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P096 - Long term results of treatment of perianal fistulas in IBD patients by advancement flap
S48 therapy (pancytopenia), but after omission the patient settled into the original condition. 28 patients of the 32 achieved remission after the second infusion of cyclophosphamide. Conclusion: Remission was maintained in all patients for 9 months on he average (mostly by CD patients) and the drug was well tolerated. Our experience suggest that intravenous pulse cyclophosphamide therapy may be a safe and effective treatment for patients with severe IBD unresponsive for conventional treatment, but further controlled study should be considered in the future in more diverse patient population. P094 Increased antigenic uptake in patients with ulcerative colitis role of CRH and muscarinic receptors C. Wallon1 , M. Persborn1 *, A.-C. Ericson1 , M. Carlson2 , P.-C. Yang3 , D.M. McKay4 , J.D. Soderholm1 . Institution of Clinical and Experimental Medicine, Link¨ oping, Sweden Background: Patients with ulcerative colitis (UC) have been shown having increased intestinal permeability. In rodent models and in healthy human volunteers, regulation of colonic uptake of antigenic sized proteins involves corticotropin releasing hormone (CRH) colinergic signalling pathways, eosinophils and mast cells. Our aim with the present study was elucidate macromolecular uptake and ion secretion in macroscopically non-inflamed colon in UC. Materials and Methods: Biopsies from fifteen UC patients in remission and fifteen healthy volunteers were assessed for macromolecular permeability (horseradish peroxidase, HRP, 51 Cr-EDTA), and electrophysiology during modulation of CRH receptors, muscarinic receptors and mast cell stabilizer. The biopsies were examined by light microscopy for CRH producing cells, eosinophils and mast cells in relation to cholinergic receptor localization. Results: There was increased permeability to HRP in UC patients (2.28±0.20 pmol/cm2 /h) compared to controls (0.99±0.19; p < 0.02). HRP permeability were normalized in UC patient samples pretreated with atropine (0.76±0.26), CRHreceptor antagonist a-helical CRH (9 41) (1.37±0.24), or the mast cell stabilizer lodoxamide tromethamine (1.16±0.28). Immunohistochemistry showed increased numbers of lamina propria eosinophils expressing muscarinic receptor subtypes M2 and M3 and CRH protein in the UC group. Conclusion: Increased transmucosal uptake of protein antigens in the non-inflamed colonic mucosa in patients with UC involves cholinergic and CRH signalling pathways, and activation of mast cells. CRH producing subepithelial eosinophils, expressing muscarinic receptors, may be involved in the regulation of this process. P095 Reducing the time to symptom improvement and resolution for moderately active UC T.R. Orchard1 *, D. Ramsey2 , S.V.D. Geest3 , S. Travis4 . 1 St. Mary’s Hospital, London, United Kingdom, 2 Procter and Gamble Pharmaceuticals, Mason, OH, USA, 3 Procter and Gamble Pharmaceuticals, Geneva, Switzerland, 4 John Radcliffe Hospital, Oxford, United Kingdom Purpose: The ECCO Consensus for the management of ulcerative colitis (UC) recommends that if rectal bleeding persists after 10 14 days, then decisive action with steroids may be necessary [1]. The purpose of this analysis was to further investigate the time to symptomatic improvement and resolution of rectal bleeding (RB), stool frequency (SF), or both RB and SF in patients with moderately active UC receiving either 4.8 g/d or 2.4 g/d mesalazine. Methods: Two randomised, double-blind, 6-week, parallelgroup studies (ASCEND I & II [2]) conducted in patients with moderately active UC were combined and analysed. Efficacy
Poster Presentations of modified-release mesalazine 4.8 g/day (800 mg tab) was compared with 2.4 g/day (400 mg tab). The median times to symptom improvement and resolution and the proportion of moderately active UC patients who experienced symptom improvement or resolution by relevant time points were calculated, based on daily diaries kept by patients through an integrated voice response system. Times to symptom improvement or resolution were defined as the number of days between the first day of dosing and the first day of symptom improvement or resolution for patients with symptoms at baseline. Symptom improvement was defined as a decrease from baseline of at least 1 point. Symptom resolution was defined as cessation of RB, normalisation of SF, or resolution of both RB and SF. Results: 687 patients with mild to moderate disease were randomised into the two studies, of which 423 analysable patients had moderately active UC. Kaplan Meier results for time to symptom improvement and resolution for 2.4 g/day and 4.8 g/day are shown below. Median time to symptom improvement of both RB and SF was 7 days for 4.8 g/day vs 9 days for 2.4 g/day (p = 0.02). At day 7, 52% of patients receiving 4.8 g/day achieved symptomatic improvement in both RB and SF compared to 43% receiving 2.4 g/day. At day 14, more patients achieved symptomatic improvement for both RB and SF on 4.8 g/day compared to 2.4 g/day (73% vs 61%). Median time to symptom resolution of both RB and SF was 19 days for 4.8 g/day vs 29 days for 2. 4 g/day (p = 0.02). By day 14, resolution of rectal bleeding was achieved in 64% vs 49%, normalisation of stool frequency in 58% vs 50% and of both RB and SF in 43% vs 30% for 4.8 g/day and 2.4 g/d, respectively. Conclusion: Mesalazine 4.8 g/day for patients with moderately active UC results in faster symptom improvement and resolution than 2.4 g/day. 14 days is a nodal point for deciding whether to escalate therapy; prescribing mesalazine 4.8 g/day from the start of a flare could avoid the need for steroids in some patients.
Time to resolution/improvement of both rectal bleeding and stool frequency. Combined data for ASCEND I&II moderate patients. Reference(s) [1] Travis SPL et al. Journal of Crohn’s and Colitis (2008) 2, 24 62. [2] Hanauer et al. Am J Gastroenterol 2005;100:2478 2485. P096 Long term results of treatment of perianal fistulas in IBD patients by advancement flap Z. Serclova *, F. Antos Sr.. University Hospital Bulovka, Prague 8, Czech Republic Introduction: Perianal fistulization significantly influences life quality of patients suffering from IBD. This form of disease is
Abstracts of the 4th Congress of ECCO
the European Crohn’s and Colitis Organisation
the centre of attention of studies which deal with biological therapy because reducing secretion from fistulas and reducing of symptoms are the criteria of therapy’s success. However, fistulas’ tracts remain even after this treatment. We consider as rational to combine biological therapy (reduction of inflammatory response) and surgical eradication of fistulas using excision and advancement flap (AF) method. Aim of study: In our study we retrospectively assess the long term results of combined therapy of perianal fistulas (medicament and surgical) at our department in patients with IBD (1/2002 4/2008) using AF method. Patients and Methods: We treated 37 patients with this method in course of above stated period. After general examination and examination of the proximal intestinal disease we examined all patients under general anesthesia including drainage and discission of secondary tracts; in portion of patients repeated discisions and re-drainages according to finding was needed and after fibrotization and simplification of tracts we performed advancement flap method. Concomitant antibiotic, immunosuppressive and biological therapy was administrated. The sample contained 21 females (average age 37 years) and 16 males (average age 36 years). All patients suffered from complex perianal fistulas; 9 females (42%) suffered from vaginal fistula, 3 of them had additional perianal fistula. Prior to eradication of fistula we had to perform 2.11 drainages or discissions on average in course of 7.6 months (median) including medicamentous therapy. Definitive healing occurred in 78% (28 patients) during the follow-up of 5 72 months (median was 19 months; mean was 29 months). 6 patients from the total number had to underwent more than one AF; definitive healing did not occur in only 2 patients of them. We did not reach the eradication of fistulas in 7 patients (19%), 1 of those patients has permanent ileostomy and another 2 patients from the healed group have permanent stomy due to intestinal reasons. 1 patient died in a car accident. Conclusion: Combination of conservative treatment with rational surgical therapy is very successful in treatment of perianal fistulization and patients profit from this method even according to relatively long follow-up period (78% patient healed completely with the average follow-up of 29 months and with median of 19 months) which present much longer efficacy than it is known in case of biological therapy alone. Combination of both methods increases probably the efficacy of surgical therapy. P097 What factors influence adhesion to therapy in inflammatory bowel disease? F. Bermejo1 *, A. L´ opez-Sanrom´ an2 , A. Algaba1 , J.A. Carneros1 , 1 1 M. Valer , S. S´ anchez , B. Piqueras1 , S. García1 , I. Guerra1 , F. García1 , E. Tom´ as1 , J.L. Rodríguez1 . 1 Fuenlabrada University Hospital, Fuenlabrada, Spain, 2 Ram´ on y Cajal University Hospital, Madrid, Spain Aims: Inflammatory bowel disease (IBD) is a clinical condition associated with a high risk of deficient adhesion to therapy. Our aim was to analyze the degree of adhesion to treatment in a specialized IBD Clinic, and to study which factors could influence it. Methods: A total of 107 consecutive patients were included during a three-month period. With previous consent and in all privacy, patients filled up an anonymous survey with demographic data (age, gender, study level, working status, personal status), data concerning the disease (type of IBD, year of diagnosis, number of hospital admissions, IBD-related surgical procedures), data about therapy (drug, dose, interval), self-applied adhesion declaration (Sewitch MJ et al. Am J Gastroenterol 2003) and self-medication. An activity index was calculated on the spot (Harvey Bradshaw/Truelove).
S49
Results: Mean age was 41.3±11 years, 60% were women, the number of years since IBD diagnosis was 7.9±7. The diagnosis was Crohn’s in 64% (71% inactive), ulcerative colitis 36% (70% inactive). A 66% was treated with aminosalicylates, a 51% with immunosuppressors, 8% with glucocorticoids. A 66% needed an IBD-related hospital admission in the past, and 17% any IBDrelated surgical procedure. A 69% (95% CI: 60 77%) showed some type of non-adhesion. A 66% (95% CI: 57 75%) acknowledged dome degree of involuntary non-adhesion: either forgetting to take their dose (63%) or being careless about having taken it (27%). A 16% (95% CI: 9 22%) showed some kind of voluntary non-adhesion: interrupting the therapy when feeling better (13%) or when feeling worse (6%). A 25% (95% CI: 17 33%) forgot at least a dose a week (mean weekly number of forgotten doses 1.6), and the most frequent cause was to be away form home when they were supposed to take the medication. This was more frequent under mesalazine therapy (30%) than with azathioprine (17%) (p=n.s.). A multivariate analysis identified as risk factors for a lower adhesion the dosing in three or more takes a day (OR 3; 95% CI 1.1 8.4; p = 0.03) and feeling little informed about their disease (OR 4.9; 95% CI 1.1 23.8; p = 0.04). On the other hand, immunomodulator therapy was a predictive factor for better adhesion (OR 0.29; 95% CI 0.11 0.74; p = 0.01). The concordance between patient recall and clinical records was complete in 86%, whereas in 10.3% the patients did not accurately remember the dose and in 3.7% there was confusion about the drug taken. A 9% acknowledged self-medication during flares. Conclusions: In our setting, adhesion to therapy in IBD patients is not satisfactory. Patients treated with immunosuppressors have better adhesion. Optimizing the information on the disease and giving the medication in one or two daily doses could enhance therapeutic adhesion. P098 Optimizing treatment of perianal fistulae in Crohn’s disease results from an interdisciplinary approach U. Strauch *, F. Obermeier, H. Schlitt, J. Sch¨ olmerich, I. Iesalnieks. University Clinic of Regensburg, Regensburg, Germany Aim: Perianal fistulae are common in individuals with Crohn’s disease (CD) and occur in approximately 1/3 of all CD patients. Aim of our study was to optimize treatment by a standardized interdisciplinary approach. Materials and Methods: All patients with CD and perianal fistulae were seen together by a specialized surgeon and gastroenterologist. Treatment (medical and surgical) of symptomatic fistulae was planed based upon the type of fistulae that were classified according to Park’s classification in subcutaneous, deep and high intersphincteric, deep and high transsphincteric, suprasphincteric, and extrasphincteric as well as rectovaginal fistulae. Primary treatment for symptomatic deep fistulae was fistulotomy without specific medical therapy. In high transsphincteric fistulae a seton was placed and immunsuppressive therapy with azathioprine was initiated. If efficacy was missing or the drug was not tolerated, antiTNF-treatment was started. Treatment result was called “optimal” if patient was not in need for a stoma, if healing of fistulae was observed after fistulotomy and if symptoms after seton-placement were controlled adequately without need for change of therapy or further surgery. Results: 139 patients with CD and perianal fistulae were admitted to the interdisciplinary ward. 66 of these patients had to undergo surgery. 52% of all patients were asymptomatic despite the presence of fistulae, were treated sufficiently with antibiotics or already received immunosuppressants with good control of fistula symptoms. 10.6% of patients undergoing surgery were in need for abdominoperineal extirpation of the rectum and 4.5% received a temporary stoma. 64% of patients
Poster Presentations of modified-release mesalazine 4.8 g/day (800 mg tab) was compared with 2.4 g/day (400 mg tab). The median times to symptom improvement and resolution and the proportion of moderately active UC patients who experienced symptom improvement or resolution by relevant time points were calculated, based on daily diaries kept by patients through an integrated voice response system. Times to symptom improvement or resolution were defined as the number of days between the first day of dosing and the first day of symptom improvement or resolution for patients with symptoms at baseline. Symptom improvement was defined as a decrease from baseline of at least 1 point. Symptom resolution was defined as cessation of RB, normalisation of SF, or resolution of both RB and SF. Results: 687 patients with mild to moderate disease were randomised into the two studies, of which 423 analysable patients had moderately active UC. Kaplan Meier results for time to symptom improvement and resolution for 2.4 g/day and 4.8 g/day are shown below. Median time to symptom improvement of both RB and SF was 7 days for 4.8 g/day vs 9 days for 2.4 g/day (p = 0.02). At day 7, 52% of patients receiving 4.8 g/day achieved symptomatic improvement in both RB and SF compared to 43% receiving 2.4 g/day. At day 14, more patients achieved symptomatic improvement for both RB and SF on 4.8 g/day compared to 2.4 g/day (73% vs 61%). Median time to symptom resolution of both RB and SF was 19 days for 4.8 g/day vs 29 days for 2. 4 g/day (p = 0.02). By day 14, resolution of rectal bleeding was achieved in 64% vs 49%, normalisation of stool frequency in 58% vs 50% and of both RB and SF in 43% vs 30% for 4.8 g/day and 2.4 g/d, respectively. Conclusion: Mesalazine 4.8 g/day for patients with moderately active UC results in faster symptom improvement and resolution than 2.4 g/day. 14 days is a nodal point for deciding whether to escalate therapy; prescribing mesalazine 4.8 g/day from the start of a flare could avoid the need for steroids in some patients.
Time to resolution/improvement of both rectal bleeding and stool frequency. Combined data for ASCEND I&II moderate patients. Reference(s) [1] Travis SPL et al. Journal of Crohn’s and Colitis (2008) 2, 24 62. [2] Hanauer et al. Am J Gastroenterol 2005;100:2478 2485. P096 Long term results of treatment of perianal fistulas in IBD patients by advancement flap Z. Serclova *, F. Antos Sr.. University Hospital Bulovka, Prague 8, Czech Republic Introduction: Perianal fistulization significantly influences life quality of patients suffering from IBD. This form of disease is
Abstracts of the 4th Congress of ECCO
the European Crohn’s and Colitis Organisation
the centre of attention of studies which deal with biological therapy because reducing secretion from fistulas and reducing of symptoms are the criteria of therapy’s success. However, fistulas’ tracts remain even after this treatment. We consider as rational to combine biological therapy (reduction of inflammatory response) and surgical eradication of fistulas using excision and advancement flap (AF) method. Aim of study: In our study we retrospectively assess the long term results of combined therapy of perianal fistulas (medicament and surgical) at our department in patients with IBD (1/2002 4/2008) using AF method. Patients and Methods: We treated 37 patients with this method in course of above stated period. After general examination and examination of the proximal intestinal disease we examined all patients under general anesthesia including drainage and discission of secondary tracts; in portion of patients repeated discisions and re-drainages according to finding was needed and after fibrotization and simplification of tracts we performed advancement flap method. Concomitant antibiotic, immunosuppressive and biological therapy was administrated. The sample contained 21 females (average age 37 years) and 16 males (average age 36 years). All patients suffered from complex perianal fistulas; 9 females (42%) suffered from vaginal fistula, 3 of them had additional perianal fistula. Prior to eradication of fistula we had to perform 2.11 drainages or discissions on average in course of 7.6 months (median) including medicamentous therapy. Definitive healing occurred in 78% (28 patients) during the follow-up of 5 72 months (median was 19 months; mean was 29 months). 6 patients from the total number had to underwent more than one AF; definitive healing did not occur in only 2 patients of them. We did not reach the eradication of fistulas in 7 patients (19%), 1 of those patients has permanent ileostomy and another 2 patients from the healed group have permanent stomy due to intestinal reasons. 1 patient died in a car accident. Conclusion: Combination of conservative treatment with rational surgical therapy is very successful in treatment of perianal fistulization and patients profit from this method even according to relatively long follow-up period (78% patient healed completely with the average follow-up of 29 months and with median of 19 months) which present much longer efficacy than it is known in case of biological therapy alone. Combination of both methods increases probably the efficacy of surgical therapy. P097 What factors influence adhesion to therapy in inflammatory bowel disease? F. Bermejo1 *, A. L´ opez-Sanrom´ an2 , A. Algaba1 , J.A. Carneros1 , 1 1 M. Valer , S. S´ anchez , B. Piqueras1 , S. García1 , I. Guerra1 , F. García1 , E. Tom´ as1 , J.L. Rodríguez1 . 1 Fuenlabrada University Hospital, Fuenlabrada, Spain, 2 Ram´ on y Cajal University Hospital, Madrid, Spain Aims: Inflammatory bowel disease (IBD) is a clinical condition associated with a high risk of deficient adhesion to therapy. Our aim was to analyze the degree of adhesion to treatment in a specialized IBD Clinic, and to study which factors could influence it. Methods: A total of 107 consecutive patients were included during a three-month period. With previous consent and in all privacy, patients filled up an anonymous survey with demographic data (age, gender, study level, working status, personal status), data concerning the disease (type of IBD, year of diagnosis, number of hospital admissions, IBD-related surgical procedures), data about therapy (drug, dose, interval), self-applied adhesion declaration (Sewitch MJ et al. Am J Gastroenterol 2003) and self-medication. An activity index was calculated on the spot (Harvey Bradshaw/Truelove).
S49
Results: Mean age was 41.3±11 years, 60% were women, the number of years since IBD diagnosis was 7.9±7. The diagnosis was Crohn’s in 64% (71% inactive), ulcerative colitis 36% (70% inactive). A 66% was treated with aminosalicylates, a 51% with immunosuppressors, 8% with glucocorticoids. A 66% needed an IBD-related hospital admission in the past, and 17% any IBDrelated surgical procedure. A 69% (95% CI: 60 77%) showed some type of non-adhesion. A 66% (95% CI: 57 75%) acknowledged dome degree of involuntary non-adhesion: either forgetting to take their dose (63%) or being careless about having taken it (27%). A 16% (95% CI: 9 22%) showed some kind of voluntary non-adhesion: interrupting the therapy when feeling better (13%) or when feeling worse (6%). A 25% (95% CI: 17 33%) forgot at least a dose a week (mean weekly number of forgotten doses 1.6), and the most frequent cause was to be away form home when they were supposed to take the medication. This was more frequent under mesalazine therapy (30%) than with azathioprine (17%) (p=n.s.). A multivariate analysis identified as risk factors for a lower adhesion the dosing in three or more takes a day (OR 3; 95% CI 1.1 8.4; p = 0.03) and feeling little informed about their disease (OR 4.9; 95% CI 1.1 23.8; p = 0.04). On the other hand, immunomodulator therapy was a predictive factor for better adhesion (OR 0.29; 95% CI 0.11 0.74; p = 0.01). The concordance between patient recall and clinical records was complete in 86%, whereas in 10.3% the patients did not accurately remember the dose and in 3.7% there was confusion about the drug taken. A 9% acknowledged self-medication during flares. Conclusions: In our setting, adhesion to therapy in IBD patients is not satisfactory. Patients treated with immunosuppressors have better adhesion. Optimizing the information on the disease and giving the medication in one or two daily doses could enhance therapeutic adhesion. P098 Optimizing treatment of perianal fistulae in Crohn’s disease results from an interdisciplinary approach U. Strauch *, F. Obermeier, H. Schlitt, J. Sch¨ olmerich, I. Iesalnieks. University Clinic of Regensburg, Regensburg, Germany Aim: Perianal fistulae are common in individuals with Crohn’s disease (CD) and occur in approximately 1/3 of all CD patients. Aim of our study was to optimize treatment by a standardized interdisciplinary approach. Materials and Methods: All patients with CD and perianal fistulae were seen together by a specialized surgeon and gastroenterologist. Treatment (medical and surgical) of symptomatic fistulae was planed based upon the type of fistulae that were classified according to Park’s classification in subcutaneous, deep and high intersphincteric, deep and high transsphincteric, suprasphincteric, and extrasphincteric as well as rectovaginal fistulae. Primary treatment for symptomatic deep fistulae was fistulotomy without specific medical therapy. In high transsphincteric fistulae a seton was placed and immunsuppressive therapy with azathioprine was initiated. If efficacy was missing or the drug was not tolerated, antiTNF-treatment was started. Treatment result was called “optimal” if patient was not in need for a stoma, if healing of fistulae was observed after fistulotomy and if symptoms after seton-placement were controlled adequately without need for change of therapy or further surgery. Results: 139 patients with CD and perianal fistulae were admitted to the interdisciplinary ward. 66 of these patients had to undergo surgery. 52% of all patients were asymptomatic despite the presence of fistulae, were treated sufficiently with antibiotics or already received immunosuppressants with good control of fistula symptoms. 10.6% of patients undergoing surgery were in need for abdominoperineal extirpation of the rectum and 4.5% received a temporary stoma. 64% of patients