Christian von Tirpitz

Validation of the EuroQol questionnaire in patients with inflammatory bowel disease.

Objective The EuroQol EQ-5D is a generic questionnaire for describing and valuing patients’ health-related quality of life. The purpose of the study was to analyse the construct validity, criterion validity, test–retest reliability and responsiveness of the EQ-5D in patients with inflammatory bowel disease. Methods 152 consecutive patients with inflammatory bowel disease (123 with Crohns disease and 29 with ulcerative colitis) completed the EQ-5D, the SF-36 and the Inflammatory Bowel Disease Questionnaire (IBDQ). Of the study group, 66 patients filled in the EQ-5D a second time after a 2-week gap, including a transition question. Disease activity was measured by the Crohns Disease Activity Index (CDAI) and by Rachmilewitzs Clinical Activity Index (CAI). Results The EQ-5D showed a moderate ceiling effect. Correlation between the EQ-5D visual analogue scale (EQ VAS) score and CDAI/CAI was rs = −0.65/rs = −0.71 (both P < 0.001). Levels of responses to EQ-5D items and the EQ VAS score were significantly better for patients in remission than for patients with active disease (all P < 0.01). For the total sample, coefficients of correlation between the EQ VAS score and SF-36 and IBDQ scores ranged between 0.37 and 0.73 (all P < 0.0001). When repeated, the EQ-5D was reliable in stable patients (intraclass correlation coefficient for EQ VAS = 0.77, kappa statistic for items 0.39 to 1.00); the EQ VAS was responsive in patients who, in the transition question, indicated an improvement in health state (effect size 0.79). Conclusions The EQ-5D is reasonably valid, reliable and responsive in patients with inflammatory bowel disease. It can be used to generate preference-based valuations of health-related quality of life in inflammatory bowel disease.

Contrast-enhanced wideband harmonic imaging ultrasound (SonoVue®): A new technique for quantifying bowel wall vascularity in Crohn's disease

Objective. To assess the possibility of quantitative determination of bowel wall vascularity using contrast-enhanced (SonoVue®) wideband harmonic imaging ultrasound and the HDI-Lab software in patients with Crohns disease. Material and methods. Twenty-one patients (13 F, 8 M, average age 33.8±12.7 years, range 21–60 years) with histologically confirmed Crohns disease and bowel wall thickness ≥5 mm were recruited for the study. All ultrasound examinations were performed using a Philips HDI 5000 scanner. Bowel wall vascularity was determined at the site of maximum bowel wall thickness at baseline and at 30, 60, 90 and 120 s following application of the contrast enhancer SonoVue (1.2 ml) using the HDI-Lab software. Results. The mean length of bowel segments exhibiting increased wall thickness was 122.3 mm (range: 23–350±74.7 mm), with a mean wall thickness of 7.6±1.2 mm. Onset of echo enhancement secondary to contrast medium application was observed after an average 13.4 s (range 7–19±4.2 s). Echo intensity corresponding to maximum vascularity was measured 30 s after application of contrast medium. Maximum average contrast medium uptake was 217.5% (range 118–466±100.1%). Conclusions. It is possible to quantify bowel wall vascularity accurately in patients with Crohns disease using contrast-enhanced pulse inversion ultrasound (low-MI).

Cost of outpatient care in patients with inflammatory bowel disease in a German University Hospital

Background and Aim:  Because of its long duration, inflammatory bowel disease (IBD) causes high use of health services and high lifetime costs for medical care. The aim of the present study was to measure the costs of outpatient care in patients with IBD in a German University Hospital and to identify potentially relevant determinants of costs.

Lactose intolerance in active Crohn's disease: clinical value of duodenal lactase analysis.

Background Patients with active Crohns disease (CD) often report having abdominal symptoms after ingestion of milk products, but the pathomechanism for lactose malabsorption seems to be complex. Goals To investigate the prevalence of clinical milk intolerance and to objectify symptoms with hydrogen (H 2 ) breath testing, analysis of lactase protein, and enzyme activity in the duodenal mucosa in patients with CD and in healthy controls. Study In 49 patients with CD and 24 controls, H 2 breath testing was performed. All individuals underwent endoscopy of the upper gastrointestinal tract, in which multiple pinch samples were taken from the distal duodenum. Lactase activity was measured using the method of Dahlquist. The lactase protein expression was analyzed by gel electrophoresis using the monoclonal antibody mlac 10 and by immunochemistry using the monoclonal antibody mlac 4. Results Prevalence of milk intolerance in healthy controls was 16.6% versus 46.9% in patients with CD, with a high frequency (83.3%) in patients with active disease (CD activity index >150). Milk intolerance was correlated to the duration of inflammatory bowel disease (p = 0.023) but not to the location or previous bowel resection. Hydrogen breath testing had a moderate sensitivity in detecting lactose maldigestion (70.4%) and a high specificity (95.6%). Duodenal lactase levels were also correlated to disease activity, whereas correlations to clinical symptoms remained poor. Patients with milk intolerance had a significantly reduced bone density at the lumbar spine (z-score, −1.33 ± 0.92 vs. −0.19 ± 0.95 [mean ± SD];p = 0.002) Conclusions Milk intolerance is a frequent problem in active CD, which can be objectified accurately by H 2 lactose breath testing. Decreased lactase levels in the duodenal mucosa may be found during an acute flare but are not the predominant cause of milk intolerance in CD.

Extracorporeal photopheresis (ECP) in patients with steroid-dependent Crohn's disease: An open-label, multicenter, prospective trial

Background:Extracorporeal photopheresis (ECP) involves ex vivo leukocyte treatment with methoxsalen and UVA light to generate a tolerogenic response. A previous trial demonstrated that ECP permits corticosteroid withdrawal in steroid-dependent Crohns disease (CD) patients who were in clinical remission. We studied the effect of ECP on steroid withdrawal in steroid-dependent CD. Methods:Patients with CD for ≥6 months, in remission at baseline while on steroids, but who had failed at ≥1 steroid withdrawal were included. Patients received two ECP treatments every 2 weeks for the 24-week steroid tapering period and underwent steroid-tapering. Patients completing steroid tapering could receive maintenance ECP (two treatments/week) every month for 24 weeks. Results:Thirty-one patients (Crohns Disease Activity Index [CDAI] score 91; Inflammatory Bowel Disease Questionnaire [IBDQ] 172.5) were enrolled (baseline corticosteroid dose, 20 mg/day); 65% were refractory to/intolerant of anti-tumor necrosis factor (TNF) agents or immunosup-pressants. After 24 weeks of ECP, 7 of 31 (22.6%) patients discontinued steroids while maintaining a CDAI of <150. At week 24, the steroid dose for the remaining patients on corticosteroids was 10 mg (P < 0.003 vs. baseline) with a CDAI of 110 and an IBDQ of 179. Following maintenance treatment, three patients remained in steroid-free remission. The 10 patients in the study and receiving ECP at week 48 had a steroid dose of 3.5 mg with a CDAI of 40 and an IBDQ of 188. Conclusions:ECP permitted discontinuation or reduction of steroids in a population of refractory steroid-dependent CD patients. ECP may be useful in permitting steroid withdrawal in selected steroid-dependent CD patients. Ideally, these results need to be confirmed in a “sham-controlled” clinical trial.

Extracorporeal photopheresis for the treatment of refractory Crohn's disease: Results of an open-label pilot study

Background: Extracorporeal photopheresis (ECP) is effective in immune‐mediated disorders. A prospective, uncontrolled pilot study was conducted to evaluate the safety and efficacy of ECP in patients with active Crohns disease (CD) who were refractory to or intolerant of immunosuppressants and/or anti‐TNF therapies. Methods: Patients with moderate‐to‐severely active CD (Crohns Disease Activity Index [CDAI] 220–450 points) underwent 12 weeks of ECP treatment (Weeks 1–4: twice weekly, every week; Weeks 5–12: twice weekly, every other week). Clinical response was defined as a decrease in the CDAI of ≥100 points or remission (CDAI <150 points) at Week 12. Patients who responded at Week 12 could receive an additional 12 weeks of ECP treatment (twice weekly, every other week) in an extension study. Results: Twenty‐eight patients were enrolled with a mean baseline CDAI score of 314 (range 207–457). At Week 12, 14 patients (50%) responded; 13 patients responded within 6 weeks. Seven patients (25%) attained remission by Week 12. Three of 5 patients with open fistulae at baseline had fistula closure. Response was similar among patients naïve to anti‐TNF agents and patients who had previously been refractory or intolerant to anti‐TNF agents. Of the 12 patients who entered the extension study, 9 (75%) maintained their response at Week 24. Conclusions: In patients with moderate‐to‐severely active CD who were refractory to or intolerant of immunosuppressants and/or anti‐TNF agents, ECP was well tolerated and induced clinical response (50%) and remission (25%) in patients. Most patients were able to maintain a response with continued treatments.

Messung der ambulanten Behandlungskosten von chronisch entzündlichen Darmerkrankungen an einer deutschen Universitätsklinik

ZusammenfassungZiel: Gesundheitsökonomische Betrachtung der Versorgung von Patienten mit chronisch entzündlichen Darmerkrankungen und Entwicklung eines Konzeptes zur Kostenmessung der ambulanten Behandlung dieser Patienten an einem deutschen Universitätsklinikum. Material und Methodik: Die Messung der Versorgungsleistungen erfolgte auf Grundlage einer computergestützten, routinemäßig geführten Datenbank der Ambulanz der Medizinischen Klinik. Bei der Kostenerhebung wurde schrittweise vorgegangen: 1. Identifizierung der Kategorien des Ressourcenverbrauchs, 2. mengenmäßige Messung der verbrauchten Ressourcen und 3. monetäre Bewertung der diagnostischen und therapeutischen Leistungen auf Basis von Gebührenordnungen und Arzneimittelpreisen. Ergebnisse: Die Interventionen und Versorgungsleistungen von 272 Patienten mit einer mindestens 1-jährigen Behandlungsdauer in der CED-Spezialambulanz wurden strukturiert erfasst. Folgende Kategorien des Ressourcenverbrauchs konnten identifiziert und mengenmäßig bestimmt werden: ärztliche Anamnese und Untersuchung bei 100% der Besuche, Labordiagnostik bei 87,1%, endoskopische bzw. sonographische Leistungen bei 36,9%, radiologische Maßnahmen bei 14,1%. Eine medikamentöse Therapie erfolgte in 93,6% der Fälle. Die jährlichen Gesamtkosten der Versorgung durch die Klinikambulanz beliefen sich je Patient auf 3 171 Euro, wobei ca 85% auf die medikamentöse Versorgung entfielen. Bei den Kosten der medikamentösen Behandlung stand die Therapie mit Mesalazin an erster Stelle (48%), gefolgt von Budesonid (15%). Schlussfolgerung: Das vorgestellte Kostenmesskonzept ermöglicht die Berechnung von Kosten der ambulanten Behandlung von Patienten mit chronisch entzündlichen Darmkerkrankungen. Es ist geeignet für den Einsatz in der ökonomischen Evaluation zur Berechnung der Kosten von alternativen Behandlungen oder von diagnostischen Strategien, die im Rahmen eines ambulanten Settings in einer Klinik durchgeführt werden. Darüber hinaus kann es als Komponente in Krankheitskostenstudien Verwendung finden. Bei einer Ü,bertragung des Konzeptes auf andere Kliniken muss geprüft werden, ob die erforderlichen Leistungsdaten routinemäßig dokumentiert werden. Zur Erstellung der ökonomischen Indikatoren ist gegebenenfalls eine weitere Datenaufbereitung notwendig.AbstractObjective: To create a concept for measuring and valuating resource utilization of outpatient treatment of patients with inflammatory bowel disease in a German university hospital. Material and Methods: The measurement of health services was achieved using a computer-based routinely administered data base of the Medical Department. Measuring costs was performed in three steps: 1. identification of the categories of resource utilization, 2. quantitative measurement of resource use, 3. monetary valuation of the utilization of resources using German fee schedules and prices for drugs. Results: The resource utilization of 272 patients with a treatment period of more than 1 year could be identified in a structured form. Categories of resource use could be identified and quantitatively measured as follows: anamnesis and physical examination by a physician in 100% of the visits, laboratory test in 87.1%, endoscopic or sonographic services in 36.9%, and radiologic procedures in 14.1%. In 93.6% of the visits a medication was prescribed. Annual costs of outpatient care provided by the hospital were 3,171 Euro per patient. Medication accounted for 85% of total costs. Analyzing the costs of medical treatment, mesalazine was the major cost component (48%), followed by budesonide (15%). Conclusion: The presented concept offers a good access to measure costs of outpatient treatment of patients with inflammatory bowel disease. It is suitable for measuring costs in the economic evaluation of alternative treatments or diagnostic strategies in an outpatient setting. It furthermore may be used as a component in cost-of-illness studies. For transferring the concept to other hospitals, the availability of a routine documentation of services should be checked. For economic analysis, a further data management is required.

Bones and Crohn’s: No benefit of adding sodium fluoride or ibandronate to calcium and vitamin D

AIM To compare the effect of calcium and cholecalciferol alone and along with additional sodium fluoride or ibandronate on bone mineral density (BMD) and fractures in patients with Crohns disease (CD). METHODS Patients (n =148) with reduced BMD (T-score < -1) were randomized to receive cholecalciferol (1000 IU) and calcium citrate (800 mg) daily alone(group A, n = 32) or along with additional sodium fluoride (25 mg bid) (group B, n = 62) or additional ibandronate (1 mg iv/3-monthly) (group C, n = 54). Dual energy X-ray absorptiometry of the lumbar spine (L1-L4) and proximal right femur and X-rays of the spine were performed at baseline and after 1.0, 2.25 and 3.5 years. Fracture-assessment included visual reading of X-rays and quantitative morphometry of vertebral bodies (T4-L4). RESULTS One hundred and twenty three (83.1%) patients completed the first year for intention-to-treat (ITT) analysis. Ninety two (62.2%) patients completed the second year and 71 (47.8%) the third year available for per-protocol (PP) analysis. With a significant increase in T-score of the lumbar spine by +0.28 ± 0.35 [95% confidence interval (CI): 0.162-0.460, P < 0.01], +0.33 ± 0.49 (95% CI: 0.109-0.558, P < 0.01), +0.43 ± 0.47 (95% CI: 0.147-0.708, P < 0.01) in group A, +0.22 ± 0.33 (95% CI: 0.125-0.321, P < 0.01); +0.47 ± 0.60 (95% CI: 0.262-0.676, P < 0.01), +0.51 ± 0.44 (95% CI: 0.338-0.682, P < 0.01) in group B and +0.22 ± 0.38 (95% CI: 0.111-0.329, P < 0.01), +0.36 ± 0.53 (95% CI: 0.147-0.578, P < 0.01), +0.41 ± 0.48 (95% CI: 0.238-0.576, P < 0.01) in group C, respectively, during the 1.0, 2.25 and 3.5 year periods (PP analysis), no treatment regimen was superior in any in- or between-group analyses. In the ITT analysis, similar results in all in- and between-group analyses with a significant in-group but non-significant between-group increase in T-score of the lumbar spine by 0.38 ± 0.46 (group A, P < 0.01), 0.37 ± 0.50 (group B, P < 0.01) and 0.35 ± 0.49 (group C, P < 0.01) was observed. Follow-up in ITT analysis was still 2.65 years. One vertebral fracture in the sodium fluoride group was detected. Study medication was safe and well tolerated. CONCLUSION Additional sodium fluoride or ibandronate had no benefit over calcium and cholecalciferol alone in managing reduced BMD in CD.

Cost Effectiveness of Ibandronate for the Prevention of Fractures in Inflammatory Bowel Disease-Related Osteoporosis : Cost-Utility Analysis Using a Markov Model

BackgroundOsteoporosis is a frequent complication in patients with inflammatory bowel disease. Recent studies have shown bisphosphonates to considerably reduce fracture risk in patients with osteoporosis, and preventing fractures with bisphosphonates has been reported to be cost effective in older populations. However, no studies of the cost effectiveness of these agents in preventing fractures in patients with inflammatory bowel disease are available.ObjectiveTo investigate the cost effectiveness of the bisphosphonate ibandronate combined with calcium/colecalciferol (‘ibandronate’) in patients with osteopenia or osteoporosis due to inflammatory bowel disease in Germany. Treatment strategies used for comparison were sodium fluoride combined with calcium/colecalciferol (‘fluoride’) and calcium/colecalciferol (‘calcium’) alone.Study design and methodsA cost-utility analysis was conducted using data from a randomized controlled trial (RCT). Changes in bone mineral density (BMD) were adjusted and predicted for a standardized population receiving each respective treatment. A Markov model was developed, with probabilities of transition to fracture states consisting of BMD-dependent and -independent components. The BMD-dependent component was assessed using predicted change in BMD from the RCT. The independent component captured differences in bone quality and micro-architecture resulting from prevalent fractures or treatment with anti-resorptive drugs.The analysis was conducted for a population with a mean age of the RCT patients (women aged 36 years, men aged 38 years) with osteopenia (T-score about -2.0 at baseline), a population of the same age with osteoporosis (T-score of -3.0 at baseline) and for an older population (both sexes aged 65 years) with osteoporosis (T-score of -3.0). Outcomes were measured as costs per QALY gained from a societal perspective. The treatment duration in the RCT was 42 months. A 5-year period was assumed to follow, during which the treatment effects linearly declined to 0. The simulation time was 10 years.Prices for medication and treatment were presented as year 2004 values; costs and effects were discounted at 5%. To test the robustness of the results, univariate and probabilistic sensitivity analyses (Monte Carlo simulation) were conducted.ResultsThe calcium strategy dominated the fluoride strategy. When the ibandronate strategy was compared with the calcium strategy, the base-case cost-effectiveness ratios (costs per QALY gained) were between €407 375 for an older female population with osteoporosis and €6 516 345 for a younger female population with osteopenia. Univariate sensitivity analyses resulted in variations between 4% of base-case results and dominance of calcium. In Monte Carlo simulations, conducted for the various populations, the probability of an ICER of ibandronate below €50 000 per QALY was never greater than 20.2%.ConclusionThe ibandronate strategy is unlikely to be considered cost effective by decision makers in men or women with characteristics of those in the target population of the RCT, or in older populations with osteoporosis.

Osteoporosis and Other Extraintestinal Symptoms and Complications of Inflammatory Bowel Diseases

Patients with Crohn’s disease and ulcerative colitis are confronted with a wide range of extraintestinal symptoms and complications of their disease. Some of these symptoms can occur even before clinical manifestation of the inflammatory bowel disease. Some of the symptoms (e.g. arthralgia) respond to the therapy of Crohn’s disease or ulcerative colitis, whereas other (e.g. PSC, primary sclerosing cholangitis) can progress even after colectomy. Extraintestinal manifestations are especially common when the colon is inflamed. Crohn’s disease patients with small bowel involvement have significantly less extraintestinal manifestations compared to patients with involvement of the colon [1] (table 1). Furthermore, we can distinguish between extraintestinal manifestations (arthralgia/arthritis, skin manifestations, ocular manifestations, primary sclerosing cholangitis) and secondary complications of the disease (osteoporosis, gallstones, kidney stones, coagulation abnormalities) (fig. 1). In this review, we will focus on the problem of osteoporosis in patients with inflammatory bowel disease and review the current knowledge of extraintesitnal manifestations and complications in IBD.