Crohn Disease: Fleig WE

Fleig WE, Anonymous00108. · Klinik und Poliklinik Innere Medizin I, Universitätsklinikum Kröllwitz, Halle. · Z Gastroenterol. · Pubmed #12541172 No free full text.

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Stange EF, Schreiber S, Fölsch UR, von Herbay A, Schölmerich J, Hoffmann J, Zeitz M, Fleig WE, Buhr HJ, Kroesen AJ, Moser G, Matthes H, Adler G, Reinshagen M, Stein J, Anonymous00103. · Abteilung Innere Medizin 1, Robert-Bosch-Krankenhaus, Stuttgart. · Z Gastroenterol. · Pubmed #12541167 No free full text.

This publication has no abstract.

Fleig WE. · Klinik und Poliklinik für Innere Medizin I, Martin-Luther-Universität Halle-Wittenberg. · Med Klin (Munich). · Pubmed #10194944 No free full text.

Abstract: The antiinflammatory drug 5-aminosalicylic acid is available either as mesalamine in various slightly different galenic preparations or as a prodrug with 5-ASA bound to a carrier molecule as inert as possible, which releases 5-ASA via bacterial degradation in the ileocolon. Data from therapeutic trials in patients with Crohn's disease are only available for mesalamine and sulfasalazine. In active Crohn's disease, high-dose (> 3 g per day) mesalamine only is more effective than placebo, but inferior to systemic steroids. They may be used in patients refusing treatment with classical steroids or not tolerating them if this does not make a case for budesonide. The therapeutic gain of mesalamine over placebo for the prevention recurrence in patients who have reached remission by drug treatment is marginal. Thus, its use in this clinical situation is not appealing. Results for the maintenance of a surgically induced remission appear slightly better so that the use of > 3 g of mesalamine per day may be still justified in this scenario. It is an unresolved question whether the clinical efficacy of different galenic mesalamine prepations in maintaining postoperative remission varies with the preoperative disease location. Present data are not sufficient to support differential drug treatment based on this parameter.

Lochs H, Mayer M, Fleig WE, Mortensen PB, Bauer P, Genser D, Petritsch W, Raithel M, Hoffmann R, Gross V, Plauth M, Staun M, Nesje LB. · IV Medizinische Klinik, Universitätsklinikum Charité, Humboldt Universität, Berlin, Germany. · Gastroenterology. · Pubmed #10648454 No free full text.

Abstract: BACKGROUND & AIMS: This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection. METHODS: In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model. RESULTS: Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003). CONCLUSIONS: Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.

Albert JG, Kotsch J, Köstler W, Behl S, Kaltz B, Bokemeyer B, Dollinger MM, Haerting J, Fleig WE. · Universitätsklinik und Poliklinik für Innere Medizin I, Martin-Luther-Universität, Halle. · Z Gastroenterol. · Pubmed #18253897 No free full text.

Abstract: BACKGROUND: The course of Crohn's disease prior to the establishment of the diagnosis is widely unknown. Therefore, we instigated a survey amongst newly diagnosed patients. PATIENTS AND METHODS: Patients diagnosed with CD less than 12 months before enrollment were included. Data on demography, social status, time interval to diagnosis, symptoms, and health care service use were collected in a retrospective, web-based, census. Patients were contacted in cooperation with two organizations: a German patients' organization (Deutsche Morbus Crohn/Colitis ulcerosa Vereinigung e.V. [DCCV]) and a professional organization of German gastroenterologists (Berufsverband der Niedergelassenen Gastroenterologen Deutschlands e.V. [bng]). Study participation was anonymous by use of a transaction number. RESULTS: The median interval period between onset of first symptoms and diagnosis was 13 months. During this time, participants reported having five doctor consultations on average, with 44% of them having a mean of 1.5 hospitalizations. 65% were unfit for work with a 14 day median (2 to 480 days) due to their symptoms. A mean (+/-SD) of 8.6 (+/-7.1) diagnostic tests were performed before the diagnosis was established. Overall health state was judged as temporarily bad or very bad by 84% of the participants. Age at diagnosis, characteristic symptoms, and localization of the disease for the participants did not differ from previously reported international data. DISCUSSION: This web-based survey shows a substantial time interval of over one year until diagnosis of Crohn's disease amongst the study participants. This period is characterized by both psychological stress and impaired ability to work.

Albert JG, Martiny F, Krummenerl A, Stock K, Lesske J, Göbel CM, Lotterer E, Nietsch HH, Behrmann C, Fleig WE. · First Department of Medicine, Martin-Luther-University Hospital and Clinics, D-06097 Halle (Saale), Germany. · Gut. · Pubmed #16020490 links to  free full text

Abstract: BACKGROUND AND AIMS: The diagnostic yield of capsule endoscopy (CE) compared with magnetic resonance imaging (MRI) in small bowel Crohn's disease is not well established. We prospectively investigated CE, MRI, and double contrast fluoroscopy in patients with suspected small bowel Crohn's disease. METHODS: Fifty two consecutive patients (39 females, 13 males) were investigated by MRI, fluoroscopy and--if bowel obstruction could be excluded--by CE. In 25, Crohn's disease was newly suspected while the diagnosis of Crohn's disease (non-small bowel) had been previously established in 27. RESULTS: Small bowel Crohn's disease was diagnosed in 41 of 52 patients (79%). CE was not accomplished in 14 patients due to bowel strictures. Of the remaining 27 patients, CE, MRI, and fluoroscopy detected small bowel Crohn's disease in 25 (93%), 21 (78%), and 7 (of 21; 33%) cases, respectively. CE was the only diagnostic tool in four patients. CE was slightly more sensitive than MRI (12 v 10 of 13 in suspected Crohn's disease and 13 v 11 of 14 in established Crohn's disease). MRI detected inflammatory conglomerates and enteric fistulae in three and two cases, respectively. CONCLUSION: CE and MRI are complementary methods for diagnosing small bowel Crohn's disease. CE is capable of detecting limited mucosal lesions that may be missed by MRI, but awareness of bowel obstruction is mandatory. In contrast, MRI is helpful in identifying transmural Crohn's disease and extraluminal lesions, and may exclude strictures.

Herrlinger KR, Fellermann K, Fischer C, Kreisel W, Deibert P, Schoelmerich J, Fleig WE, Ruhl A, Reinshagen M, Greinwald R, Stange EF, Schwab M. · Department of Gastroenterology, Hepatology and Endocrinology, Robert-Bosch-Hospital, Stuttgart, Germany. · Aliment Pharmacol Ther. · Pubmed #15191508 links to  free full text

Abstract: BACKGROUND: 6-Thioguanine-nucleotides seem to be the active metabolites of thiopurine therapy, and their monitoring has been considered a useful tool for optimizing response in inflammatory bowel diseases. Tioguanine (thioguanine) therapy results in much higher levels of 6-thioguanine-nucleotide levels when compared with azathioprine or mercaptopurine. AIM: To elucidate the influence of 6-thioguanine-nucleotide and methylated 6-thioguanine-nucleotide levels under tioguanine on efficacy and toxicity in Crohn's disease. METHODS: 6-Thioguanine-nucleotide and methylated 6-tioguanine-nucleotide levels were measured regularly in 26 Crohn's disease patients treated with tioguanine. Nucleotide levels were related to efficacy and toxicity. RESULTS: 6-Thioguanine-nucleotide levels rose very high [median 1241 pmol/8 x 10(8) red blood cells (range 313-1853)]. Methylated 6-thioguanine-nucleotide levels were detected in all patients [491 pmol/8 x 10(8) red blood cells (154-1775)]. 6-Thioguanine-nucleotide and methylated 6-thioguanine-nucleotide concentrations correlated significantly (r = 0.7, P < 0.0001). Nucleotide levels from patients achieving remission (n = 14) did not differ significantly from non-remitters (n = 12) [6-thioguanine-nucleotide: 1077 (599-2160) vs. 1210 (534-4665); methylated 6-thioguanine-nucleotide: 510 (214-1222) vs. 421 (145-1284)]. One patient with intermediate thiopurine S-methyltransferase activity experienced bone marrow toxicity upon dose escalation parallel with excessively high thioguanine-nucleotide levels. CONCLUSIONS: 6-Thioguanine-nucleotide as well as methylated 6-thioguanine-nucleotide levels under tioguanine therapy were not related to efficacy. This suggests that monitoring of 6-thioguanine-nucleotide levels is not a useful tool to predict response to thiopurines.

Herrlinger KR, Kreisel W, Schwab M, Schoelmerich J, Fleig WE, Ruhl A, Reinshagen M, Deibert P, Fellermann K, Greinwald R, Stange EF. · Robert-Bosch-Hospital, Stuttgart, Germany. · Aliment Pharmacol Ther. · Pubmed #12622758 links to  free full text

Abstract: BACKGROUND: : Azathioprine and mercaptopurine are commonly used in chronic active Crohn's disease. They share the disadvantage of a delayed onset of action and potentially serious side-effects, and are metabolized to thioguanine nucleotides which are thought to be the active metabolites. The direct use of 6-thioguanine may offer a more rapid and safer alternative. We conducted an open prospective study to investigate the efficacy and safety of 6-thioguanine in chronic active Crohn's disease. METHODS: : Thirty-seven patients with chronic active Crohn's disease and a Crohn's disease activity index of > 150 were enrolled in this study. Inclusion criteria were steroid dependence (n = 19), steroid refractoriness (n = 9) and/or intolerance (n = 16) or refractoriness (n = 6) to azathioprine. Patients were treated with 40 mg/day of 6-thioguanine for 24 weeks; a dose escalation to 80 mg was allowed at week 12. Remission was defined as a Crohn's disease activity index of < 150 associated with a decrease of > 70 points; response was defined as a decrease of > 70 points in the Crohn's disease activity index. RESULTS: : In the intention-to-treat analysis, 13 of 37 patients achieved remission (35%). Twelve of these 13 patients achieved remission after 4 weeks. Fifty-seven per cent of patients (21/37) achieved a response. The mean Crohn's disease activity index decreased from 284 +/- 74 to 153 +/- 101. 6-Thioguanine was more effective in azathioprine-intolerant than in azathioprine-refractory patients. Twelve of 16 patients intolerant to azathioprine tolerated 6-thioguanine. Adverse events included phototoxicity, pancreatitis, headache, nausea, alopecia, arthralgia, minor infections and reversible elevation of transaminases. Six patients required discontinuation of medication, two because of leucopenia. CONCLUSIONS: : In this patient group with chronic active Crohn's disease, 6-thioguanine appeared to be effective with acceptable short-term toxicity, but long-term controlled trials are clearly needed to further define its role.