Chronic Active Crohn's Disease Research Articles

Future Therapeutic Approaches for Inflammatory Bowel Diseases

In this review, we speculate about future therapeutic approaches for inflammatory bowel diseases (IBDs), focusing on the need for better preclinical and clinical models and approaches beyond small molecules and systemically administered biologics. We offer ideas to change clinical trial programs and to use immunologic and genetic biomarkers to personalize medicine. We attempt to reconcile past therapeutic successes and failures to improve future approaches. Some of our ideas might be provocative, but we hope that the examples we provide will stimulate discussion about what will advance the field of IBD therapy.

Methotrexate for maintenance of remission in chronic active Crohnʼs disease

According to current guidelines methotrexate (MTX) should be considered as a second-line immunomodulator in patients with chronic active Crohn's disease (CD) if purine analogs are not tolerated or there is a lack of efficacy. However, its therapeutic role remains controversial to the present day. Medical records of all eligible patients treated in the outpatient clinic of the Johann Wolfgang Goethe-University Hospital between December 2000 and January 2009 were reviewed. Sixty-three patients were identified. The mean duration of treatment was 100 weeks (range, 2-364 weeks) with a mean cumulative dose of MTX of 2130 mg (range, 40-9005 mg). In 50 (79%) patients started on MTX clinical remission could be achieved within 3 months of treatment. The cumulative probability of these patients to maintain remission was 95.3%, 89.5%, 70.6%, and 62.8% at 6 months, 1, 2, and 3 years of treatment, respectively. The respective figures of the meta-analysis were 94%, 86%, 75%, 53%, and 43. Drug-related side effects were reported in 50 patients (79%), leading to withdrawal of MTX in 21 cases (33%). Along with previous observations our data demonstrate the efficacy of MTX as a second-line immunomodulator in chronic active CD. However, its use is limited due to intolerable side effects in a large proportion of patients. The results should encourage further research in order to establish the definite significance of MTX in chronic active CD.

6-Thioguanine Nucleotide–Adapted Azathioprine Therapy Does Not Lead to Higher Remission Rates Than Standard Therapy in Chronic Active Crohn Disease: Results from a Randomized, Controlled, Open Trial

A prospective randomized trial in patients with Crohn disease studied whether 6-thioguanine nucleotide (6-TGN) concentration-adapted azathioprine (AZA) therapy is clinically superior to a standard dose of 2.5 mg/kg/day AZA. After 2 weeks of standard therapy, patients (n = 71) were randomized into standard (n = 32) or adapted-dose (n = 25) groups; 14 patients dropped out before randomization. In the adapted group, the AZA dose was adjusted to maintain 6-TGN concentrations between 250 and 400 pmol/8 x 10(8) erythrocytes (Ery). Response criteria were the number of patients in remission after 16 weeks without steroids (primary) and remission after 24 weeks, frequency of side effects, and quality of life (secondary). After 16 weeks, 14 of 32 (43.8%) patients in the standard group vs 11 of 25 (44%) in the adapted group were in remission without steroids (intent-to-treat analysis). After 24 weeks, 43.8% vs 40% were in remission. No significant differences were found concerning quality of life, disease activity, 6-TGN concentrations, AZA dose, or dropouts due to side effects. Sixty-six patients had a wild-type thiopurine S-methyltransferase (TPMT) genotype, with TPMT activities of 8 to 20 nmol/(mL Ery x h). Five patients (dropouts after randomization) were heterozygous, with TPMT activities <8 nmol/(mL Ery x h). 6-Methyl mercaptopurine (6-MMP) concentrations >5700 pmol/8 x 10(8) Ery were not associated with hepatotoxicity. Standard and adapted dosing with the provided dosing scheme led to identical 6-TGN concentrations and remission rates. Adapted dosing had no apparent clinical benefit for patients with TPMT activity between 8 and 20 nmol/(mL Ery x h). Additionally, 6-MMP monitoring had no predictive value for hepatotoxicity.

Tumor Necrosis Factor Blockade: Mechanism of Action

Modulation of the immune response with tumor necrosis factor (TNF) blockers is not a new treatment strategy for many inflammatory disorders; however, relatively little is known about their specific mechanism of action. Understanding the mode of action, pharmacology, and pharmacokinetics of the monoclonal TNF antibodies, infliximab and adalimumab, and the soluble TNF receptor, etanercept, may therefore enable us to account for their differing clinical profiles. The aim of this supplement is to explore the roles and mechanisms of TNF and TNF blockade using in vitro pharmacological and in vivo animal modeling experiments, and in vivo studies of the effects of etanercept on the inflammatory cascade in patients with psoriasis.

Efficacy of mycophenolate mofetil in patients failing 6-mercaptopurine or azathioprine therapy for Crohn's disease

Mycophenolate mofetil (MMF) is a novel immuno-modulator that may be effective in the treatment of chronic active and perianal Crohn's disease (CD). The aim of this study is to assess the efficacy of MMF in CD patients who failed or were intolerant of 6-mercaptopurine (6-MP) or azathioprine (AZA). Eleven CD patients were treated with MMF after a failed course of 6-MP/AZA, and their records reviewed retrospectively. Reasons for 6-MP/AZA intolerance or failure were recorded. Response to MMF was determined by calculation of the Harvey-Bradshaw index and ability to taper steroids. Adverse reactions to MMF were recorded. Eleven patients were identified who failed a previous trial of 6-MP/AZA and other immunomodulators and required immunomodulator therapy. Of 11 patients who started MMF, four had early adverse reactions within 8 weeks and stopped the medication. Of the remaining seven patients who took MMF for at least 8 weeks, one had a complete response, two had a partial response, and four had no response to the medication. In patients who failed 6-MP/AZA, MMF was of benefit in 3 of 11 patients with only one complete responder. This lower-than-expected response rate may indicate that patients who are resistant to 6-MP or AZA may also be resistant to MMF.

Practical guidelines for the treatment of inflammatory bowel disease

In recent years, great progress has been made regarding the treatment of inflammatory bowel disease (IBD), particularly in the field of biological therapies. Nevertheless, the ultimate treatment is not in sight. With the development of new medication, it has become clear that we need a new understanding of IBD. Therapy needs to fit the different subtypes of IBD; e.g. mild disease in comparison to severe chronic active disease or Crohn's disease with or without fistulation or stenosis. The following article gives a practical overview of actual treatments for IBD. The intention of this article is not to provide a complete review of all new scientific developments, but to give a practical guideline for therapy of IBD.

Combining infliximab with methotrexate for the induction and maintenance of remission in refractory Crohn??s disease: a controlled pilot study

Immunosuppression of chronic active Crohn's disease resistant or intolerant to purine antimetabolites still remains a clinical challenge. To obtain long-lasting effects with the anti-TNF-alpha antibody infliximab repeated infusions are often required. Methotrexate has been shown to be a moderately effective drug in maintaining remission in Crohn's disease. The aim of the present pilot study was to evaluate the combination of infliximab and methotrexate as therapy for refractory Crohn's disease. Nineteen patients with chronic active Crohn's disease resistant or intolerant to azathioprine were enrolled. Patients received either two infusions of infliximab (5 mg/kg) alone (n=8) or in combination with long-term methotrexate at a dosage of 20 mg/week (n=11) over 48 weeks. Two out of eight patients receiving infliximab monotherapy and four out of 11 patients treated with infliximab and concomitant methotrexate had discontinued study treatment by week 48, solely because of lack of efficacy. Clinical remission at week 48 was observed in five out of seven patients treated with infliximab and methotrexate, but only in two out of six patients receiving infliximab monotherapy. In addition, patients treated with concomitant methotrexate achieved remission earlier (median time 2 versus 18 weeks) and needed fewer steroids (median prednisolone dose 0 versus 11.8 mg). Despite an increased mean number of adverse events per patient in the methotrexate group, the proportions of patients experiencing any adverse events and serious adverse events were similar across treatment groups. The combination of infliximab with long-term methotrexate may be a promising concept in refractory Crohn's disease. Our data prompt larger trials.

Cyclosporine for induction of remission in Crohn's disease

Cyclosporine was first found to be an effective and well-tolerated immunosuppressive agent in organ transplant recipients, and subsequently in several autoimmune diseases. It was reported in open studies that cyclosporine is effective for induction of remission in Crohn's disease. Four randomized controlled trials have been performed to determine whether the results observed in these open studies were valid. This systematic review summarizes the evidence on the use of oral cyclosporine for the induction of remission in Crohn's disease. To evaluate the effectiveness of oral cyclosporine for induction of remission in patients with active Crohn's disease in the presence and absence of concomitant steroid therapy. Secondary objectives were to evaluate clinical response rates and adverse events associated with cyclosporine. Computer-assisted searches of the on-line bibliographic databases MEDLINE and EMBASE were performed to identify potentially relevant publications between 1980 and July 2004. The MeSH terms "Crohn Disease" or "Inflammatory Bowel disease" and "Cyclosporin" (exploded) were used to perform key word searches of the databases. Manual searches of reference lists from potentially relevant papers were performed in order to identify additional studies that may have been missed. Abstracts from major gastroenterological meetings, The Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register were also searched for relevant studies. Appropriate officials at Sandoz Corporation were contacted to seek information on any unpublished trials. Prospective, randomized, double-blinded, placebo-controlled trials of parallel design with treatment duration of a minimum 12 weeks comparing oral cyclosporine therapy with placebo for treatment of patients with active Crohn's disease were eligible for inclusion. All data were analyzed on an intention-to-treat basis. Data were extracted from the original research articles and converted into 2x2 tables (cyclosporine vs. placebo). Where available, individual 2x2 tables for strata within studies were also used. Heterogeneity was assessed using the chi-square test (p < 0.10 was regarded as statistically significant). For non-pooled data, p-values were derived using the chi-square test. For pooled data, summary test statistics were derived using the Peto odds ratio and 95% confidence intervals. A fixed effects model was used for pooling of data. For continuous data, summary test statistics were derived using the weighted mean difference and 95% confidence intervals. The definitions of treatment success, remission and clinical improvement were set by the authors of each paper, and the data were combined for analysis only if these definitions were sufficiently similar. Brynskov 1989a found that patients receiving high dose cyclosporine (median 7.6 mg/kg/day) had statistically significant clinical improvement at 12 weeks compared to placebo patients. None of the other studies found any statistically significant benefit for clinical improvement or induction of remission for low dose cyclosporine treatment (5 mg/kg/day) used by itself or in combination with corticosteroids compared to placebo. Cyclosporine was associated with a significantly higher proportion of adverse events and withdrawals due to adverse events relative to placebo. Brynskov 1989a enrolled a small number of patients and the modified clinical grading scale used in the study has not been validated in other studies. Furthermore, statistically significant clinical improvement does not imply induction of clinical remission. Indeed, Brynskov 1989a found no statistically significant differences in the mean Crohn's Disease Activity Index score at 12 weeks indicating that cyclosporine was no more effective than placebo for induction of remission in Crohn's disease. The results of this review demonstrate that low dose (5 mg/kg/day) oral cyclosporine is not effective for the induction of remission in Crohn's disease. Patients treated with low dose oral cyclosporine are more likely than placebo treated patients to experience adverse events including renal dysfunction. The use of low dose oral cyclosporine for the treatment of chronic active Crohn's disease does not appear to be justified. Oral dosing at higher levels or parenteral administration of cyclosporine have not been adequately evaluated in controlled clinical trials. Higher doses of cyclosporine are not likely to be useful for the long-term management of Crohn's disease because of the risk of nephrotoxicity and the availability of other proven interventions.

Mesenteric Pulsatility Index Analysis Predicts Response to Azathioprine in Patients with Crohnʼs Disease

Mesenteric blood flow measurement has been found to predict relapse after steroid-induced remission in patients with Crohn's disease (CD) and ulcerative colitis (UC). Therefore, we assessed prospectively the possible relationship between changes in mesenteric blood flow and prognosis in chronically active patients with need of immunosuppressive therapy with azathioprine (AZA) or 6-mercaptopurine (6-MP). Doppler ultrasound (DUS) measurements of the pulsatility index (PI) of the superior mesenteric artery (SMA) and inferior mesenteric artery (IMA) were performed in 52 patients with chronically active inflammatory bowel disease (CD 31 patients; UC 21 patients) before beginning therapy with AZA/6-MP (US1) and during clinical remission (CD activity index <150, Truelove index score I) (US2). Patients were weaned from concomitant therapy with corticosteroids as soon as possible and were followed up for 12 months. After 1 year, 16 patients with CD (51.6%) and 13 patients with UC (61.9%) were in remission, whereas 23 patients had recurrent disease or had undergone surgery. A decreased SMA PI at US2 predicted clinical relapse in all patients with CD [100%; P < 0.001; mean (+/-SD) 77 +/- 67 d after US1], but only 4 of 8 patients (50%; difference not significant; mean 84 +/- 75 d after US1) with UC. Conversely, an increase of SMA PI was associated with sustained remission in the majority of CD patients (12/16 patients; 75%; P < 0.002), but in only 7 of 13 patients (54%) with UC. Flow measurements in the IMA and postprandial values for both arteries were less reliable. Repeated DUS measurements of the SMA PI predict response to AZA/6-MP in patients with chronic active CD.

Remission maintenance by tioguanine in chronic active Crohn's disease.

Tioguanine may offer an alternative for immunosuppression in chronic active Crohn's disease. Recently, we have shown that tioguanine is effective in inducing rapid remission. To evaluate the role of tioguanine in the maintenance of remission in chronic active Crohn's disease. A follow-up study was performed to investigate the long-term efficacy and safety of and tolerance to tioguanine in chronic active Crohn's disease. Sixteen patients who had successfully received 6-tioguanine for remission induction were enrolled. The reasons for immunosuppressive therapy were steroid dependence (n = 10), steroid refractoriness (n = 6) and intolerance (n = 6) or refractoriness (n = 1) to azathioprine. After remission induction therapy for 6 months, patients were treated for another 6 months with a daily dose of 20-40 mg tioguanine. Primary outcomes were remission (Crohn's disease activity index < 150) and complete steroid reduction in steroid-dependent patients at 12 months. Laboratory controls of white blood count and liver enzymes, as well as erythrocyte tioguanine nucleotide levels, were performed regularly. After 12 months of treatment, 14 of 16 (88%) patients were in remission, and 12 of these were completely free of systemic steroids. Adverse events during maintenance therapy included photosensitivity (one patient), minor viral infections (one), headache (four) and mild alopecia (one). One patient developed elevated liver enzymes, splenomegaly and thrombocytopenia, indicative of nodular regenerative hyperplasia of the liver. In responders to tioguanine, the drug appears to be very effective in maintaining remission of chronic active Crohn's disease. Unfortunately, long-term hepatotoxicity seems to be an unpredictable and potentially severe adverse drug reaction. Therefore, to date, tioguanine cannot be recommended for general use outside clinical trials.

6-Thioguanine maintains remission in chronic active Crohn's disease

6-Thioguanine maintains remission in chronic active Crohn's disease

High variation of 6-thioguanine absorption in patients with chronic active Crohn's disease

High variation of 6-thioguanine absorption in patients with chronic active Crohn's disease

Management of Crohn's disease (CD) of the ileoanal pouch with infixinab

Background: 6-Thioguamne (6-TG) may offer an ahernative in immunosuppression for chronic active Crohn's disease (CD) Recently, we showed 6-TG to be rapidly effective in remi~ion induction therapy (Herr/inger etal . , AP&fff in press). To evaluate its role in remission maintenance we conducted a tbilc~w-up study to investigate the long-term efficacy, safety and tolerance of 6-TG in chi'nnic active CD. Patients and Methods: 16 patients who had succes~sb.llly recmved 6-thiognanine tor remission induction were enrolled. Reasons [br immunosuppressiw therapy were steroid-dependency (n = 10), steroid-reti'act oriness (n = 6), and/or intoleance (n = 6) or ret}actoriness (n = 1 ) to azathioprine (Aza), respectively. After the remission induction therapy of six months patients were treated for another st',: months with a &fly dose of 20 to 40rag 6-TG. Primary outcomes were clinical remission (CDAI< 150) and complete steroid-reduction in steroid-dependent patients at month 12. Laboratory controls of white blood count and liver enzymes as well as measurement of erythmcyte 6thioguanine nucleotides (TGN) were performed regulanly Results: Afier 12 months of treatmer~t 14/16 patients were in clinical remission. All but three patients were completely weaned from systemic steroids. At month 12 four of 16 patients were successfnlly switched to ~.a, one patient received methotrexate and relapsed. Three patients refused further treatment and two of them relapsed four months later. Eight patients are still on 6-thiognanine with a daily dose of 10 to 20mg and in remission. Adverse events during maintenance therapy included photosensitivity (n:l), minor viral infections (1), headache (4) and mild alopecia (1) One patient developed elevated liver enzymes, splenomegaly and thrombocytopenia. This patient recovered within 24 weeks after stopping 6-thinguanine. Conclusimrs: 6-Thingnamne appears to be very effective in remission maintanance therapy in chronic active Cmhn's disease Unfortunately', long-term bepatotoxlciy seems to be an unpredictable and potentially severe prohlem Tberetore, fi'om our point of view to date 6-TG can not be recommended tbr general use outside controlled trials.

Infliximab induces apoptosis in monocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway

Background & Aims: Treatment with a chimeric anti–tumor necrosis factor (TNF) antibody (infliximab) has been shown to be highly efficient for patients with steroid-refractory Crohn's disease (CD). However, the mechanism of action remains largely unknown. As monocytopenia is commonly observed after treatment with infliximab, we investigated the role of infliximab–induced monocyte apoptosis. Methods: Peripheral blood monocytes from healthy volunteers and patients with chronic active CD (CDAI > 250) were isolated by density gradient centrifugation methods. Apoptosis was determined by annexin V staining DNA-laddering, and transmission electron microscopy. Activation of caspases and mitochondrial release of cytochrome C was determined by immunoblotting. Transcriptional activation of members of the Bcl-2 family have been analyzed by ribonuclease protection assay. Results: Treatment with infliximab at therapeutic concentrations resulted in monocyte apoptosis in patients with chronic active CD in a dose-dependent manner. Infliximab–induced monocyte-apoptosis required the activation of members of the caspase-family since activation of caspase-8, -9, and -3 could be determined. Caspase activation was induced by a CD95/CD95L independent signaling pathway with mitochondrial release of cytochrome C. Cytochrome C release seemed to be triggered by transcriptional activation of Bax and Bak. Monocyte apoptosis in vivo as determined by annexin-V binding and caspase-3 activation could be shown in patients with chronic active CD as soon as 4 hours after treatment with infliximab. Conclusions: Monocyte apoptosis induced by infliximab may be an important mechanism that could explain the powerful anti-inflammatory properties of infliximab in patients with chronic active CD.GASTROENTEROLOGY 2001;121:1145-1157

Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active crohn's disease

ISIS-2302, an antisense oligonucleotide directed against intercellular adhesion molecule 1, was effective in steroid refractory Crohn's disease in a pilot trial. The aim of this study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn's disease (CACD). A dose-interval, multicenter, placebo-controlled trial was conducted in 75 patients with steroid-refractory CACD (Crohn's Disease Activity Index [CDAI], 200-400). The primary endpoint was steroid-free remission (CDAI <150) at week 14. Only 2 of 60 (3.3%) ISIS-2302-treated and no placebo patients reached the primary endpoint. Steroid-free remission at week 26 (secondary endpoint) was reached in 8 of 60 (13.3%) active treatment and 1 of 15 (6.7%) placebo patients. A greater proportion of ISIS-2302-treated than placebo patients achieved a steroid dose <10 mg/day at weeks 14 and 26 (48.3% vs. 33.3% and 55.0% vs. 40.0%, respectively, and a glucocorticoid dose of 0 mg [prednisone equivalent] at week 26 [23.3% vs. 6.7%, respectively]). Treatment with ISIS-2302 was safe. The most common side effects were injection site reactions in the active treatment group (23% in ISIS-2302-treated patients vs. none in placebo patients). No statistically significant differences in the frequency of side effects were detected between dose groups. The trial did not prove clinical efficacy of ISIS-2302 based on the primary endpoint. Positive trends were observed in some of the secondary endpoints.

Azathioprine (AZA), methotrexate (MTX), remicade (REM) or surgery (S) in chronic active Crohn's disease (CACD) — What do patients prefer?

Azathioprine (AZA), methotrexate (MTX), remicade (REM) or surgery (S) in chronic active Crohn's disease (CACD) — What do patients prefer?

Azathioprine (AZA), methotrexate (MTX), remicade (REM) or surgery (S) in chronic active Crohn's disease (CACD) — What do patients prefer?

Azathioprine (AZA), methotrexate (MTX), remicade (REM) or surgery (S) in chronic active Crohn's disease (CACD) — What do patients prefer?

Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease

Background & Aims: Interleukin (IL)-10 is a cytokine with potent anti-inflammatory properties. We investigated the safety and efficacy of different doses of human recombinant (rhu)IL-10 in patients with Crohn's disease (CD). Methods: A prospective, multicenter, double-blind, placebo-controlled study was conducted in 329 therapy-refractory patients with CD. Clinical improvement was defined by a reduction of the Crohn's Disease Activity Index (CDAI) by 100 points or more and clinical remission by a decrease of the CDAI to <150 points. At selected centers, patients underwent ileocolonoscopies and activation of the nuclear factor–κB (NF-κB) system was assessed in biopsy specimens. Results: Subcutaneous treatment with rhuIL-10 over 28 days induced a fully reversible, dose-dependent decrease in hemoglobin and thrombocyte counts but no clinically significant side effects. No differences in the induction of remission were observed between rhuIL-10 groups (1 μg, 18% [9.6–29.2]; 4 μg, 20% [11.3–32.2]; 8 μg, 20% [11.1–31.8]; 20 μg, 28% [18–40.7]; and placebo, 18% [9.6–29.6]). Clinical improvement was observed in 46% (33.7–59) in the 8-μg/kg rhuIL-10 group in comparison with 27% (17–39.6) in patients taking placebo. Responders to rhuIL-10 showed inhibition of NF-κB p65 activation in contrast to nonresponders. Conclusions: Up to 8 μg/kg of rhuIL-10 was well tolerated. A tendency toward clinical improvement but not remission was observed in the 8-μg/kg dose group. Further studies should delineate which subgroups of patients with CD benefit from rhuIL-10 therapy.GASTROENTEROLOGY 2000;119:1461-1472

Mechanisms in failure of infliximab for Crohn's disease

Expression of tumour necrosis factor-alpha (TNF-alpha) is increased in patients with Crohn's disease. Nuclear factor kappa B (NFkappaB) controls transcription of inflammation genes. Treatment with monoclonal antibodies to TNF (infliximab) in refractory Crohn's disease results in a remission rate of 30-50% after 4 weeks. We aimed to assess the clinical and immunological mechanism of failure to respond to infliximab. 24 patients with steroid refractory, chronic active Crohn's disease (Crohn's disease activity index [CDAI]>200), who showed an inflammatory manifestation in the sigmoid colon, had a single infusion of infliximab (5 mg/kg bodyweight) and were followed up for 16 weeks. Secretion capacity for TNF-alpha was assessed in whole-blood cytokine assays and nuclear concentrations of NFkappaB p65 were determined in colonic mucosal biopsy samples. 21 (88%) of 24 patients were in remission (CDAI<150) after 1 week, ten (42%) at 4 weeks, five (21%) at 8 weeks, and two (8%) of 24 at 12 and 16 weeks. Six (29%) of 21 patients who reached remission in week 1 relapsed at week 4, 13 (62%) at week 8, 17 (81%) at week 12, and 19 (90%) at week 16. Infliximab downregulated secretion of TNF-alpha in all patients to undetectable concentrations (day 1 after infusion). Relapsers were characterised by a rise in TNF-alpha secretion capacity and by increase of mucosal nuclear NFkappaB p65 before reactivation of clinical symptoms. Infliximab greatly improved clinical symptoms in 88% of patients with Crohn's disease after 1 week. Response in some patients was of short duration. Reactivation of the mucosal and the systemic immune system preceded clinical relapse.

FDG-PET: A novel non-invasive method to detect affected bowel segments in Crohn's disease?

Crohn's disease is a chronic granulomatous disease of the gastrointestinal tract that causes discontinuous inflammation. MRI studies allow detailed analysis of affected small bowel fragments but are limited in their capacity to unequivocally determine all inflamed lesions. In the present study, we performed a prospective clinical study on the use of FDG-PET to localize affected bowel segments in patients with chronic active Crohn's disease (planned n= 50). Patients underwent endoscopy for assessment of colonic involvement, FDG-PET (370 MBq F-18 FDG and 100 MBq F-18), an examination with granulocyte antibodies (GR-AK: SPECT 4 + 24 hours poi. of 800 MBq Tc99m-GR-AK BW 250/193) and MRI analysis (HydroMRI with mannitol). A combined evaluation of MRI and PET was made by computer analysis. Among the 16 analyzed patients so far there were more positive pathologic results in FDG-PET compared to the examination with granulocyte antibodies. Furthermore, the average length of the affected bowel segments was longer in FDG-PET analysis. No case with pathologic granulocyte antibody scan but negative FDG-PET scan was noted. The ratio pathologic finding/ liver signal was on average 2,64 +/1,01 in the studies using granulocyte antibodies. The SUVmax for PET-positive lesions was on average 4,13 +/-1,03. In more than 90% of the pathologic PET findings a corresponding thickening of the small bowel wall was detected by MRI. The comparison of PET data for colonic involvement and the data obtained by endoscopic analysis showed a high correlation between PET-detected lesions and endoscopically affected areas. Taken together, these data suggest that FDG-PET analysis has a higher sensitivity to detect affected bowel wall fragments than studies with a granulocyte antibody. In contrast to MRI, PET studies also allowed the effective analysis of colonic involvement in patients with Crohn' s disease. Furthermore, FOG-PET analysis was helpful to determine the inflammatory activity in MRI-detected stenoses in Crohn's disease. Thus, FDG-PET might provide a novel reliable method for the detection and analysis of affected bowel segments in patients with chronic active Crohn's disease.