Crohn Disease: Domènech E

Domènech E, Esteve M, Gomollón F, Hinojosa J, Panés J, Obrador A, Gassull MA, Anonymous00132. · Servicio de Aparato Digestivo, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain. · Gastroenterol Hepatol. · Pubmed #15771858 No free full text.

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Domènech E, Esteve-Comas M, Gomollón F, Hinojosa J, Obrador A, Panés J, Gassull MA, Anonymous00043. · Hospital Universitari Germans Trías i Pujol, Badalona, Barcelona, Spain. · Gastroenterol Hepatol. · Pubmed #11864540 No free full text.

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Domènech E, Hinojosa J, Nos P, Garcia-Planella E, Cabré E, Bernal I, Gassull MA. · Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain. · Aliment Pharmacol Ther. · Pubmed #16305724 links to  free full text

Abstract: BACKGROUND: Few data are available regarding the evolution of Crohn's disease after discontinuing a successful course of infliximab. AIM: To evaluate clinical outcome of Crohn's disease after induction of remission with three infliximab infusions (luminal disease) and after maintenance of remission with 1-year course of infliximab every 8 weeks (luminal and perianal). METHODS: Twenty-three patients with active luminal Crohn's disease who responded to three infusions of infliximab (0, 2, and 6 weeks), and 23 patients with sustained response to infliximab every 8 weeks during 1 year, were included. Patients were followed-up until relapse or for at least 6 months after infliximab discontinuation. Clinical outcomes and factors associated to relapse were evaluated. RESULTS: In luminal Crohn's disease, a three-infusion infliximab regimen achieved a sustained response in most patients, especially if a complete response occurred at the time of the third infusion. In patients treated for 1-year, infliximab discontinuation was also successful, with a cumulative probability of being free of relapse of 69% at 12 months. In perianal disease, early relapse was the rule after stopping infliximab treatment, with only 34% of patient maintaining remission at 1 year. CONCLUSIONS: Short regimens of infliximab might be evaluated in patients with luminal Crohn's disease. However, infliximab discontinuation is not recommended in perianal Crohn's disease, because of a high rate of early relapse.

Domènech E, Mañosa M, Navarro M, Masnou H, Garcia-Planella E, Zabana Y, Cabré E, Gassull MA. · Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s/n, Badalona, Catalonia, Spain. · J Clin Gastroenterol. · Pubmed #18277899 No free full text.

Abstract: GOALS: To assess the efficacy and safety profile of methotrexate (MTX) for the treatment of Crohn's disease (CD) in clinical practice. BACKGROUND: MTX is widely used for some chronic immunologic diseases. Although some randomized controlled trials suggest its efficacy in CD, this drug remains a second-line, underused, immunomodulator. STUDY: Medical records of all patients treated with MTX for CD in our center (n=44) were reviewed. Clinical and epidemiologic parameters, including risk factors for hepatotoxicity, were registered. RESULTS: MTX was prescribed mainly for steroid-dependency (n=22) and as concomitant treatment to infliximab (n=18). Mean duration of treatment was 22.9+/-19 months, with a mean cumulative dose of MTX of 1169+/-784 mg. Thirty-nine percent of patients developed drug-related side effects, hepatotoxicity being the most frequent [13 patients (30%)]. However, only 5 patients (11%) had to discontinue MTX. In steroid-dependent CD patients, disease remission and complete steroid withdrawal was achieved in 77% of cases. Seven patients lost their initial response to MTX during follow-up, leading to a cumulative probability of remission of 39% after 3 years of treatment. CONCLUSIONS: MTX is well tolerated in most CD patients. Although a great proportion of steroid-dependent CD patients achieve disease remission and steroid withdrawal, there is a trend to a loss of efficacy with time. Larger, long-term studies are necessary to establish the role of MTX in the management of CD.

Domènech E, Mañosa M, Bernal I, Garcia-Planella E, Cabré E, Piñol M, Lorenzo-Zúñiga V, Boix J, Gassull MA. · Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain. · Inflamm Bowel Dis. · Pubmed #18183602 links to  free full text

Abstract: BACKGROUND: Postoperative recurrence (PR) occurs early after intestinal resection in >75% of Crohn's disease (CD) patients. No well-established strategy for long-term PR prevention is available. The aim was to prospectively evaluate the long-term endoscopic and clinical outcomes of postoperative CD on maintenance treatment with azathioprine (AZA), especially in patients who developed endoscopic lesions confined to the ileocolic anastomosis. METHODS: Long-term AZA therapy (2-2.5 mg/kg/day) was initiated immediately after surgery in 56 consecutive patients who underwent a curative intestinal resection. Clinical and biological assessments every 3 months, as well as yearly endoscopic evaluation, were performed until the end of the study or clinical PR (CPR). RESULTS: Thirty-seven patients (70%) showed mucosal lesions at endoscopy after a median of 12 months (range 12-60); however, in 15 of these patients lesions were confined to the anastomosis and only 6 showed endoscopic progression, but none of them developed CPR. Among the remaining 22 patients with endoscopic PR (EPR), 23% suffered a CPR during follow-up. Thirty percent of patients remained free of EPR after a median follow-up of 33 months (range 12-84). The cumulative probability of EPR was 44%, 53%, 69%, and 82%, at 1, 2, 3, and 5 years, respectively. No predictive factors of EPR were found. CONCLUSIONS: Early postoperative use of AZA seems to delay EPR development in comparison to historical series or placebo groups in randomized controlled trials. Although usually considered as endoscopic recurrence, those lesions confined to the ileocolonic anastomosis are not likely to progress or to become symptomatic in the short term.

Domènech E, Garcia-Planella E, Olazábal A, Sánchez-Delgado J, Zabana Y, Bernal I, Mañosa M, Olivé A, Gassull MA. · Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain. · Dig Dis Sci. · Pubmed #15986866 No free full text.

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Domènech E, Nos P, Papo M, López-San Román A, Garcia-Planella E, Gassull MA. · Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. · Scand J Gastroenterol. · Pubmed #15841714 No free full text.

Abstract: OBJECTIVE: Azathioprine and 6-mercaptopurine are useful therapies in inflammatory bowel diseases. Despite their efficacy, their use is limited owing to treatment intolerance or toxicity in 10-15% of patients. It has been suggested that both drugs could be interchangeable. MATERIAL AND METHODS: All patients treated with 6-mercaptopurine because of previous digestive intolerance of azathioprine in four Spanish hospitals were reviewed. Tolerance of 6-mercaptopurine therapy was assessed. RESULTS: Fifteen patients (11 Crohn's disease, 4 ulcerative colitis) were included. Immunosuppressant therapy was prescribed for steroid-dependent disease in 13 cases, and for perianal disease in 2. Main symptoms of digestive intolerance were epigastric pain, nausea and vomiting, which developed within the first weeks of treatment. Acute pancreatitis was ruled out in all the cases. Five patients commenced 6-mercaptopurine immediately after azathioprine discontinuation and 7 patients within the first month. Eleven patients (73.3%) tolerated 6-mercaptopurine and reached the therapeutic goals; only two patients had to discontinue 6-mercaptopurine because of adverse effects. CONCLUSIONS: Treatment with 6-mercaptopurine is a safe alternative in patients with inflammatory bowel diseases and previous digestive intolerance of azathioprine.

Domènech E, Hinojosa J, Esteve-Comas M, Gomollón F, Herrera JM, Bastida G, Obrador A, Ruiz R, Saro C, Gassull MA, Anonymous00177. · Hospital Universitari Germans Trias i Pujol, Badalona, Spain. · Aliment Pharmacol Ther. · Pubmed #15606397 links to  free full text

Abstract: BACKGROUND: Uncontrolled studies suggest that granulocyteaphaeresis might be useful in the management of active ulcerative colitis. AIM: To assess the efficacy of granulocyteaphaeresis treatment in active steroid-dependent inflammatory bowel disease. METHODS: We conducted a multicentre, prospective, open, pilot study in patients with steroid-dependent inflammatory bowel disease. All patients were started on 60 mg/day of prednisone; after 1 week, a five-session programme of granulocyteaphaeresis (once per week) was started. The steroid dose was tapered weekly if there was clinical improvement. Remission was defined as an inactive clinical activity index together with complete withdrawal of steroids at week 6. The patients were followed up for at least 6 months or until disease relapse. RESULTS: Twenty-six patients (14 ulcerative colitis, 12 Crohn's disease) were included. More than a half had been previously treated with immunomodulators. Remission was achieved in 62 and 70% of ulcerative colitis and Crohn's disease, respectively. During a median follow-up of 12.6 months, six of eight ulcerative colitis patients maintained their clinical remission; however, only one Crohn's disease patient remained in remission after the first 6 months of follow-up. CONCLUSIONS: Granulocyteaphaeresis is a safe treatment option in inflammatory bowel disease. A five-session programme of granulocyteaphaeresis seems to be efficient in the treatment of steroid-dependent ulcerative colitis, but not in Crohn's disease.

Domènech E, Scala L, Bernal I, García-Planella E, Casalots A, Piñol M, Esteve-Comas M, Cabré E, Boix J, Gassull MA. · Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. · Gastroenterol Hepatol. · Pubmed #15574279 No free full text.

Abstract: OBJECTIVES: Surgical resection is still a mainstay of the treatment of Crohn's disease (CD). However, recurrence is the rule. The aim of the present study was to evaluate CD recurrence in a series of patients who underwent surgical resection with subsequent treatment with azathioprine (AZA) or mesalazine (5-ASA) and to identify the factors associated with recurrence. METHODS: The medical records of patients with CD who underwent bowel resection during a 4-year period were reviewed. Only patients who received AZA or 5-ASA as prophylaxis for recurrence were included. RESULTS: Thirty-three patients treated with AZA and 16 treated with 5-ASA were included. Endoscopic recurrence was found in 8.6% of the AZA group and in 87.5% of the 5-ASA group (p <0.001). Clinical recurrence occurred in 31.2% of patients in the 5-ASA group and in none in the AZA group (p=0.004). The accumulated probability of both clinical and endoscopic recurrence was significantly lower in the AZA group (p=0.0025 and p=0.005, respectively). Factors associated with a greater risk of endoscopic recurrence were termino-terminal anastomosis and 5-ASA treatment. The only factor associated with clinical recurrence was 5-ASA treatment. CONCLUSION: AZA seems to be more effective than 5-ASA in the prevention of postsurgical endoscopic recurrence of CD. Prospective studies with long-term follow-up are required to establish the true utility of AZA in the prophylaxis of CD recurrence.

Garcia-Planella E, Domènech E, Esteve-Comas M, Bernal I, Cabré E, Boix J, Gassull MA. · Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain. · Eur J Gastroenterol Hepatol. · Pubmed #12655253 No free full text.

Abstract: BACKGROUND: Although the efficacy of infliximab in Crohn's disease (CD) has been demonstrated, its safety profile has yet to be established. Autoimmune adverse events such as human anti-chimeric antibodies and the development of antinuclear antibodies (ANAs) have been notified, but the true incidence and clinical relevance of the latter is still unknown. OBJECTIVE: To evaluate the changes in ANA status in CD patients treated with infliximab and the clinical evolution of those who are ANA positive. METHODS: The ANA status of 36 CD patients treated with infliximab was determined at baseline and 6 weeks after the initial infliximab infusion. Patients were followed up monthly. In the case of infliximab re-treatment, ANA status was again evaluated. Twenty-eight patients (78%) were treated concomitantly with immunosuppressants. RESULTS: Eight patients (22%) were ANA positive at baseline; none developed anti-double-stranded DNA antibodies (aDNAds) at week 6. Three of them were re-treated: there were increasing ANA titres in all cases and developing aDNAds in two. Only six of 28 patients who were ANA negative at baseline changed their ANA status at week 6, but none developed aDNAds. One of them was retreated showing a further increase in ANA titre and developing aDNAds at high titre. No patient presented lupus-like syndrome. CONCLUSIONS: Only a few CD patients treated with infliximab and immunosuppressants develop ANAs. This condition is not associated with aDNAds and/or lupus-like syndrome in the majority of cases.

Bernal I, Domènech E, García-Planella E, Cabré E, Gassull MA. · Servicio de Aparato Digestivo. Hospital Universitari Germans Trias i Pujol. Badalona. Barcelona. España. · Gastroenterol Hepatol. · Pubmed #12525323 No free full text.

Abstract: Immunosuppressive agents (azathioprine, methotrexate) are increasingly being used in the treatment of inflammatory bowel disease. The use of immunosuppressive agents is associated with a greater risk of opportunistic infections, the most frequent of which are those caused by cytomegalovirus and varicella zoster virus.We present four cases of opportunistic infections due to Herpesviruses in patients undergoing immunosuppressive treatment with azathioprine for Crohn's disease. We also review the literature published on this topic.Two patients presented cutaneous varicella complicated by pneumonia and esophagitis respectively, one patient had cutaneous herpes zoster and the other had fatal pneumonia possibly caused by the Herpesvirus. In the first three the clinical course of the infection was favorable after withdrawing immunosuppressant treatment and initiating treatment with aziclovir.In patients Crohn's disease azathioprine treatment increases the risk of opportunistic infection by Herpesvirus. However, in the absence of other factors that increase immunosuppression, these infections usually have a benign course with specific antiviral therapy.

García-Planella E, Domènech E, Cabré E, Bernal MI, Gassull MA. · Servicio de Aparato Digestivo. Hospital Universitari Germans Trias i Pujol. Badalona. Barcelona. España. · Med Clin (Barc). · Pubmed #12433336 No free full text.

Abstract: BACKGROUND: Intravenous cyclosporine (iv CyA) is efficient in ulcerative colitis, but data are scarce in Crohn's disease (CD). PATIENTS AND METHOD: Patients with CD refractory to standard therapy who were treated with iv CyA. RESULTS: All patients with steroid-refractory disease achieved a complete response. In perianal disease, a complete response was attained in 3 out of 16 patients, while 9 showed a partial response. Only 1 out of 8 patients with enteric fistulae showed a complete response and a further one had a partial response. CONCLUSIONS: Intravenous CyA seems to be useful in steroid-refractory CD but not in fistulizing CD.

Vega R, Bertrán X, Menacho M, Domènech E, Moreno de Vega V, Hombrados M, Cabré E, Ojanguren I, Gassull MA. · Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain. · Am J Gastroenterol. · Pubmed #10201482 No free full text.

Abstract: OBJECTIVE: It has been suggested that, in inflammatory bowel disease, cytomegalovirus behaves in the intestine as a nonpathogenic bystander, and even its finding in intestinal mucosa has unclear clinical relevance. We report our experience with a small series of patients with refractory inflammatory bowel disease and cytomegalovirus infection and their clinical outcome. METHODS AND RESULTS: Nine patients with moderate-severe attacks of inflammatory bowel disease did not respond to i.v. prednisone (1 mg/kg/day) for a mean of 24 days. Four of these patients were further treated with i.v. cyclosporine A (4 mg/kg/day). Cytomegalovirus infection was diagnosed in two patients after resection for treatment failure. In the remaining patients, cytomegalovirus infection was diagnosed in endoscopic mucosal biopsies and i.v. ganciclovir was then administered at a dose of 10 mg/kg/day for 2-3 wk. Five of these patients went into clinical remission, allowing corticosteroid and cyclosporine A discontinuation. Follow-up biopsies were performed and in all cases cytomegalovirus could not be detected in the colonic tissue. Two patients needed to be treated with intravenous cyclosporine A after antiviral therapy because of persistence of clinical symptoms despite the elimination of cytomegalovirus infection. CONCLUSIONS: Cytomegalovirus infection may play a role in the natural history of refractory inflammatory bowel disease and in some of its complications. The clearance of cytomegalovirus in colonic mucosa may lead some of these patients to remission.

Mañosa M, Domènech E, Marín L, Olivé A, Zabana Y, Cabré E, Gassull MA. · No affiliation provided · Gut. · Pubmed #18334664 No free full text.

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Domènech E, Mañosa M, Masnou H, Navarro M, Garcia-Planella E, Bernal I, Gassull MA. · No affiliation provided · Am J Gastroenterol. · Pubmed #15667513 No free full text.

This publication has no abstract.