Crohn Disease: Oldenburg B

Hommes DW, Oldenburg B, van Bodegraven AA, van Hogezand RA, de Jong DJ, Romberg-Camps MJ, van der Woude J, Dijkstra G, Anonymous00077. · Academic Medical Centre, Amsterdam, the Netherlands. · Neth J Med. · Pubmed #16929083 links to  free full text

Abstract: Infliximab is an accepted induction and maintenance treatment for patients with Crohn's disease. The effectiveness of infliximab has been demonstrated for both active luminal disease and for enterocutaneous fistulisation. In addition, infliximab can be administered for extraintestinal symptoms of Crohn's disease, such as pyoderma gangrenosum, uveitis and arthropathy. Maintenance treatment with infliximab is effective and is regarded as safe as long as the necessary safety measures are heeded. Infusion reactions occur in 3 to 17% of the patients and are associated with the formation of antibodies to infliximab. A reduction in infusion reactions is possible by the concurrent administration of steroids and the use of immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate). Furthermore, immunosuppressants increase the duration of the response to infliximab. For these reasons, the concomitant use of immunosuppressants with infliximab is recommended. Infections and most specifically tuberculosis need to be ruled out before infliximab is administered. Up to now, there are no indications for a connection between an increased risk for malignancies and treatment with infliximab.

Minderhoud IM, Samsom M, Oldenburg B. · Department of Gastroenterology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands. · Inflamm Bowel Dis. · Pubmed #17663422 links to  free full text

Abstract: A number of disease-specific instruments have been created over the last 30 years to assess disease activity in Crohn's disease (CD). These disease activity indices are constituted of clinical and laboratory parameters and their role in predicting disease activity and the course of disease has been reviewed various times. Currently, the severity of mucosal inflammation, assessed by endoscopy, is considered the gold standard for disease activity in CD. In the present review the most frequently used endoscopic disease activity indices and the correlation between mucosal inflammation and clinical disease activity indices, quality of life questionnaires, and biochemical markers is critically appraised. We conclude that no clinical disease activity index or single laboratory parameter of inflammation reliably predicts the mucosal inflammatory disease activity. A new, easy-to-use and robust activity index predicting mucosal inflammation is highly needed to assess the response to investigational drugs in trials and the effect of therapeutical interventions in clinical practice.

Koelewijn C, Schrijvers A, Oldenburg B. · Department of Gastroenterology, University Medical Centre Utrecht, Utrecht, the Netherlands. · Neth J Med. · Pubmed #16929082 links to  free full text

This publication has no abstract.

van Balkom BP, Schoon EJ, Stockbrügger RW, Wolters FL, van Hogezand RA, van Deventer SJ, Oldenburg B, van Dullemen HM, Russel MG. · Department of Gastroenterology, University Hospital Maastricht, NL-6202 AZ Maastricht, The Netherlands. · Aliment Pharmacol Ther. · Pubmed #12030951 links to  free full text

Abstract: BACKGROUND: Infusion of anti-tumour necrosis factor-alpha appears to be highly effective in patients with Crohn's disease. AIM: To assess the effect of infliximab on the quality of life in patients with active or fistulizing disease, as measured by the inflammatory bowel disease questionnaire, and to examine the impact on its four dimensions. METHODS: An observational study was conducted in 65 patients. An infusion of 5 mg/kg infliximab was given at week 0 in patients with active disease and at week 0, 2 and 6 in fistulizing disease. Changes from baseline in the total and dimensional inflammatory bowel disease questionnaire scores were calculated and compared between the patient groups. Potential predictors of change in the quality of life were identified. RESULTS: In the active disease group, at week 4, the mean total and dimensional inflammatory bowel disease questionnaire scores improved compared to baseline (P < 0.001). In the fistulizing group, at week 6, all scores changed from baseline (P < 0.05). Improvement in the total inflammatory bowel disease questionnaire score correlated well with the improvement of the Crohn's disease activity index. Systemic and social scores improved more than bowel and emotional scores. Inflammatory Crohn's disease and a young age at diagnosis were predictors for a better response to infliximab therapy. CONCLUSIONS: Infliximab therapy improves all dimensions of the quality of life in patients with Crohn's disease.

van Rijn AF, Fockens P, Siersema PD, Oldenburg B. · Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam 1105AZ, The Netherlands. · World J Gastroenterol. · Pubmed #19132774 links to  free full text

Abstract: AIM: To study adherence to the widely accepted surveillance guidelines for patients with long-standing colitis in The Netherlands. METHODS: A questionnaire was sent to all 244 gastroenterologists in The Netherlands. RESULTS: The response rate was 63%. Of all gastroenterologists, 95% performed endoscopic surveillance in ulcerative colitis (UC) patients and 65% in patients with Crohn's colitis. The American Gastroenterological Association (AGA) guidelines were followed by 27%, while 27% and 46% followed their local hospital protocol or no specific protocol, respectively. The surveillance was correctly initiated in cases of pancolitis by 53%, and in cases of left-sided colitis by 44% of the gastroenterologists. Although guidelines recommend 4 biopsies every 10 cm, less than 30 biopsies per colonoscopy were taken by 73% of the responders. Only 31%, 68% and 58% of the gastroenterologists referred patients for colectomy when low-grade dysplasia, high-grade dysplasia (HGD) or Dysplasia Associated Lesion or Mass (DALM) was present, respectively. CONCLUSION: Most Dutch gastroenterologists perform endoscopic surveillance without following international recommended guidelines. This practice potentially leads to a decreased sensitivity for dysplasia, rendering screening for colorectal cancer in this population highly ineffective.

Weersma RK, Stokkers PC, van Bodegraven AA, van Hogezand RA, Verspaget HW, de Jong DJ, van der Woude CJ, Oldenburg B, Linskens RK, Festen EA, van der Steege G, Hommes DW, Crusius JB, Wijmenga C, Nolte IM, Dijkstra G, Anonymous00042. · Department of Gastroenterology and Hepatology, University Medical Center Groningen and University of Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands. · Gut. · Pubmed #18824555 No free full text.

Abstract: BACKGROUND: Crohn's disease and ulcerative colitis have a complex genetic background. We assessed the risk for both the development and severity of the disease by combining information from genetic variants associated with inflammatory bowel disease (IBD). METHODS: We studied 2804 patients (1684 with Crohn's disease and 1120 with ulcerative colitis) and 1350 controls from seven university hospitals. Details of the phenotype were available for 1600 patients with Crohn's disease and for 800 with ulcerative colitis. Genetic association for disease susceptibility was tested for the nucleotide-binding and oligomerisation domain 2 gene (NOD2), the IBD5 locus, the Drosophila discs large homologue 5 and autophagy-related 16-like 1 genes (DLG5 and ATG16L1) and the interleukin 23 receptor gene (IL23R). Interaction analysis was performed for Crohn's disease using the most associated single nucleotide polymorphism (SNP) for each locus. Odds ratios were calculated in an ordinal regression analysis with the number of risk alleles as an independent variable to analyse disease development and severity. RESULTS: Association with Crohn's disease was confirmed for NOD2, IBD5, DLG5, ATG16L1 and IL23R. Patients with Crohn's disease carry more risk alleles than controls (p = 3.85 x 10(-22)). Individuals carrying an increasing number of risk alleles have an increasing risk for Crohn's disease, consistent with an independent effects multiplicative model (trend analysis p = 4.25 x 10(-23)). Patients with Crohn's disease with a more severe disease course, operations or an age of onset below 40 years have more risk alleles compared to non-stricturing, non-penetrating behaviour (p = 0.0008), no operations (p = 0.02) or age of onset above 40 years (p = 0.028). CONCLUSION: Crohn's disease is a multigenic disorder. An increase in the number of risk alleles is associated with an increased risk for the development of Crohn's disease and with a more severe disease course. Combining information from the known common risk polymorphisms may enable clinicians to predict the course of Crohn's disease.

Eshuis EJ, Bemelman WA, van Bodegraven AA, Sprangers MA, Bossuyt PM, van Milligen de Wit AW, Crolla RM, Cahen DL, Oostenbrug LE, Sosef MN, Voorburg AM, Davids PH, van der Woude CJ, Lange J, Mallant RC, Boom MJ, Lieverse RJ, van der Zaag ES, Houben MH, Vecht J, Pierik RE, van Ditzhuijsen TJ, Prins HA, Marsman WA, Stockmann HB, Brink MA, Consten EC, van der Werf SD, Marinelli AW, Jansen JM, Gerhards MF, Bolwerk CJ, Stassen LP, Spanier BW, Bilgen EJ, van Berkel AM, Cense HA, van Heukelem HA, van de Laar A, Slot WB, Eijsbouts QA, van Ooteghem NA, van Wagensveld B, van den Brande JM, van Geloven AA, Bruin KF, Maring JK, Oldenburg B, van Hillegersberg R, de Jong DJ, Bleichrodt R, van der Peet DL, Dekkers PE, Goei TH, Stokkers PC. · Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. · BMC Surg. · Pubmed #18721465 links to  free full text

Abstract: BACKGROUND: With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction.The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs. METHODS/DESIGN: The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007. DISCUSSION: The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease. TRIAL REGISTRATION: Nederlands Trial Register NTR1150.

Koelewijn CL, Schwartz MP, Samsom M, Oldenburg B. · Department of Gastroenterology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. · World J Gastroenterol. · Pubmed #18176967 links to  free full text

Abstract: AIM: To explore if C-reactive protein (CRP) levels might serve as a prognostic factor with respect to the clinical course of Crohn's disease and might be useful for classification. METHODS: In this retrospective cohort study we enrolled 94 patients from the inflammatory bowel disease (IBD) database of the University Medical Centre Utrecht. CRP levels during relapse were correlated with the number of relapses per year. Severity of relapses was based on endoscopic reports and prednisone use. Furthermore, patients were categorized in a low or high CRP group based on their CRP response during relapse and demographic and clinical features were compared. RESULTS: Overall, a positive correlation between CRP levels, number of relapses, and severity of relapse was found (respectively rs = 0.31, P < 0.01 and rs = 0.50, P < 0.001). Employing a cut-off level of 15 mg/L, the index CRP level was found to discriminate patients with respect to the number of relapses per year, as well as for severity of relapses (respectively 0.25 +/- 0.16 vs 0.36 +/- 0.24, P < 0.05 and 4.4 +/- 1.2 vs 3.2 +/- 1.1 on a 10-point visual analogue scale, P < 0.001 for the high CRP and low CRP groups respectively). In addition, the high CRP group showed more cumulative days of prednisone use per year (107 +/- 95 vs 58 +/- 48, P < 0.05), as well as a better response to infliximab (93 % vs 33 %, P = 0.06). CONCLUSION: A higher CRP level during relapse seems to be associated with a more severe clinical course of disease.

Minderhoud IM, Oldenburg B, Schipper ME, ter Linde JJ, Samsom M. · Department of Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands. · Clin Gastroenterol Hepatol. · Pubmed #17481962 No free full text.

Abstract: BACKGROUND & AIMS: Symptoms resembling irritable bowel syndrome (IBS) are reported frequently in Crohn's disease (CD) patients in remission. Studies of the mucosal content of serotonin, which is a pivotal neurotransmitter in the gut, suggest that serotonin availability is altered in IBS patients. We aimed to study the role of serotonin in the generation of IBS-like symptoms in CD patients in remission. METHODS: Ileal and colonic biopsy specimens were obtained from 20 CD patients in remission, 10 with and 10 without IBS-like symptoms, and 11 healthy controls. Enterochromaffin cells were counted, and messenger RNA expression levels of tryptophan hydroxylase (TpH)-1 and serotonin reuptake transporter were determined. RESULTS: The levels of mucosal serotonin reuptake transporter expression were significantly higher in the ileum than in the colon, in all groups studied (P < .02). When the ileum and colon were analyzed separately, TpH-1 expression in the colon of CD patients with IBS-like symptoms was found to be significantly higher compared with the 2 other studied groups (controls, P < .005; CD patients without IBS-like symptoms, P < .01). The number of enterochromaffin cells per gland was comparable for the patient groups in the ileum and colon. CONCLUSIONS: CD patients in remission who experience IBS-like symptoms have increased mucosal TpH-1 levels in the colon, suggesting that increased serotonin biosynthesis in the colon plays a role in the generation of the symptoms.

Minderhoud IM, Samsom M, Oldenburg B. · Department of Gastro-enterology, Univerisity Medical Centre Utrecht, Utrecht, The Netherlands. · World J Gastroenterol. · Pubmed #17465453 links to  free full text

Abstract: AIM: To study the effect of infliximab on fatigue in relation to cytokine levels in Crohn's disease (CD) patients. METHODS: Fourteen CD patients were blinded for treatment and received placebo at baseline, and infliximab 2 wk later, with a follow-up of 4 wk. Blood samples were drawn on a regular basis, and questionnaires on fatigue, depression, quality of life, and clinical disease activity were completed at regular intervals. RESULTS: After placebo infusion, fatigue scores decreased within 3 d (3.5 points +/- 1.1, P <or= 0.01), but returned to baseline values 14 d after this infusion. The drop of fatigue scores following infliximab infusion sustained until the end of the study (3.8 points +/- 1.4, P <or= 0.05). Quality of life was increased at the end of the study compared to baseline values (138.6 +/- 9.4 vs 179.4 +/- 6.7; P <or= 0.005), whereas depression scores were decreased (20.4 +/- 9.4 vs 11.3 +/- 2.2; P <or= 0.01). No correlation between the severity of fatigue and the level of cytokines was observed. CONCLUSION: The reduction of fatigue after infliximab infusion is subjective to a placebo effect. The effect of infliximab on fatigue, however, persists while the placebo effect disappears after a short period of time. A clear role of cytokines could not be substantiated.

Reinisch W, Hommes DW, Van Assche G, Colombel JF, Gendre JP, Oldenburg B, Teml A, Geboes K, Ding H, Zhang L, Tang M, Cheng M, van Deventer SJ, Rutgeerts P, Pearce T. · Universitaetsklinik Innere Medizin IV, Abteilung Gastroenterologie and Hepatologie, Vienna, Austria. · Gut. · Pubmed #16492717 No free full text.

Abstract: INTRODUCTION: This study was designed to evaluate the safety of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease (CD). PATIENTS AND METHODS: Forty five patients with a CD activity index (CDAI) of 250-450 were randomised in a double blind, placebo controlled, dose escalating fashion to receive single doses of fontolizumab (0.1, 1.0, and 4.0 mg/kg) or placebo. By day 29, patients with clinical response were re-randomised to receive three additional doses of one half their initial fontolizumab dose or placebo at four weekly intervals. Primary objectives were safety and tolerability. Secondary outcomes included assessments of immunogenicity, clinical activity, and potential pharmacodynamic surrogates. RESULTS: Treatment was generally well tolerated. There were slightly more reports of chills, flu-like syndrome, asthenia, nausea, and vomiting in the 1.0 mg and 4.0 mg/kg fontolizumab cohorts. Two serious adverse events rated as worsening of CD occurred under fontolizumab. Antibodies to fontolizumab were confirmed in one patient. No differences in clinical activity parameters were noted between any of the active treatment groups and placebo, with the placebo group having a particularly favourable outcome (60% response and 40% remission). By day 29, a more enhanced decrease in median Crohn's disease endoscopic index of severity (p = 0.02) and serum C reactive protein (p<0.001) was observed in the 4.0 mg/kg (n = 14) fontolizumab cohort compared with placebo (n = 10). Pharmacodynamic effects were observed by immunohistochemistry. CONCLUSIONS: Fontolizumab was well tolerated with minimal immunogenicity at doses of up to 4.0 mg/kg in patients with CD. A biological activity of fontolizumab is suggested.

Minderhoud IM, Oldenburg B, Wismeijer JA, van Berge Henegouwen GP, Smout AJ. · Department of Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands. · Dig Dis Sci. · Pubmed #15139501 No free full text.

Abstract: The aim of this study was to assess the prevalence of irritable bowel syndrome-like symptoms in healthy controls and inflammatory bowel disease patients in remission using the Rome II criteria. Furthermore, the possible relation of irritable bowel syndrome-like symptoms with the quality of life and coping behavior was studied. Seventy-three ulcerative colitis patients in remission, 34 Crohn's disease patients in remission, and 66 healthy controls completed questionnaires on irritable bowel syndrome, quality of life, and coping. Using the Rome II criteria, irritable bowel syndrome-like symptoms were found in one-third of ulcerative colitis patients and in 42% of Crohn's disease patients in remission. The presence of irritable bowel syndrome-like symptoms impaired the quality of life of patients, while no relation was found between the presence of symptoms and coping strategies.

Oldenburg B, van Kats-Renaud H, Koningsberger JC, van Berge Henegouwen GP, van Asbeck BS. · Department of Gastroenterology, University Medical Center, Heidelberglaan 100, Room number F02.618, 3584 CX Utrecht, The Netherlands. · Clin Chim Acta. · Pubmed #11498080 No free full text.

Abstract: BACKGROUND: Reactive oxygen species (ROS) are produced in excess in the inflamed mucosa and peripheral blood of patients with inflammatory bowel disease. These species have emerged as a common pathway of tissue injury in a wide variety of inflammatory and other disease processes. The present study was conducted to assess ROS production and to correlate this with parameters of inflammatory activity. METHODS: In 25 patients with Crohn's disease (CD), 20 patients with ulcerative colitis (UC) and 65 age- and sex-matched healthy volunteers ROS production was measured using the whole blood luminol enhanced chemiluminescence assay (LECA). Disease activity was assessed using the Crohn's disease activity index and the Ulcerative Colitis Symptoms Score (UCSS) for CD and UC, respectively. Furthermore, the effect of various scavengers, enzymes and enzyme inhibitors on LECA was studied to assess the contribution of different ROS. RESULTS: LECA was significantly higher in CD and UC patients compared with healthy controls (7.1+/-4.7 and 9.8+/-6 vs. 5.2+/-2.8 x 10(3) counts per minute (cpm), p<0.05 and <0.001). In CD, relative LECA (patient/control) was correlated with the Crohn's disease activity index and C-reactive protein (CRP) (r=0.54, p=0.001 and r=0.51, p=0.01). In UC, CRP but not LECA was correlated with the Ulcerative Colitis Symptoms Score (C-reactive protein: r=0.42, p=0.01). Addition of azide, superoxide dismutase, deferoxamine and dimethylthiourea resulted in a decrease of LECA values. CONCLUSION: Whole blood LECA is increased in patients with CD and UC. This parameter is correlated with disease activity in CD. The observed chemiluminescence is probably due to generation of superoxide and the hydroxyl radical.

Oldenburg B, Fijnheer R, van der Griend R, vanBerge-Henegouwen GP, Koningsberger JC. · Department of Gastroenterology, University Medical Center, Utrecht, The Netherlands. · Am J Gastroenterol. · Pubmed #11051355 No free full text.

Abstract: OBJECTIVE: Patients with inflammatory bowel disease (IBD) are at increased risk for thromboembolic events. Hyperhomocysteinemia, which is an established risk factor for arterial as well as venous thrombosis, may be more prevalent in IBD because of vitamin deficiencies. METHODS: In this retrospective study, we studied the concentrations of total homocysteine (tHcy), cobalamin, folate, and pyridoxine in 231 consecutive patients with IBD, of whom 16 patients had a history of venous thrombosis, and nine a history of arterial thrombosis. Age- and gender-matched healthy volunteers served as controls (n = 102). RESULTS: Homocysteine concentrations in patients were higher (12.3 micromol/L [range 4.6-51.3] vs 11.1 micromol/L [range 3.9-27.6], p = 0.001) and hyperhomocysteinemia tended to be more prevalent in patients than in the controls (11.1% vs 5%, p = 0.07). Folate, cobalamin, creatinine, and pyridoxine concentrations were correlated with tHcy. Folate deficiency was infrequently encountered in IBD patients (4.3%). The tHcy concentration in patients with a history of venous or arterial thrombosis was not higher than in patients without a history of thrombosis (12.7 micromol/L [range 4.6-40.1] and 15.2 micromol/L (range 10.5-26.8) vs 12.3 micromol/L [range 10.5-26.8], not significant). Hyperhomocysteinemia was found in 18.8% of the patients with venous thrombosis, 11.1% of the patients with arterial thrombosis, and 10.5% of the patients without thrombosis (not significant). CONCLUSIONS: Hyperhomocysteinemia is a common phenomenon in IBD and correlates with serum folate, cobalamin, creatinine, and pyridoxine concentrations. No correlation between tHcy and a history of venous or arterial thromboembolic complications is found. Hyperhomocysteinemia does not seem to be a major contributory factor in the development of venous or arterial thrombosis in IBD patients.

Verburg R, Zelissen P, Rothova A, Siersema PD, Oldenburg B. · No affiliation provided · Inflamm Bowel Dis. · Pubmed #18383178 No free full text.

This publication has no abstract.

Oldenburg B. · No affiliation provided · Ned Tijdschr Geneeskd. · Pubmed #17929719 No free full text.

This publication has no abstract.