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P069 A SINGLE CENTRE EXPERIENCE OF ADALIMUMAB TREATMENT IN PATIENTS WITH LUMINAL AND FISTULIZING CROHN'S DISEASE (CD): DO ANTIBODIES TO INFLIXIMAB (ATIs) AFFECT CLINICAL OUTCOME?
Abstracts of ECCO Congress, Innsbruck, Austria, 1—3 March 2007 P068 NATALIZUMAB MAINTAINS REMISSION FOR 2 YEARS IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE CROHN' S DISEASE AND IN THOSE WITH PRIOR INFLIXIMAB EXPOSURE: RESULTS FROM AN OPEN-LABEL EXTENSION STUDY G. D' Haens 1 , F. Baert 2 , P. Rutgeerts 3 , R. Panaccione 4 . 1 Imeldaziekenhuis; 2 H Hart Ziekenhuis; 3 Universitaire Ziekenhuizen; 4 University of Calgary Purpose: Natalizumab has been demonstrated as effective induction and maintenance therapy for moderately to severely active Crohn' s disease in clinical trials. Fifty-five percent of patients who responded to natalizumab were in remission (CDAI score <150) after 15 months of natalizumab therapy in the ENACT trials, compared with 22% in the placebo group (p<0.001). This analysis was undertaken to assess natalizumab' s ability to maintain remission for >2 years. Methods: Patients who completed ENACT-2 were eligible to enroll in an open-label (OL) study. The primary objective of this 2-year study was to examine natalizumab' s long-term safety and tolerability. Secondary efficacy endpoints included maintenance of remission. This analysis includes patients who were in remission after 15 months of natalizumab therapy in the ENACT trials who enrolled in the OL study and received an additional 12 months of natalizumab. Eighty-seven patients met the criteria for analysis; 22 with previous exposure to infliximab. Remission rates were calculated using last observation carried forward. Results: Patients in this analysis had a mean CDAI score of 151 (from a mean baseline CCDAI score of 292) after a single natalizumab infusion in ENACT-1. Ninety-three percent (81/87) of patients in remission at Month 12 of ENACT2 were in remission following 6 additional natalizumab infusions. After 12 additional infusions, 86% (75/87) were in remission. In patients with prior exposure to infliximab, 91% (20/22) were in remission after an additional 6 and 12 infusions. Similarly, 82% (9/11) who had previously failed infliximab were in remission at the same timepoints. Although not part of this analysis population, one patient in the OL study developed a fatal case of progressive multifocal leukoencephalopathy. Conclusions: Natalizumab maintained remission for >2 years when administered as continuous therapy. Patients who entered remission with natalizumab induction therapy were highly likely to maintain remission, including patients with prior infliximab failure.
P069 A SINGLE CENTRE EXPERIENCE OF ADALIMUMAB TREATMENT IN PATIENTS WITH LUMINAL AND FISTULIZING CROHN' S DISEASE (CD): DO ANTIBODIES TO INFLIXIMAB (ATIs) AFFECT CLINICAL OUTCOME? R.L. West 1 , E.J. Kuipers 1 , P. van der Toorn 1 , E. Buster 1 , P.B.F. Mensink 1 , G.J. Wolbink 2 , C.J. van der Woude 1 . 1 Erasmus MC University Medical Center Rotterdam; 2 Sanquin Research Amsterdam Purpose: Infliximab is an effective treatment for CD. However, ATIs can lead to allergic reactions or loss of efficacy. Adalimumab is thought to be effective in these patients. However, the effect of ATIs on treatment with adalimumab is unknown. The aim of this study was to assess the efficacy of adalimumab in patients with luminal or fistulizing CD and to determine whether ATIs affect treatment outcome. Methods: Patients with active luminal or fistulizing CD who failed to respond or were intolerant to infliximab were treated with adalimumab. The following subcutaneous regimen was used: 160 mg at week 0, 80 mg at week 2 and 40 mg every 2 weeks. Clinical response and side effects were assessed. Prior to treatment ATIs were determined in all patients. Results: In total 19 patients (M/F (3/16), median age 36 yrs, range 22-50) were included: 12 with luminal and 7 with fistulizing CD. Infliximab treatment was stopped due to non-response in 5 and due to intolerance to infliximab in 14 patients. Median duration of adalimumab treatment was 156 days (range 30-303). In patients with luminal CD clinical response was 50% (6/12) and in patients with fistulizing CD 85% (6/7). Older age independently predicted non-response (OR=0.81 for a 1-year increase in age, 95% CI: 0.59-0.99, p=0.038). Side effects were seen in 32% of patients (6/19). ATIs were present in 58% of patients (11/19) of which 55% (6/11) were nonresponders and 45% (5/11) developed side effects. The presence of ATIs tended to decrease response rates (p=0.147) and result in intolerance to adalimumab (p=0.177). Conclusions: Adalimumab is mainly well tolerated and is an effective treatment in CD, particularly for fistulizing CD. Older age is an independent predictor of non-response to adalimumab. Furthermore, the presence of ATIs tended to be associated with non-response and the occurrence of side effects.
21 P070 WIRLESS CAPSULE ENDOSCOPY IN CROHN' S DISEASE: CLINICAL RELEVANCE OF UPPER GI LESIONS AND FEASIBILITY 2 YEARS AFTER ILEO-COLONIC RESECTION L. Biancone, C. Petruzziello, E. Calabrese, G. Del Vecchio Blanco, S. Onali, M. Cossignani, G. Sica, F. Pallone. Università Tor Vergata, Roma Introduction: Capsule endoscopy (CE) is able to visualize small bowel lesions in Crohn' s disease(CD). The clinical relevance of upper gastrointestinal (UGI) lesions detected by CE in CD is unknown. Undefined is the feasibility of CE in CD after surgery. Aim: Primary endpoint was to assess, in a prospective longitudinal study, the clinical relevance of UGI lesions detected by CE in CD pts. 1 year after ileocolonic resection. Secondary endpoint was to evaluate, in the same cohort, the feasibility of CE 2 years after surgery. Materials and methods: 18 CD pts. undergoing ileo-colonic resection were followed up. Group A. At 1 year, all 18 pts. underwent colonoscopy, followed by CE in absence of strictures. Lesions at CE were separately assessed in the peri-anastomotic (PA)-area and in the UGI and graded: absent (G0), erythema/loss of villi (G1), erosions/aphtoid ulcers (G2), deep ulcers (G3) by 2 observers. At 1 yr, clinical activity (CDAI), epigastralgia, Hb, serum iron and ferritin were recorded. Group B. The same 18 pts. were followed up, with small bowel follow throught (SBFT) at 2 yrs. Results: Group A. At 1 yr, all 18 pts. were in remission without strictures. CE was performed in 17/18 pts. UGI lesions were detected in 8/17 (G2: 7, G3:1), 2/8 pts referring epigastralgia, with anaemia in 1. In the 9 pts with no upper lesions, 1 pt. had epigastralgia, 6 anaemia. Interobserver agreement was very good for the UGI lesions (k=0.859), good for PA-lesions (k=0.611). Group B. At 2 yrs, SBFT was performed in 12/18 pts. In 9/12 pts.(all in remission) SBFT showed strictures, contraindicating CE. Conclusions: In CD UGI lesions detected by CE may have no clinical relevance. 2 years after resection, CE is not recommended in the majority of CD pts, due to the risk of impact related to asymptomatic strictures.
P071 RISK FACTORS ASSOCIATED WITH SMALL BOWEL ADENOCARCINOMA IN CROHN' S DISEASE: A CASE-CONTROL STUDY G. Piton 1 , J. Cosnes 2 , E. Monnet 1 , L. Beaugerie 2, G. Savoye 3 , G. Cadiot 4 , B. Flourie 5 , M. Lemann 6 , J.-F. Colombel 7 , P. Marteau 8 , F. Carbonnel 1 . 1 Centre Hospitalier Universitaire de Besançon; 2 APHP, Hôpital Saint-Antoine, Paris; 3 Centre Hospitalier Universitaire de Rouen; 4 Centre Hospitalier Universitaire de Reims; 5 Centre Hospitalier Universitaire de Lyon; 6 APHP, Hôpital Saint-Louis, Paris; 7 Centre Hospitalier Universitaire de Lille; 8 APHP, Hôpital Européen Georges Pompidou, Paris Background & Aims: Crohn' s Disease (CD) is associated with an increased risk of small bowel adenocarcinoma (SBA). SBA accounts for 30 to 50% of gastrointestinal cancer during CD [1]. Risk factors remain ill-defined. The aim of this study was to define risk factors of SBA during CD. Methods: 29 patients with CD and SBA were identified, and matched for sex, age, duration and site of CD, to 87 controls with CD without SBA, recruited in a single center. Variables studied in cases and controls were professional status; tobacco; cholecystectomy; appendectomy; familial history of IBD; Montreal Classification 5 years after the diagnosis of CD, 3 years before the date of SBA, and at the time of SBA; extraintestinal manifestations; granuloma; variables of treatment (salicylates, steroids, immunosuppressive, intestinal resection for CD) were studied in the 21 cases (and respective controls) whose CD duration at diagnosis of SBA was longer than one year. Conditional logistic regression identified variables independently associated to SBA. Results: In univariate analysis, cases had had significantly less intestinal resection and had received less salicylates (median duration 2 years) [respectively OR (IC 95%) 0.07 (0.02-0.33) and 0.32 (0.11-0.88)] than controls. Moreover, median duration (min-max) of CD without intestinal resection was significantly longer in cases [15,9 years (1,4-37,1)] than controls [8,2 years (0,1-35,8), p=0,02]. In multivariate analysis, two risk factors were associated with a lower risk of SBA: intestinal resection and salicylates during more than 2 years [respectively OR=0.04 (0.01-0.31) and OR=0.12 (0.02-0.69)]. These factors remained significant in the subgroup of cases (n=14) and controls (n=42) who came from the center in which controls were recruited. Conclusions: This study suggests that intestinal resection and salicylates therapy of more than 2 years reduce the risk of SBA in patients with CD. Reference: [1] Jess T et al. Alim Pharmacol Ther 2004;19:287-93.
P069 A SINGLE CENTRE EXPERIENCE OF ADALIMUMAB TREATMENT IN PATIENTS WITH LUMINAL AND FISTULIZING CROHN' S DISEASE (CD): DO ANTIBODIES TO INFLIXIMAB (ATIs) AFFECT CLINICAL OUTCOME? R.L. West 1 , E.J. Kuipers 1 , P. van der Toorn 1 , E. Buster 1 , P.B.F. Mensink 1 , G.J. Wolbink 2 , C.J. van der Woude 1 . 1 Erasmus MC University Medical Center Rotterdam; 2 Sanquin Research Amsterdam Purpose: Infliximab is an effective treatment for CD. However, ATIs can lead to allergic reactions or loss of efficacy. Adalimumab is thought to be effective in these patients. However, the effect of ATIs on treatment with adalimumab is unknown. The aim of this study was to assess the efficacy of adalimumab in patients with luminal or fistulizing CD and to determine whether ATIs affect treatment outcome. Methods: Patients with active luminal or fistulizing CD who failed to respond or were intolerant to infliximab were treated with adalimumab. The following subcutaneous regimen was used: 160 mg at week 0, 80 mg at week 2 and 40 mg every 2 weeks. Clinical response and side effects were assessed. Prior to treatment ATIs were determined in all patients. Results: In total 19 patients (M/F (3/16), median age 36 yrs, range 22-50) were included: 12 with luminal and 7 with fistulizing CD. Infliximab treatment was stopped due to non-response in 5 and due to intolerance to infliximab in 14 patients. Median duration of adalimumab treatment was 156 days (range 30-303). In patients with luminal CD clinical response was 50% (6/12) and in patients with fistulizing CD 85% (6/7). Older age independently predicted non-response (OR=0.81 for a 1-year increase in age, 95% CI: 0.59-0.99, p=0.038). Side effects were seen in 32% of patients (6/19). ATIs were present in 58% of patients (11/19) of which 55% (6/11) were nonresponders and 45% (5/11) developed side effects. The presence of ATIs tended to decrease response rates (p=0.147) and result in intolerance to adalimumab (p=0.177). Conclusions: Adalimumab is mainly well tolerated and is an effective treatment in CD, particularly for fistulizing CD. Older age is an independent predictor of non-response to adalimumab. Furthermore, the presence of ATIs tended to be associated with non-response and the occurrence of side effects.
21 P070 WIRLESS CAPSULE ENDOSCOPY IN CROHN' S DISEASE: CLINICAL RELEVANCE OF UPPER GI LESIONS AND FEASIBILITY 2 YEARS AFTER ILEO-COLONIC RESECTION L. Biancone, C. Petruzziello, E. Calabrese, G. Del Vecchio Blanco, S. Onali, M. Cossignani, G. Sica, F. Pallone. Università Tor Vergata, Roma Introduction: Capsule endoscopy (CE) is able to visualize small bowel lesions in Crohn' s disease(CD). The clinical relevance of upper gastrointestinal (UGI) lesions detected by CE in CD is unknown. Undefined is the feasibility of CE in CD after surgery. Aim: Primary endpoint was to assess, in a prospective longitudinal study, the clinical relevance of UGI lesions detected by CE in CD pts. 1 year after ileocolonic resection. Secondary endpoint was to evaluate, in the same cohort, the feasibility of CE 2 years after surgery. Materials and methods: 18 CD pts. undergoing ileo-colonic resection were followed up. Group A. At 1 year, all 18 pts. underwent colonoscopy, followed by CE in absence of strictures. Lesions at CE were separately assessed in the peri-anastomotic (PA)-area and in the UGI and graded: absent (G0), erythema/loss of villi (G1), erosions/aphtoid ulcers (G2), deep ulcers (G3) by 2 observers. At 1 yr, clinical activity (CDAI), epigastralgia, Hb, serum iron and ferritin were recorded. Group B. The same 18 pts. were followed up, with small bowel follow throught (SBFT) at 2 yrs. Results: Group A. At 1 yr, all 18 pts. were in remission without strictures. CE was performed in 17/18 pts. UGI lesions were detected in 8/17 (G2: 7, G3:1), 2/8 pts referring epigastralgia, with anaemia in 1. In the 9 pts with no upper lesions, 1 pt. had epigastralgia, 6 anaemia. Interobserver agreement was very good for the UGI lesions (k=0.859), good for PA-lesions (k=0.611). Group B. At 2 yrs, SBFT was performed in 12/18 pts. In 9/12 pts.(all in remission) SBFT showed strictures, contraindicating CE. Conclusions: In CD UGI lesions detected by CE may have no clinical relevance. 2 years after resection, CE is not recommended in the majority of CD pts, due to the risk of impact related to asymptomatic strictures.
P071 RISK FACTORS ASSOCIATED WITH SMALL BOWEL ADENOCARCINOMA IN CROHN' S DISEASE: A CASE-CONTROL STUDY G. Piton 1 , J. Cosnes 2 , E. Monnet 1 , L. Beaugerie 2, G. Savoye 3 , G. Cadiot 4 , B. Flourie 5 , M. Lemann 6 , J.-F. Colombel 7 , P. Marteau 8 , F. Carbonnel 1 . 1 Centre Hospitalier Universitaire de Besançon; 2 APHP, Hôpital Saint-Antoine, Paris; 3 Centre Hospitalier Universitaire de Rouen; 4 Centre Hospitalier Universitaire de Reims; 5 Centre Hospitalier Universitaire de Lyon; 6 APHP, Hôpital Saint-Louis, Paris; 7 Centre Hospitalier Universitaire de Lille; 8 APHP, Hôpital Européen Georges Pompidou, Paris Background & Aims: Crohn' s Disease (CD) is associated with an increased risk of small bowel adenocarcinoma (SBA). SBA accounts for 30 to 50% of gastrointestinal cancer during CD [1]. Risk factors remain ill-defined. The aim of this study was to define risk factors of SBA during CD. Methods: 29 patients with CD and SBA were identified, and matched for sex, age, duration and site of CD, to 87 controls with CD without SBA, recruited in a single center. Variables studied in cases and controls were professional status; tobacco; cholecystectomy; appendectomy; familial history of IBD; Montreal Classification 5 years after the diagnosis of CD, 3 years before the date of SBA, and at the time of SBA; extraintestinal manifestations; granuloma; variables of treatment (salicylates, steroids, immunosuppressive, intestinal resection for CD) were studied in the 21 cases (and respective controls) whose CD duration at diagnosis of SBA was longer than one year. Conditional logistic regression identified variables independently associated to SBA. Results: In univariate analysis, cases had had significantly less intestinal resection and had received less salicylates (median duration 2 years) [respectively OR (IC 95%) 0.07 (0.02-0.33) and 0.32 (0.11-0.88)] than controls. Moreover, median duration (min-max) of CD without intestinal resection was significantly longer in cases [15,9 years (1,4-37,1)] than controls [8,2 years (0,1-35,8), p=0,02]. In multivariate analysis, two risk factors were associated with a lower risk of SBA: intestinal resection and salicylates during more than 2 years [respectively OR=0.04 (0.01-0.31) and OR=0.12 (0.02-0.69)]. These factors remained significant in the subgroup of cases (n=14) and controls (n=42) who came from the center in which controls were recruited. Conclusions: This study suggests that intestinal resection and salicylates therapy of more than 2 years reduce the risk of SBA in patients with CD. Reference: [1] Jess T et al. Alim Pharmacol Ther 2004;19:287-93.