examination (n=36) than MRE (n=22, p=0.001). Conclusion. Patients preferred and experienced less abdominal pain and discomfort with MRI per os than with MRE.