- Email: [email protected]
P027 TREATMENT OF PERIANAL CROHN'S DISEASE WITH COMBINED SURGICAL AND BIOLOGICAL THERAPY
Abstracts of the 3rd ECCO Congress, Lyon, France, February 28–March 1, 2008
13
P025 MAINTENANCE Q8 THERAPY OF CROHN' S DISEASE WITH INFLIXIMAB IS ASSOCIATED WITH ENDOSCOPIC MUCOSAL HEALING IN THE LONG-TERM
TNF antibodies compared to placebo. These results must be confirmed in patients treated in clinical practice and with a longer follow-up.
F. Schnitzler, H. Fidder, M. Ferrante, M. Noman, G. Van Assche, I. Hoffman, S. Vermeire, P. Rutgeerts. University Hospital Leuven, Leuven, Belgium
P027 TREATMENT OF PERIANAL CROHN' S DISEASE WITH COMBINED SURGICAL AND BIOLOGICAL THERAPY
Introduction: The ACCENT I endoscopy substudy could demonstrate that maintenance therapy of Crohn' s disease (CD) with infliximab (IFX) q8 weeks is associated with mucosal healing over a 1 year period, leading to considerably fewer hospitalisations and surgeries. No data exist on the endoscopic outcome of IFX for CD long-term in clinical practice. Aims and methods: We studied mucosal healing during long-term treatment with IFX in a consecutive series of 614 CD patients, treated with IFX between 1995 and November 2007, by analyzing the reports from endoscopy performed during IFX treatment. Complete healing was defined as absence of ulcerations and partial healing as clear endoscopic improvement but still signs of inflammation. No healing was concluded in case of no endoscopic improvement. Results: During a median follow-up of 59 months (IQR 32-85), 8091 IFX infusions were administered. A total of 547 patients (89%) showed short term response whereas in 67 patients (10.9%) IFX had to be stopped for lack of response. In 388 patients, endoscopy was performed within a median of 1.61 months (IQR 0.16-8.91) prior to first IFX and 263 patients with initial response and further retreatment underwent endoscopy (1st endoscopy after start of IFX taken) after a median of 11.05 months (IQR 2.17-28.19) after start of IFX. IFX treatment in these patients was scheduled in 33.5%, episodic in 24.7% and episodic with switch to maintenance in 41.8%. More than two thirds (64.1%) were under concomitant immunomodulators (IM) and 35 patients received corticosteroids (CS). Overall, 61.2% of the 263 initial responders (n=161) showed mucosal healing, with 106 patients having full mucosal healing (40.3%) and 55 (20.9%) partial healing after a median of 4 IFX infusions (IQR 2-11). Patients with scheduled treatment from the start were more likely to show mucosal healing than patients who were started on episodic treatment (67/88 versus 94/175 respectively, p<0.0001, Odds ratio 2.75 (95%CI 1.55 - 4.88)). Concomitant IM had no influence on the healing rates (60.1% with IM vs. 59.8% without IM, p=0.96), whereas patients under CS had lower healing rates (15/35, 42.9%) than patients without CS (147/235, 62.6%, p=0.026). Of the patients showing sustained clinical benefit till end of FU (112/170), 65.9% had mucosal healing compared to 50% of patients (50/100) who had to stop IFX for loss of response or side effects (p<0.01). Conclusion: Initiation of IFX therapy in patients with CD is associated with complete mucosal healing in 40% of patients. Scheduled IFX therapy results more likely in mucosal healing than episodic therapy. Mucosal healing was more often associated with clinical benefit.
P026 SAFETY OF ANTI-TNF THERAPY IN CROHN' S DISEASE: A META-ANALYSIS OF PLACEBO-CONTROLLED TRIALS L. Peyrin-Biroulet 1 , N. de Suray 1 , P. Deltenre 1 , W.J. Sandborn 2 , J.F. Colombel 1 . 1 University Hospital of Lille, Lille, France; 2 Mayo Clinic, Rochester, MN, United States Aim: The aim of this study was to assess the risk of malignancies, serious infections and deaths in patients treated with anti-TNF antibody therapies for Crohn' s disease by performing a meta-analysis. Materials and Methods: A systematic review of the literature was conducted in EMBASE, MEDLINE and Cochrane Library until June 2007. We selected the randomized placebo-controlled trials evaluating the effectiveness and the safety of anti-TNF antibodies (infliximab, adalimumab, certolizumab, CDP571, onercept and etanercept) in adult patients with Crohn' s disease. Statistical analysis was performed using the method of Der Simonian and Laird. We performed overall analysis and subgroup analysis regarding the design of the study (s hort-term induction trials, maintenance trials with randomization after open-label induction trials, short- and long-term induction trials). Results: A total of 21 randomized placebo-controlled were included for statistical analysis including 5356 patients: 3341 patients had received treatment with anti-TNF antibodies and 2015 patients received a placebo. In overall analysis, there was no statistically significant difference regarding the risk of serious infections (2,09 vs. 2,13%, p = 0.72), malignancies (0,24 vs. 0,39%, p = 0.39) and deaths (0,21 vs. 0,05%, p = 0.74) between patients treated with anti-TNF antibodies and those who received placebo. In subgroup analysis, risk of malignancies, serious infections or deaths was not statistically different compared to placebo in the 3 subgroups of trials. Conclusions: In clinical trials, the risk of serious infections, malignancies or deaths is not increased in patients with Crohn' s disease treated with anti-
P. Gionchetti, F. Rizzello, S. Laureti, R. Tambasco, F. Pierangeli, G. Poggioli, M. Campieri. University of Bologna, Bologna, Italy The occurrence of perianal lesions (PCD) greatly compromise the quality of life in Crohn' s disease (CD) patients. The major concern for both patients and clinicians is to avoid or delay proctectomy with a permanent oostomy that, when PCD is associated with a colonic involvement, have an OR of 2.1. Biological treatment alone helps to reduce the draining fistulas in 60% of patients, maintaining this results in 1/3 of patients after 1 year, but with a high number of treatment-related abscesses. Small series has shown that better results can be obtained when the biological treatment was performed after surgical evaluation (EUA) and drainage with seton placement. Aim of this study is to evaluate the efficacy of Infliximab in healing fistulas after a deep surgical sanitization of the perineum and loose seton placement. Patients and methods: 120 consecutive patients referred to our IBD clinic were included and 95 enrolled. Inclusions criteria were: age > 18 yrs, naïve to infliximab, active CD with colonic involvement, complex fistula with or without rectal inflammation, simple fistula with rectal inflammation; Exclusions criteria were: positive PPD test, simple fistulas without rectal inflammation, pregnancy or lactation. Healing was defined as the closure of the fistula tract with scare tissue; improvement was defined as the reduction of drainage without evidence of abscess or sepsis. Patients underwent EUA to correctly define the fistula tract and to sanitize the perineum; treatment with Infliximab 5mg/kg was started within ten days after surgery (wk 0, 2, 6 and every 8 wks until fistula closure or maximum 1yr). At week 10, and every 2 infliximab infusions, patients were evaluated surgically and with endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI), in order to evaluate response, presence of sepsis and timing to remove setons if needed. Results: Complete closure of fistulas tract should be confirmed by EUA and MRI. A complete closure of the fistula tract was obtained in 61 patients (64%), cessation of drainage in 18 (19%), non responders 13 (14%). Mean follow up was 24 months with a median number of infusions of 6 (range 4-10) and a median time to closure of 28 wks (range 14-54). Three patients had to discontinue the treatment for non serious infusion allergic reaction, and no abscesses treatment-related were reported. Conclusions: Our series reinforce the concept that a deep sanitization of the perineum is mandatory before to start biological treatment and assure a true healing of the fistula tract limiting the risk of a septic complication.
P028 UTILITY OF AZATHIOPRINE METABOLITES DETERMINATION DURING FOLLOW UP OF INFLAMMATORY BOWEL DISEASE PATIENTS AFTER STEROID TREATMENT WITHDRAWAL Y. González-Lama, on behalf of GETECCU (Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa). La Princesa Hospital, Madrid, Spain Aim: To establish the utility of 6-tioguanine (6-TGN) metabolites determination throughout follow up after steroid treatment withdrawal in inflammatory bowel disease patients treated with azathioprine (AZA) due to steroid resistance or dependence. Methods: Prospective and multicenter study in which 6-TGN levels of patients receiving AZA for steroid dependence or resistance were periodically monitored. Levels were measured during steroid treatment tapering and, after withdrawal, until an activity flare (persistence of steroid resistance or dependence) or for 6 months in those cases showing clinical response. Patients showing a thiopurine methyl-transferase (TPMT) activity below 5 U/ml were excluded. Results: 153 patients were included (mean age 36 years; 51% males; 73% Crohn' s disease; 27% ulcerative colitis). All the needed relevant information was obtained for 138 patients. TPMT ranged from 6.4 and 34 U/ml. Mean 6-TGN levels obtained at 2, 4 and 6 weeks as well as 2, 4, 6 months after steroid withdrawal were not significantly different between patients that at the time suffered a new flare and those who still maintained remission. Area under ROC curve relating 6-TGN levels and clinical response for each monitoring point was less than 0.7. No cut off point with useful sensitivity and specificity values was found. Conclusions: Systematic determination of 6-TGN levels throughout follow up of patients receiving AZA treatment due to steroid dependence or resistance is not useful to estimate punctual efficacy of the treatment at any monitoring point after steroid treatment withdrawal.
13
P025 MAINTENANCE Q8 THERAPY OF CROHN' S DISEASE WITH INFLIXIMAB IS ASSOCIATED WITH ENDOSCOPIC MUCOSAL HEALING IN THE LONG-TERM
TNF antibodies compared to placebo. These results must be confirmed in patients treated in clinical practice and with a longer follow-up.
F. Schnitzler, H. Fidder, M. Ferrante, M. Noman, G. Van Assche, I. Hoffman, S. Vermeire, P. Rutgeerts. University Hospital Leuven, Leuven, Belgium
P027 TREATMENT OF PERIANAL CROHN' S DISEASE WITH COMBINED SURGICAL AND BIOLOGICAL THERAPY
Introduction: The ACCENT I endoscopy substudy could demonstrate that maintenance therapy of Crohn' s disease (CD) with infliximab (IFX) q8 weeks is associated with mucosal healing over a 1 year period, leading to considerably fewer hospitalisations and surgeries. No data exist on the endoscopic outcome of IFX for CD long-term in clinical practice. Aims and methods: We studied mucosal healing during long-term treatment with IFX in a consecutive series of 614 CD patients, treated with IFX between 1995 and November 2007, by analyzing the reports from endoscopy performed during IFX treatment. Complete healing was defined as absence of ulcerations and partial healing as clear endoscopic improvement but still signs of inflammation. No healing was concluded in case of no endoscopic improvement. Results: During a median follow-up of 59 months (IQR 32-85), 8091 IFX infusions were administered. A total of 547 patients (89%) showed short term response whereas in 67 patients (10.9%) IFX had to be stopped for lack of response. In 388 patients, endoscopy was performed within a median of 1.61 months (IQR 0.16-8.91) prior to first IFX and 263 patients with initial response and further retreatment underwent endoscopy (1st endoscopy after start of IFX taken) after a median of 11.05 months (IQR 2.17-28.19) after start of IFX. IFX treatment in these patients was scheduled in 33.5%, episodic in 24.7% and episodic with switch to maintenance in 41.8%. More than two thirds (64.1%) were under concomitant immunomodulators (IM) and 35 patients received corticosteroids (CS). Overall, 61.2% of the 263 initial responders (n=161) showed mucosal healing, with 106 patients having full mucosal healing (40.3%) and 55 (20.9%) partial healing after a median of 4 IFX infusions (IQR 2-11). Patients with scheduled treatment from the start were more likely to show mucosal healing than patients who were started on episodic treatment (67/88 versus 94/175 respectively, p<0.0001, Odds ratio 2.75 (95%CI 1.55 - 4.88)). Concomitant IM had no influence on the healing rates (60.1% with IM vs. 59.8% without IM, p=0.96), whereas patients under CS had lower healing rates (15/35, 42.9%) than patients without CS (147/235, 62.6%, p=0.026). Of the patients showing sustained clinical benefit till end of FU (112/170), 65.9% had mucosal healing compared to 50% of patients (50/100) who had to stop IFX for loss of response or side effects (p<0.01). Conclusion: Initiation of IFX therapy in patients with CD is associated with complete mucosal healing in 40% of patients. Scheduled IFX therapy results more likely in mucosal healing than episodic therapy. Mucosal healing was more often associated with clinical benefit.
P026 SAFETY OF ANTI-TNF THERAPY IN CROHN' S DISEASE: A META-ANALYSIS OF PLACEBO-CONTROLLED TRIALS L. Peyrin-Biroulet 1 , N. de Suray 1 , P. Deltenre 1 , W.J. Sandborn 2 , J.F. Colombel 1 . 1 University Hospital of Lille, Lille, France; 2 Mayo Clinic, Rochester, MN, United States Aim: The aim of this study was to assess the risk of malignancies, serious infections and deaths in patients treated with anti-TNF antibody therapies for Crohn' s disease by performing a meta-analysis. Materials and Methods: A systematic review of the literature was conducted in EMBASE, MEDLINE and Cochrane Library until June 2007. We selected the randomized placebo-controlled trials evaluating the effectiveness and the safety of anti-TNF antibodies (infliximab, adalimumab, certolizumab, CDP571, onercept and etanercept) in adult patients with Crohn' s disease. Statistical analysis was performed using the method of Der Simonian and Laird. We performed overall analysis and subgroup analysis regarding the design of the study (s hort-term induction trials, maintenance trials with randomization after open-label induction trials, short- and long-term induction trials). Results: A total of 21 randomized placebo-controlled were included for statistical analysis including 5356 patients: 3341 patients had received treatment with anti-TNF antibodies and 2015 patients received a placebo. In overall analysis, there was no statistically significant difference regarding the risk of serious infections (2,09 vs. 2,13%, p = 0.72), malignancies (0,24 vs. 0,39%, p = 0.39) and deaths (0,21 vs. 0,05%, p = 0.74) between patients treated with anti-TNF antibodies and those who received placebo. In subgroup analysis, risk of malignancies, serious infections or deaths was not statistically different compared to placebo in the 3 subgroups of trials. Conclusions: In clinical trials, the risk of serious infections, malignancies or deaths is not increased in patients with Crohn' s disease treated with anti-
P. Gionchetti, F. Rizzello, S. Laureti, R. Tambasco, F. Pierangeli, G. Poggioli, M. Campieri. University of Bologna, Bologna, Italy The occurrence of perianal lesions (PCD) greatly compromise the quality of life in Crohn' s disease (CD) patients. The major concern for both patients and clinicians is to avoid or delay proctectomy with a permanent oostomy that, when PCD is associated with a colonic involvement, have an OR of 2.1. Biological treatment alone helps to reduce the draining fistulas in 60% of patients, maintaining this results in 1/3 of patients after 1 year, but with a high number of treatment-related abscesses. Small series has shown that better results can be obtained when the biological treatment was performed after surgical evaluation (EUA) and drainage with seton placement. Aim of this study is to evaluate the efficacy of Infliximab in healing fistulas after a deep surgical sanitization of the perineum and loose seton placement. Patients and methods: 120 consecutive patients referred to our IBD clinic were included and 95 enrolled. Inclusions criteria were: age > 18 yrs, naïve to infliximab, active CD with colonic involvement, complex fistula with or without rectal inflammation, simple fistula with rectal inflammation; Exclusions criteria were: positive PPD test, simple fistulas without rectal inflammation, pregnancy or lactation. Healing was defined as the closure of the fistula tract with scare tissue; improvement was defined as the reduction of drainage without evidence of abscess or sepsis. Patients underwent EUA to correctly define the fistula tract and to sanitize the perineum; treatment with Infliximab 5mg/kg was started within ten days after surgery (wk 0, 2, 6 and every 8 wks until fistula closure or maximum 1yr). At week 10, and every 2 infliximab infusions, patients were evaluated surgically and with endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI), in order to evaluate response, presence of sepsis and timing to remove setons if needed. Results: Complete closure of fistulas tract should be confirmed by EUA and MRI. A complete closure of the fistula tract was obtained in 61 patients (64%), cessation of drainage in 18 (19%), non responders 13 (14%). Mean follow up was 24 months with a median number of infusions of 6 (range 4-10) and a median time to closure of 28 wks (range 14-54). Three patients had to discontinue the treatment for non serious infusion allergic reaction, and no abscesses treatment-related were reported. Conclusions: Our series reinforce the concept that a deep sanitization of the perineum is mandatory before to start biological treatment and assure a true healing of the fistula tract limiting the risk of a septic complication.
P028 UTILITY OF AZATHIOPRINE METABOLITES DETERMINATION DURING FOLLOW UP OF INFLAMMATORY BOWEL DISEASE PATIENTS AFTER STEROID TREATMENT WITHDRAWAL Y. González-Lama, on behalf of GETECCU (Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa). La Princesa Hospital, Madrid, Spain Aim: To establish the utility of 6-tioguanine (6-TGN) metabolites determination throughout follow up after steroid treatment withdrawal in inflammatory bowel disease patients treated with azathioprine (AZA) due to steroid resistance or dependence. Methods: Prospective and multicenter study in which 6-TGN levels of patients receiving AZA for steroid dependence or resistance were periodically monitored. Levels were measured during steroid treatment tapering and, after withdrawal, until an activity flare (persistence of steroid resistance or dependence) or for 6 months in those cases showing clinical response. Patients showing a thiopurine methyl-transferase (TPMT) activity below 5 U/ml were excluded. Results: 153 patients were included (mean age 36 years; 51% males; 73% Crohn' s disease; 27% ulcerative colitis). All the needed relevant information was obtained for 138 patients. TPMT ranged from 6.4 and 34 U/ml. Mean 6-TGN levels obtained at 2, 4 and 6 weeks as well as 2, 4, 6 months after steroid withdrawal were not significantly different between patients that at the time suffered a new flare and those who still maintained remission. Area under ROC curve relating 6-TGN levels and clinical response for each monitoring point was less than 0.7. No cut off point with useful sensitivity and specificity values was found. Conclusions: Systematic determination of 6-TGN levels throughout follow up of patients receiving AZA treatment due to steroid dependence or resistance is not useful to estimate punctual efficacy of the treatment at any monitoring point after steroid treatment withdrawal.