- Email: [email protected]
13 - WELCOME: A randomized, double-blind, controlled trial comparing certolizumab pegol 400mg every 2 weeks with every 4 weeks for maintenance of response and remission in patients with moderate-to-severe Crohn's disease with secondary failure to infliximab
S8
Oral Presentations
were periodically monitored during steroid tapering and, after withdrawal, until a new activity flare (persistence of steroid resistance or dependence), or for 6 months in those showing maintenance of clinical response. Thiopurine methyltransferase (TPMT) activity above 5 U/ml was required. Results: 153 patients were included, and 140 finished the study. Mean age was 36 years (range 16 77), 50% were males, and 72% had Crohn’s disease. Mean 6TGN levels (and the ratios 6TGN/6MMPR, 6TGN/TPMT) obtained at basal, 2 weeks, and 1, 2, 4 and 6 months after steroid withdrawal were not significantly different between patients that were or were not in clinical remission at each visit. The area under the ROC curve (AUC) evaluating the accuracy of 6TGN levels for the diagnosis of clinical response for each monitoring point was less than 0.7. No cut-off point with useful sensitivity/specificity values was found, including 230 or 260 pmol/8×108 (that are commonly proposed in the literature). The AUC assessing the accuracy of the 6TGN determination at 2 weeks, 1, 2 or 4 months after starting AZA/MP to predict the response by the end of the follow-up was also less than 0.7. Once again, no useful cutoff point was found. Thiopurinic-related toxicity was detected in 9 cases (6.4%): No cases of hepatotoxicity were found, and only 3 cases of myelotoxicity were reported. No differences in 6TGN levels were found in patients suffering AZA-related toxicity. Specifically, 6TGN levels could not be related to the risk of developing myelotoxicity. Conclusions: Systematic quantification of thiopurinic metabolites (6TGN/6MMPR) in IBD patients receiving AZA/MP with the aim of predicting or assessing treatment response or safety cannot be recommended.
TST and QuantiFERON® is shown in the table. The median TST induration was 2.11 mm (±5.2) for the entire study population, 2.07 mm (±5) in pts with and 2.22 mm in pts without IS (±5.7) (p = 0.882), respectively. Among subjects with positive TST median induration was 12.5 mm (±5.3) in IS patients (n = 17) and 16 mm (±2.4) in pts without IS (n = 5) (p = 0.058). There was a significant higher number of positive QuantiFERON® results in patients without IS (p = 0.036). A positive result in any of the 3 tests prompted prophylactic therapy for LTB with isoniazid in 25/145 (17.2%) patients. No single case of TB reactivation was observed by now. Conclusion: Our results reveal significant influence of IS on TST and QuantiFERON® results in IBD patients undergoing screening for LTB. We speculate that with current guidelines for TB screening prior TNF alpha therapy the screening methods appear to be inaccurate in patients under IS. Therefore, LTB screening might be best performed before IS treatment.
12 Immunosuppressive (IS) therapy impacts the results of Quantiferon® and tuberculin skin test in routine screening for latent tuberculosis (LTB) in patients with inflammatory bowel diseases (IBD) P. Papay *, A. Eser, W. Miehsler, C. Lichtenberger, A. Mikulits, C. Dejaco, G. Novacek, H. Vogelsang, W. Reinisch. Medical University Vienna, University Clinic of Internal Medicine 3, Vienna, Austria
13 WELCOME: A randomized, double-blind, controlled trial comparing certolizumab pegol 400 mg every 2 weeks with every 4 weeks for maintenance of response and remission in patients with moderate-to-severe Crohn’s disease with secondary failure to infliximab
Introduction: Screening for LTB is part of the routine management in patients with IBD before starting therapy with Tumor Necrosis Factor (TNF) alpha inhibitors. Recently, the whole blood interferon gamma assay (QuantiFERON® ) emerged as additional test for routine screening usually consisting of tuberculin skin test (TST) and chest X-ray. However, in patients with immunosuppression (IS) both tests might show limitations. Aims and Methods: We aimed to compare results from QuantiFERON® and TST in consecutive IBD patients with or without IS with the indication of anti TNF alpha therapy. In pts under IS dose, duration and concomitant use of steroids, azathioprine, and 6-mercaptopurine, or previous use of infliximab were obtained. To date, 145 patients with IBD were screened for LTB by chest x-ray, TST and QuantiFERON® . Signs indicative of LTB from chest x-ray included granuloma, bihilar lymphadenopathy and pleura scarring. TST was assessed positive if induration 5 mm appeared after 48 72 h of intracutan application of tuberculin 2 units in 0.1 ml/ in immunosuppressed and 10 mm in all other IBD patients. QuantiFERON® was positive if quantitative measurement indicated 0.35 U/ml. Results: QuantiFERON® test failed on samples from 15/145 (10.3%) patients, resulting in 130/145 (89.7%) patients on whom results from all 3 screening tests were available. There were 109 pts (75.2%) with and 36 (24.8%) without IS. Seventy-six patients (52.4%) were under maintenance AZA/6-MP, 49 (33.7%) under steroids 10 mg daily for 2 weeks and 16 subjects (11%) received infliximab previously. The impact of IS therapy on
Table: Impact of IS on TST and QuantiFERON results Indeterminable
Pos
Neg
Indeterminable
TST
Pos
IGRA
Neg
n = 145
IS 92(84.4%) 6(5.5%) 11(10.1%) 92(84.4%) 17(15.6%) 109(75.2%) No IS 25(69.4%) 7(19.4%) 4(11.1%) 31(86.1%) 5(13.9%) 36(24.8%) Unknown 117(80.7%) 13(8.9%) 15(10.3%) 123(84.8%) 22(15.2%)
W.J. Sandborn1 *, S. Vermeire2 , G. D’Haens3 , J.F. Colombel4 , R.N. Fedorak5 , M.E. Spehlmann6 , M.T. Abreu7 , K. Mitchev8 , C. Jamoul8 , P. Rutgeerts2 . 1 Mayo Clinic, Rochester, MN, USA, 2 University Hospital Gasthuisberg, Leuven, Belgium, 3 Imelda General Hospital, Bonheiden, Belgium, 4 CHU Lille, Lille, France, 5 University of Alberta, Edmonton, AB, Canada, 6 University of California, San Diego, CA, USA, 7 University of Miami, Miami, FL, USA, 8 UCB, Braine l’Alleud, Belgium Aim: Approximately 40% of patients with Crohn’s disease (CD) who respond to anti-tumor necrosis factor a (TNFa) therapy will lose response or experience treatment-limiting immunemediated reactions to individual anti-TNFs. A prior study showed that certolizumab pegol (CZP) 400 mg every 4 weeks (q4w) is effective for maintenance of response and remission in patients with CD who were naive to infliximab (IFX) or who had previously received IFX. The objective was to compare the efficacy and safety of certolizumab pegol (CZP) 400 mg every 2 weeks (q2w) with every 4 weeks (q4w) for maintenance of clinical response and remission in patients with moderate-to-severe CD who had previously lost response or developed hypersensitivity to infliximab (IFX) and had responded to induction therapy with CZP. Materials and Methods: WELCOME was a 26-week, Phase IIIb, multicenter trial, consisting of 6-weeks open-label induction followed by a double-blind randomized maintenance phase in responders. Adult patients with a CD Activity Index (CDAI) score 220 450 and a history of secondary IFX failure (loss of response or development of acute or delayed hypersensitivity reactions) received open-label induction with CZP 400 mg subcutaneous (sc) injections at Weeks 0, 2, and 4. Non-responders at Week 6 were withdrawn. Those who were in clinical response at Week 6
Abstracts of the 4th Congress of ECCO
the European Crohn’s and Colitis Organisation
were randomized to receive maintenance therapy with CZP 400 mg sc q2w or q4w through Week 24. Clinical response was defined as 100-point decrease from baseline in CDAI and remission as a CDAI score of 150 points. Results: At week 6, 62.0% (334/539) of patients who received open-label induction therapy with CZP were in clinical response. Of these responders, 329 entered the double-blind maintenance trial and were thus included in the modified intent-to-treat population (CZP q2w, n = 161; CZP q4w, n = 168). Clinical response and remission rates at Week 26 are shown in the table. There was no significant difference between q2w or q4w CZP dosing regimens with respect to response (CDAI decrease of 100 or 70 points from baseline [P = 0.55 and P = 0.74, respectively] or remission rates [P = 0.81]). No new safety signals were observed. Week 26 CDAI 100 point decrease CDAI 70 point decrease CDAI 150 points
CZP, % patients q2w (n = 161)
q4w (n = 168)
36.6 41.0 30.4
39.9 42.9 29.2
Conclusions: Sixty-two percent of patients with moderateto-severe CD who had previously responded to IFX and lost response or developed hypersensitivity responded to open-label induction therapy with CZP. Among patients who responded to induction therapy with CZP, continuing therapy with CZP 400 mg q4w is as effective as CZP 400 mg q2w for maintenance of response and remission at Week 26. 14 Clinical course and cost of care in ulcerative colitis: Markov chain analysis of a European prospective population-based cohort S. Odes1 *, H. Vardi2 , M. Friger2 , P. Munkholm3 , D. Esser4 , M. Elkjær3 , H. Waters5 , E. Langholz6 . 1 Gastroenterology Department, Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel, 2 Epidemiology Department, Ben Gurion University of the Negev, Beer Sheva, Israel, 3 Gastroenterology Department, Herlev Hospital and University of Copenhagen, Copenhagen, Denmark, 4 Centocor BV, Leiden, Netherlands, 5 Centocor Ortho Biotech Services, Malvern, PA, USA, 6 Gastroenterology Department, Gentofte Hospital and University of Copenhagen, Copenhagen, Denmark Introduction: Predicting the clinical and economic outcome is difficult in ulcerative colitis, with its recurring-remitting course over many years, competing risk factors and multiple possible consequences. The Markov chain, a stochastic process with the Markov assumption, is an increasingly used approach in outcomes-analysis in complex disease. Methods: The European Collaborative Study of Inflammatory Bowel Disease (EC-IBD) Group incepted European and Israeli patients prospectively at diagnosis of ulcerative colitis from 1991 to 1993. Patients having more than 5 years unbroken tracking from diagnosis within a 10-year time horizon were grouped into clinical transition states by: (1) medical and surgical therapies recorded in continuous quarter-year cycles, (2) presence of flare-years in a minority (<50%) or majority (>50%) of the follow-up years (hereafter called “minority flare-years” patients or “majority flare-years” patients respectively). Clinical course transition states (graded by treatment) were calculated by a Markov model (SPSS 16, STATA 10.1). The 5 transition states were defined as follows: “remission” (symptomatic treatment), “mild-moderate” (local corticosteroids, budesonide, mesalazine, antibiotics), “severe” (systemic steroids, immunosuppression, biologics), surgery (abdominal and pouch surgery), and death (from ulcerative
S9
colitis). Healthcare costs per patient per cycle were matched to the transition states. Results: 705 patients had 39208 cycles. In 644 cases with minority flare-years, the probability (expressed per cycle) of worsening (to a more severe state or surgery or death) of the “remission state” was 0.0811, of “mild-moderate state” 0.0763, of “severe state” 0.2664. In 61 cases with majority flare-years, the probability of worsening of the “remission state” was 0.2980, of “mild-moderate state” 0.1432, of “severe state” 0.2733. Minority flare-year patients in the initial “surgery state” had probabilities of 0.3291 for subsequent mild disease and 0.3924 for severe disease (pouchitis), and 0.0506 for pouch removal; majority flare-year patients had probabilities 0.3750 for mild or severe disease (pouchitis). The subsequent “surgery state” in the minority flare-years group acquired cases mostly from “surgery” (patients postcolectomy requiring pouch removal, probability 0.0506), and in the majority flare-years group from “severe” disease (patients requiring colectomy, probability 0.0104). Mean healthcare costs (euros/patient-cycle) were as follows: remission 93, mildmoderate 267, severe 939, surgery 8623, death 655. Surgery accounted for 72% of costs in year 1, and 83% in follow-up year 10. Conclusions: Severe ulcerative colitis has an inferior prognosis and high healthcare costs, with surgery accounting for the greatest expense. There is a considerable probability of pouchitis after surgery. Medical treatments must aim therefore to maintain patients in remission and avoid the need for surgical operations. 15 Laparoscopic-assisted versus open ileocolic resection for Crohn’s disease: long term results of a prospective randomized trial E.J. Eshuis1 *, J.F.M. Slors1 , M.A. Cuesta2 , R.E.G. Pierik3 , P.C.F. Stokkers1 , M.A.G. Sprangers1 , W.A. Bemelman1 . 1 Academic Medical Center, Amsterdam, Netherlands, 2 Free University Medical Center, Amsterdam, Netherlands, 3 Isala Clinics, Zwolle, Netherlands Aim: Four meta-analyses exist evaluating the short term results of laparoscopic versus open ileocolic resection for Crohn’s disease. Little is known about the long term results of both procedures with respect to surgical recurrence rate, overall reoperation rate, incidence of incisional hernia, adhesive small bowel obstruction, quality of life (QOL) and Body Image (BI) and cosmesis. The objective of this study is to determine the long term results of a randomized multicenter study comparing laparoscopic with open ileocolic resection for Crohn’s disease. Materials and Methods: Sixty patients who participated in this trial were prospectively followed in the outpatient clinic. Patients had an ileocolic resection between 1999 and 2003. Primary outcome parameters were overall reoperation and readmission rate and re-resection rate for recurrent Crohn’s disease. Secondary outcomes were QOL, BI and cosmesis. Results: Five patients, 1 from the laparoscopic group and 4 from the open group were lost to follow up. The groups were comparable for characteristics as sex, age, and maintenance therapy. Mean follow-up was 6.8 years. Overall, 16/29 (55%) and 16/26 (62%) patients remained relapse-free after the ileocolic resection in the laparoscopic and open group respectively ( p = NS). Resection of recurrent Crohn’s disease occurred in 2/29 (7%) and 3/26 (12%) patients ( p = NS). Two reoperations for incisional hernia were done in the open group (2/26 [8%]) vs. nil in the laparoscopic group. Reoperation for adhesive small bowel obstruction was done twice in the open group (2/26 [8%]) vs. nil in the laparoscopic group. Overall reoperation rate was 2/29 (7%) versus 7/26 (27%)
Oral Presentations
were periodically monitored during steroid tapering and, after withdrawal, until a new activity flare (persistence of steroid resistance or dependence), or for 6 months in those showing maintenance of clinical response. Thiopurine methyltransferase (TPMT) activity above 5 U/ml was required. Results: 153 patients were included, and 140 finished the study. Mean age was 36 years (range 16 77), 50% were males, and 72% had Crohn’s disease. Mean 6TGN levels (and the ratios 6TGN/6MMPR, 6TGN/TPMT) obtained at basal, 2 weeks, and 1, 2, 4 and 6 months after steroid withdrawal were not significantly different between patients that were or were not in clinical remission at each visit. The area under the ROC curve (AUC) evaluating the accuracy of 6TGN levels for the diagnosis of clinical response for each monitoring point was less than 0.7. No cut-off point with useful sensitivity/specificity values was found, including 230 or 260 pmol/8×108 (that are commonly proposed in the literature). The AUC assessing the accuracy of the 6TGN determination at 2 weeks, 1, 2 or 4 months after starting AZA/MP to predict the response by the end of the follow-up was also less than 0.7. Once again, no useful cutoff point was found. Thiopurinic-related toxicity was detected in 9 cases (6.4%): No cases of hepatotoxicity were found, and only 3 cases of myelotoxicity were reported. No differences in 6TGN levels were found in patients suffering AZA-related toxicity. Specifically, 6TGN levels could not be related to the risk of developing myelotoxicity. Conclusions: Systematic quantification of thiopurinic metabolites (6TGN/6MMPR) in IBD patients receiving AZA/MP with the aim of predicting or assessing treatment response or safety cannot be recommended.
TST and QuantiFERON® is shown in the table. The median TST induration was 2.11 mm (±5.2) for the entire study population, 2.07 mm (±5) in pts with and 2.22 mm in pts without IS (±5.7) (p = 0.882), respectively. Among subjects with positive TST median induration was 12.5 mm (±5.3) in IS patients (n = 17) and 16 mm (±2.4) in pts without IS (n = 5) (p = 0.058). There was a significant higher number of positive QuantiFERON® results in patients without IS (p = 0.036). A positive result in any of the 3 tests prompted prophylactic therapy for LTB with isoniazid in 25/145 (17.2%) patients. No single case of TB reactivation was observed by now. Conclusion: Our results reveal significant influence of IS on TST and QuantiFERON® results in IBD patients undergoing screening for LTB. We speculate that with current guidelines for TB screening prior TNF alpha therapy the screening methods appear to be inaccurate in patients under IS. Therefore, LTB screening might be best performed before IS treatment.
12 Immunosuppressive (IS) therapy impacts the results of Quantiferon® and tuberculin skin test in routine screening for latent tuberculosis (LTB) in patients with inflammatory bowel diseases (IBD) P. Papay *, A. Eser, W. Miehsler, C. Lichtenberger, A. Mikulits, C. Dejaco, G. Novacek, H. Vogelsang, W. Reinisch. Medical University Vienna, University Clinic of Internal Medicine 3, Vienna, Austria
13 WELCOME: A randomized, double-blind, controlled trial comparing certolizumab pegol 400 mg every 2 weeks with every 4 weeks for maintenance of response and remission in patients with moderate-to-severe Crohn’s disease with secondary failure to infliximab
Introduction: Screening for LTB is part of the routine management in patients with IBD before starting therapy with Tumor Necrosis Factor (TNF) alpha inhibitors. Recently, the whole blood interferon gamma assay (QuantiFERON® ) emerged as additional test for routine screening usually consisting of tuberculin skin test (TST) and chest X-ray. However, in patients with immunosuppression (IS) both tests might show limitations. Aims and Methods: We aimed to compare results from QuantiFERON® and TST in consecutive IBD patients with or without IS with the indication of anti TNF alpha therapy. In pts under IS dose, duration and concomitant use of steroids, azathioprine, and 6-mercaptopurine, or previous use of infliximab were obtained. To date, 145 patients with IBD were screened for LTB by chest x-ray, TST and QuantiFERON® . Signs indicative of LTB from chest x-ray included granuloma, bihilar lymphadenopathy and pleura scarring. TST was assessed positive if induration 5 mm appeared after 48 72 h of intracutan application of tuberculin 2 units in 0.1 ml/ in immunosuppressed and 10 mm in all other IBD patients. QuantiFERON® was positive if quantitative measurement indicated 0.35 U/ml. Results: QuantiFERON® test failed on samples from 15/145 (10.3%) patients, resulting in 130/145 (89.7%) patients on whom results from all 3 screening tests were available. There were 109 pts (75.2%) with and 36 (24.8%) without IS. Seventy-six patients (52.4%) were under maintenance AZA/6-MP, 49 (33.7%) under steroids 10 mg daily for 2 weeks and 16 subjects (11%) received infliximab previously. The impact of IS therapy on
Table: Impact of IS on TST and QuantiFERON results Indeterminable
Pos
Neg
Indeterminable
TST
Pos
IGRA
Neg
n = 145
IS 92(84.4%) 6(5.5%) 11(10.1%) 92(84.4%) 17(15.6%) 109(75.2%) No IS 25(69.4%) 7(19.4%) 4(11.1%) 31(86.1%) 5(13.9%) 36(24.8%) Unknown 117(80.7%) 13(8.9%) 15(10.3%) 123(84.8%) 22(15.2%)
W.J. Sandborn1 *, S. Vermeire2 , G. D’Haens3 , J.F. Colombel4 , R.N. Fedorak5 , M.E. Spehlmann6 , M.T. Abreu7 , K. Mitchev8 , C. Jamoul8 , P. Rutgeerts2 . 1 Mayo Clinic, Rochester, MN, USA, 2 University Hospital Gasthuisberg, Leuven, Belgium, 3 Imelda General Hospital, Bonheiden, Belgium, 4 CHU Lille, Lille, France, 5 University of Alberta, Edmonton, AB, Canada, 6 University of California, San Diego, CA, USA, 7 University of Miami, Miami, FL, USA, 8 UCB, Braine l’Alleud, Belgium Aim: Approximately 40% of patients with Crohn’s disease (CD) who respond to anti-tumor necrosis factor a (TNFa) therapy will lose response or experience treatment-limiting immunemediated reactions to individual anti-TNFs. A prior study showed that certolizumab pegol (CZP) 400 mg every 4 weeks (q4w) is effective for maintenance of response and remission in patients with CD who were naive to infliximab (IFX) or who had previously received IFX. The objective was to compare the efficacy and safety of certolizumab pegol (CZP) 400 mg every 2 weeks (q2w) with every 4 weeks (q4w) for maintenance of clinical response and remission in patients with moderate-to-severe CD who had previously lost response or developed hypersensitivity to infliximab (IFX) and had responded to induction therapy with CZP. Materials and Methods: WELCOME was a 26-week, Phase IIIb, multicenter trial, consisting of 6-weeks open-label induction followed by a double-blind randomized maintenance phase in responders. Adult patients with a CD Activity Index (CDAI) score 220 450 and a history of secondary IFX failure (loss of response or development of acute or delayed hypersensitivity reactions) received open-label induction with CZP 400 mg subcutaneous (sc) injections at Weeks 0, 2, and 4. Non-responders at Week 6 were withdrawn. Those who were in clinical response at Week 6
Abstracts of the 4th Congress of ECCO
the European Crohn’s and Colitis Organisation
were randomized to receive maintenance therapy with CZP 400 mg sc q2w or q4w through Week 24. Clinical response was defined as 100-point decrease from baseline in CDAI and remission as a CDAI score of 150 points. Results: At week 6, 62.0% (334/539) of patients who received open-label induction therapy with CZP were in clinical response. Of these responders, 329 entered the double-blind maintenance trial and were thus included in the modified intent-to-treat population (CZP q2w, n = 161; CZP q4w, n = 168). Clinical response and remission rates at Week 26 are shown in the table. There was no significant difference between q2w or q4w CZP dosing regimens with respect to response (CDAI decrease of 100 or 70 points from baseline [P = 0.55 and P = 0.74, respectively] or remission rates [P = 0.81]). No new safety signals were observed. Week 26 CDAI 100 point decrease CDAI 70 point decrease CDAI 150 points
CZP, % patients q2w (n = 161)
q4w (n = 168)
36.6 41.0 30.4
39.9 42.9 29.2
Conclusions: Sixty-two percent of patients with moderateto-severe CD who had previously responded to IFX and lost response or developed hypersensitivity responded to open-label induction therapy with CZP. Among patients who responded to induction therapy with CZP, continuing therapy with CZP 400 mg q4w is as effective as CZP 400 mg q2w for maintenance of response and remission at Week 26. 14 Clinical course and cost of care in ulcerative colitis: Markov chain analysis of a European prospective population-based cohort S. Odes1 *, H. Vardi2 , M. Friger2 , P. Munkholm3 , D. Esser4 , M. Elkjær3 , H. Waters5 , E. Langholz6 . 1 Gastroenterology Department, Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel, 2 Epidemiology Department, Ben Gurion University of the Negev, Beer Sheva, Israel, 3 Gastroenterology Department, Herlev Hospital and University of Copenhagen, Copenhagen, Denmark, 4 Centocor BV, Leiden, Netherlands, 5 Centocor Ortho Biotech Services, Malvern, PA, USA, 6 Gastroenterology Department, Gentofte Hospital and University of Copenhagen, Copenhagen, Denmark Introduction: Predicting the clinical and economic outcome is difficult in ulcerative colitis, with its recurring-remitting course over many years, competing risk factors and multiple possible consequences. The Markov chain, a stochastic process with the Markov assumption, is an increasingly used approach in outcomes-analysis in complex disease. Methods: The European Collaborative Study of Inflammatory Bowel Disease (EC-IBD) Group incepted European and Israeli patients prospectively at diagnosis of ulcerative colitis from 1991 to 1993. Patients having more than 5 years unbroken tracking from diagnosis within a 10-year time horizon were grouped into clinical transition states by: (1) medical and surgical therapies recorded in continuous quarter-year cycles, (2) presence of flare-years in a minority (<50%) or majority (>50%) of the follow-up years (hereafter called “minority flare-years” patients or “majority flare-years” patients respectively). Clinical course transition states (graded by treatment) were calculated by a Markov model (SPSS 16, STATA 10.1). The 5 transition states were defined as follows: “remission” (symptomatic treatment), “mild-moderate” (local corticosteroids, budesonide, mesalazine, antibiotics), “severe” (systemic steroids, immunosuppression, biologics), surgery (abdominal and pouch surgery), and death (from ulcerative
S9
colitis). Healthcare costs per patient per cycle were matched to the transition states. Results: 705 patients had 39208 cycles. In 644 cases with minority flare-years, the probability (expressed per cycle) of worsening (to a more severe state or surgery or death) of the “remission state” was 0.0811, of “mild-moderate state” 0.0763, of “severe state” 0.2664. In 61 cases with majority flare-years, the probability of worsening of the “remission state” was 0.2980, of “mild-moderate state” 0.1432, of “severe state” 0.2733. Minority flare-year patients in the initial “surgery state” had probabilities of 0.3291 for subsequent mild disease and 0.3924 for severe disease (pouchitis), and 0.0506 for pouch removal; majority flare-year patients had probabilities 0.3750 for mild or severe disease (pouchitis). The subsequent “surgery state” in the minority flare-years group acquired cases mostly from “surgery” (patients postcolectomy requiring pouch removal, probability 0.0506), and in the majority flare-years group from “severe” disease (patients requiring colectomy, probability 0.0104). Mean healthcare costs (euros/patient-cycle) were as follows: remission 93, mildmoderate 267, severe 939, surgery 8623, death 655. Surgery accounted for 72% of costs in year 1, and 83% in follow-up year 10. Conclusions: Severe ulcerative colitis has an inferior prognosis and high healthcare costs, with surgery accounting for the greatest expense. There is a considerable probability of pouchitis after surgery. Medical treatments must aim therefore to maintain patients in remission and avoid the need for surgical operations. 15 Laparoscopic-assisted versus open ileocolic resection for Crohn’s disease: long term results of a prospective randomized trial E.J. Eshuis1 *, J.F.M. Slors1 , M.A. Cuesta2 , R.E.G. Pierik3 , P.C.F. Stokkers1 , M.A.G. Sprangers1 , W.A. Bemelman1 . 1 Academic Medical Center, Amsterdam, Netherlands, 2 Free University Medical Center, Amsterdam, Netherlands, 3 Isala Clinics, Zwolle, Netherlands Aim: Four meta-analyses exist evaluating the short term results of laparoscopic versus open ileocolic resection for Crohn’s disease. Little is known about the long term results of both procedures with respect to surgical recurrence rate, overall reoperation rate, incidence of incisional hernia, adhesive small bowel obstruction, quality of life (QOL) and Body Image (BI) and cosmesis. The objective of this study is to determine the long term results of a randomized multicenter study comparing laparoscopic with open ileocolic resection for Crohn’s disease. Materials and Methods: Sixty patients who participated in this trial were prospectively followed in the outpatient clinic. Patients had an ileocolic resection between 1999 and 2003. Primary outcome parameters were overall reoperation and readmission rate and re-resection rate for recurrent Crohn’s disease. Secondary outcomes were QOL, BI and cosmesis. Results: Five patients, 1 from the laparoscopic group and 4 from the open group were lost to follow up. The groups were comparable for characteristics as sex, age, and maintenance therapy. Mean follow-up was 6.8 years. Overall, 16/29 (55%) and 16/26 (62%) patients remained relapse-free after the ileocolic resection in the laparoscopic and open group respectively ( p = NS). Resection of recurrent Crohn’s disease occurred in 2/29 (7%) and 3/26 (12%) patients ( p = NS). Two reoperations for incisional hernia were done in the open group (2/26 [8%]) vs. nil in the laparoscopic group. Reoperation for adhesive small bowel obstruction was done twice in the open group (2/26 [8%]) vs. nil in the laparoscopic group. Overall reoperation rate was 2/29 (7%) versus 7/26 (27%)