w1333 leukocyte-apheresis for steroid-refractory ulcerative colitis. results of a nationwide spanish...
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W1331
Effect of Itraconazole on Inflammatory Bowel Disease Activity in PatientsTreated for HistoplasmosisSunil Samuel, Edward V. Loftus, Karen A. Hanson, William J. Sandborn
Patients with inflammatory bowel disease (IBD) who are treated with anti-tumor necrosisfactor (TNF) agents are at increased risk for infection with Histoplasma. These patients aretreated with the anti-fungal agent itraconazole and usually have their immunosuppressivetherapy withdrawn. The azole group of anti-fungal agents (including itraconazole and clotrim-azole) has been shown to modulate the expression of various cell adhesion molecules andcytokines, resulting in a beneficial treatment effect in animal models of colitis. We soughtto assess the effect of itraconazole on IBD activity in patients treated for histoplasmosis.Methods: IBD patients who received itraconazole for histoplasmosis between 2000 and 2009were identified from a centralized institutional database. Medical records were abstractedfor clinical features and outcomes. Results: Six patients with moderate to severe inflammatorybowel disease (5 Crohn's disease, 1 ulcerative colitis) requiring treatment with anti-TNFagents ± immunosuppressives developed histoplasmosis, leading to withdrawal of anti-TNFand immunosuppressive therapy and treatment with itraconazole. The median itraconazoledose was 400mg/day (range: 200-400mg/day). Four of 6 patients (67%) had both clinicaland endoscopic evidence of disease remission after completing median treatment durationof 6 months (range: 5-12 months) with itraconazole. In these 4 patients, time to relapsewas 14, 10 and 3 months respectively in 3 patients while the 4th patient continues to remainoff all immunosuppression 3 months after stopping itraconazole (Table 1). Eighty percentof the Crohn's patients had previously developed strictures, fistulas, or abscesses, and somehad required surgical resection. While receiving itraconazole, 75% of these Crohn's patientsdiscontinued anti-TNF therapy without relapse. Conclusion: These retrospective data providepreliminary evidence that itraconazole might be effective for the treatment of inflammatorybowel disease.Table 1
* Disease flared 4 months into treatment with itraconazole. † Not available. # Histoplasmosisdiagnosis. IFX - Infliximab; AZA - azathioprine; 6-MP - 6-mercaptopurine; CD - Crohn'sdisease; UC - ulcerative colitis.
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Evaluation of the Usefulness of Azathioprine Therapy in Intestinal BehςET'sDiseaseMitsue Sogawa, Shuhei Hosomi, Masaki Takatsuka, Noriko Kamata, Hirohisa Machida,Hirotoshi Okazaki, Hirokazu Yamagami, Tetsuya Tanigawa, Kenji Watanabe, ToshioWatanabe, Kazunari Tominaga, Yasuhiro Fujiwara, Tetsuo Arakawa
Background Immunomodulaters, particularly azathioprine (AZA), are frequently used forinflammatory bowel disease, namely, Crohn's disease (CD) and ulcerative colitis (UC). Sincepatients with intestinal Behcet's (IB) disease are fewer than those with CD or UC, the medicaltreatment of the former has not been investigated extensively. The conventional steroidtherapy is used for IB disease; however, this therapy may give cause steroid resistance andsteroid dependence. Since about 2003, we have been using AZA to treat steroid-dependentpatients with IB disease at our hospital.Aim We aimed to evaluate the usefulness of AZAtherapy for IB disease at our hospital.Methods We assessed the patients to ascertain thereasons for the introduction of AZA; the dose of steroids administered at initiation and atthe assessment; the rate of endoscopically confirmed remission; the duration of remission;the duration of AZA administration; and the differences in the characteristics of AZA-responsive cases and AZA-resistant cases, all 12 cases treated with AZA, and all 30 patientswith IB disease admitted at our hospital until November, 2009.Results AZA was administeredin 9 cases (75%) for tapering the doses of steroids; in 2 cases (16.7%), for steroid dependence;and in 1 case (8.3%), for tapering of steroids after remission was achieved after the firstcourse of steroidal therapy to prevent recurrence after the operation. The dose of steroidsat the time of introducing AZA was 5~40 mg (median: 20.0 mg) and that at the assessmentwas 0~8 mg (median: 3.5 mg). When AZA was administered along with steroids, reductionof steroidal quantity was possible in all cases and discontinuation of steroids was possiblein 5 cases (41.7%). We could confirm remission by endoscopy in 9 (75%) of the 12 casestreated with AZA, and remission in these patients continued for 18~46 months (median:32 months). The duration of AZA administration was 23~83 months (median: 49 months).The differences between AZA-responsive cases and AZA-resistant cases were analyzed interms of age, sex, type of illness, incipient age, period of sickness, frequency of operation,intestinal complications, white blood cells (WBC) count, and mean corpuscular volume(MCV) and serum level of c-reactive protein (CRP). The results of this analysis showed thatAZA was more effective in women than in men (p = 0.014). Conclusion Use of AZA
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along with steroids in steroid-dependent cases with IB disease enabled dose reductionand discontinuation of steroids, with achievement of remission that could be confirmedby endoscopy.
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Leukocyte-Apheresis for Steroid-Refractory Ulcerative Colitis. Results of aNationwide Spanish RegistryJose Luis Cabriada, Nora Ibargoyen, Antonio Arin, Guillermo Bastida, Jesús Barrio,Eugeni Domènech, Joan Clofent, Daniel Ginard, Vicent Hernandez
Background: Uncontrolled studies and open series suggest that apheresis may be efficientin inducing clinical remission in steroid-refractory ulcerative colitis (UC). However, moststudies in this setting include a small number of patients. Aims: To assess the usefulness ofapheresis in steroid-refractory UC patients. Methods: All patients included in the SpanishSiMAC Registry (a nationwide Registry created to monitor the efficacy and safety of apheresisdevices for the management of UC) who were treated with apheresis in steroid-refractoryUC were identified. The Mayo Activity Index (AI) was assessed before starting apheresis,and at 1, 6, and 12 months after apheresis finished. Remission was defined as an AI≤2together with a complete steroid discontinuation, and Response as a decrease of ≥3 fromthe baseline AI. The number of apheresis sessions depended on the clinician's discretion.Results: Forty-seven patients (62% males, mean age 42y) were included. Median time fromUC diagnosis was 24.3 months, IQR [8.8-77.6]. 70% of the patients had extensive colitis,and 18 patients (38%) presented a severe flare at baseline. Cyclosporine A (CyA) had failedor induced adverse effects in 42% of patients, and 17% had failed or were intolerant toinfliximab (IFX). In 17% of cases, apheresis treatment was not complete (33% in severe UCvs 7% in mild-moderate UC, p=0,027). One month after finishing apheresis, 64% of patientspresented an initial response with 32% achieving remission; in patients with severe disease,re-mission tended to be lower than in those with mild-moderate disease (16% vs 43%, respect-ively, p=0,151).All the patients who were previously treated with IFX showed remission orresponse. A significant decrease in erythrocyte sedimentation rate (ESR) and C-reactiveprotein (CRP) levels after 3 weeks of treatment was observed in patients with initial clinicalresponse. Among patients who had an initial response, remission rate at 6 and 12 monthswas 77% and 53%, respectively. Colectomy rate at 12 months was 22%. Conclusions:Apheresis is efficient in inducing clinical remission in steroid-refractory UC, especially whenother treatments have not induced remission. However, treatment failure often occurs insevere UC, suggesting that alternative treatment algorithms should be explored in this subsetof patients (combined therapies with CyA or IFX; intensive schedules)
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Leukocyte-Apheresis for Steroid-Dependent Ulcerative Colitis. Results of aNationwide Spanish RegistryJose Luis Cabriada, Vicent Hernandez, Nora Ibargoyen, Eugeni Domènech, Joan Clofent,Daniel Ginard, Nieves Martínez-López, Oscar Roncero, Cristina Saro, Carlos Jiménez
Background: Uncontrolled studies and open series, most of them with a small number ofpatients, suggest that apheresis might be efficient in steroid-dependent ulcerative colitis(SDUC). Aims: To evaluate, in clinical practice, the usefulness of apheresis for themanagementof SDUC. Methods: All patients with SDUC included in the SiMAC Registry (a nationwideSpanish registry created by the SpanishWorking Group in IBD -GETECCU- and the Agenciesfor the Assessment of Health Technologies to monitor efficacy and safety of apheresis inUC that included a total of 195 patients) were identified. The Mayo activity index (AI) wascalculated at baseline, 1, 6 and 12 months following the last apheresis session. Remissionwas defined as a AI≤ 2 together with a complete steroid withdrawal; Response as a decreaseof ≥3 form the baseline AI; and Relapse as any flare-up that required rescue therapies(steroids, infliximab, cyclosporin or surgery). Results: 142 UC patients (62 % male, meanage 40y ±14, 61% extense colitis, median de time from UC diagnosis 42 mo -IQR: 22 to82-, 23% with previous failure or intolerance to infliximab and 85% to thiopurines). In85% apheresis was started while on systemic steroids. Initial response (one month after theinitial apheresis schedule) was 68%, with 37% of patients achieving clinical remission. Priortreatment with thiopurines/infliximab was not associated with a better/worse response. Inpatients with initial response, a significant decrease in CRP levels was observed at week 3as compared to non-responders (p=0.035). Among those patients with an initial partialresponse (response without remission), 42% achieved clinical remission at 6 months withno additional therapies. Sixty per cent and 54 % of those patients with initial response (41%and 36% of the whole series) were in clinical remission at 6 and 12 months, respectively.Conclusions: In clinical practice, 40% of SDUC patients achieve steroid-free clinical remissionat 12 months with apheresis therapy. A great proportion of those patients with an initialpartial response reach clinical remission in the mid-term. CRP levels at week 3 might bean early predictor of clinical response.
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Previous Non-Response to Infliximab Predicts Early Dose-Escalation inAdalimumab Treated Crohn's Disease PatientsEvelien Bultman, Rachel L. West, Astrid van Liere-Baron, Ernst J. Kuipers, ZuzanaZelinkova, Janneke V. Woude
INTRODUCTION: Adalimumab (ADA) is a fully human monoclonal antibody against TNF-alpha and is effective in treatment of both patients (pts) naïve and not naïve to infliximab(IFX). However, up to 60% of the pts need a dose-escalation. We aimed to determine thenumber of pts in need of dose-escalation in clinical practice. In addition, we assessed whichfactors predict the need for dose-escalation (40 mg weekly) in Crohn's disease pts treatedwith ADA. METHODS: Pts who received ADA between July 2007 and October 2009 in asingle, tertiary referral center were followed prospectively. Characteristics of pts who receivedADA for at least 3 months were assessed, including sex, age, disease duration, Montreal-classification, concomitant immunosuppressants, fistulizing disease, previous surgery for
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