- Email: [email protected]
P288 Therapeutic efficacy of granulocytapheresis in inflammatory bowel diseases: A prospective observational study
S124 Methods: An online survey was conducted of patients with a CD diagnosis for at least 1 year and a conjoint analysis was performed to evaluate patient preference over different CD health states. Participants were asked to make preference choices between CD health states and EQ-5D health states (defined by EQ-5D item response combinations). Definitions of the CD health states were provided to help patients familiarise with the concepts. Patients were asked to make the preference choice between the randomly selected CD health state and the comparative EQ-5D health states. The selection of the subsequent EQ-5D comparators depended on the prior choices to ensure efficient estimation. Based on the data collected, logistic regression was run for each CD health state separately to estimate the probability of preferring the CD health state over various utility levels defined by EQ-5D health states. The utility value of a CD health state was defined as the probability of over 70% preference on that CD health state. A sensitivity analysis was conducted where the current survey respondents were standardised based on the age and gender distributions from the patients with CD from the 2008 Medical Expenditure Panel Survey. Results: A total of 124 patients completed the survey. About half of the participants (before/after weighting) were female (50.8%/62.4%) with a mean (±standard deviation) age of 52.27±11.91/45.5±15.8). The majority of the participants self-reported in remission or mild disease (80.6%/85.1%) and half of them had surgical resection (51.6%/48.6%). Although nearly three quarters (72.6%/74.7%) were on prescription treatment for CD, less than half (43.5%/44.2%) experienced active symptoms in the past 4 weeks. The estimated utility values for the 5 CD health states (ie, deep remission, CR without MH, MH without CR, moderate CD, and severe CD) were 0.949, 0.767, 0.766, 0.370, and 0.019, respectively, demonstrating a higher utility score for a better/preferred health state. Similar estimates were obtained in sensitivity analysis. Conclusions: Deep remission was clearly preferred over clinical remission only and mucosal healing only. Moderate CD and severe CD were much less preferred, with severe CD having the lowest estimated utility score. P287 Adverse effects of medication in IBD: A single center prospective observational study ujo1 , R. Ramalho1 , J. Machado1 *, P. Ministro1 , R. Ara´ E. Cancela1 , A. Castanheira1 , A. Silva1 . 1 S. Teot´ onio Hospital, Gastroenterology, Viseu, Portugal Background: Inflammatory Bowel Disease (IBD) encompasses three chronic clinical entities, Crohn Disease (CD), Ulcerative Colitis (UC) and Unclassified Colitis (UNCC). The aetiology is unknown and therefore a causal therapy is not available. Different therapeutic approaches may be considered during follow-up taking into account disease activity, location and behaviour. Drugs approved to treat IBD have distinct potencies but also have different safety profiles. The aim of this study was to characterize adverse effects (AE) associated to drugs used in a population of patients with IBD during 36 months. Methods: A prospective observational study of drug adverse effects in a population with IBD was conducted. Patients with IBD diagnosis (CD, UC or UNCC) of a tertiary medical center treated with Mesalazine (5-ASA), Azathioprine (AZA), Methotrexate (MTX), Infliximab (INF) or Adalimumab (ADA) were included. Data were systematically registered using a predefined form. SPSS 17.0 was used for statistical analysis. Results: A total of 244 patients were included. The mean age was 44.5±2.3 years. Fifty-three percent (n = 130) were female and 47% (n = 114) were male. Fifty-two percent (n = 127) had UC, 44.7% (n = 109) had CD and 3% (n = 8) had UNCC.
Poster presentations Mean follow-up was 1031±153 days. Adverse effects were registered in 17.6% (n = 43) of the patients and 14% (n = 6) of those developed side effects to two or more drugs. A total of 50 adverse effects were registered, 56% (n = 28) of those resulted in temporary disability and 38% (n = 19) were considered serious adverse events (SAE). Fifteen patients were admitted as inpatient. No fatal events were registered. Adverse effects to each drug are registered in table 1. Table 1 No. of patients treated AE SAE
Mesalazine
Azathioprine
Methotrexate
Infliximab
Adalimumab
242 7% (n = 17) 1.7% (n = 4)
82 26.8% (n = 22) 7.3% (n = 6)
5 20% (n = 1) 0% (n = 0)
25 28% (n = 7) 24% (n = 6)
6 33.3% (n = 2) 33.3% (n = 2)
Conclusions: As we expected patients treated with classical imunnosuppressive agents and biological therapies had more adverse effects than those treated with mesalazine. Adverse effects related to biological therapies were more severe than those related to classical imunnosuppressive agents. P288 Therapeutic efficacy of granulocytapheresis in inflammatory bowel diseases: A prospective observational study R. Sacco1 *, A. Romano1 , M. Bertini1 , M. Bertoni1 , G. Federici1 , A. Mazzoni1 , S. Metrangolo1 , G. Parisi1 , A. Scaramuzzino1 , E. Tumino1 , F. Scatena1 , G. Bresci2 . 1 Pisa University Hospital, Pisa, Italy, 2 Pisa University Hospital, Divisione di Gastroenterologia e Malattie del Ricambio, Pisa, Italy Background: Inflammatory bowel diseases (IBDs) are chronic relapsing conditions. The optimal therapeutic approach to achieve remission is still unclear. We report here our prospective observational experience in the use of granulocytapheresis for the treatment of these conditions and the achievement of long-term remission. Methods: In total, 70 IBD patients who did not respond to treatment with corticosteroids and mesalamine for four weeks were enrolled in this prospective observational study. Forty patients had total active ulcerative colitis (UC) and 30 presented active Crohn’s disease (CD) (16 with ileal location and 14 with ileocolonic location). All patients were treated with granulocytapheresis, using the AdacolumnTM system, an adsorption column which selectively binds granulocytes and monocytes, for one session/week for 5 consecutive weeks. Steroid treatment was not permitted. Disease activity was evaluated by clinical disease index (CAI) in patient with UC and by Crohn’s Disease Activity Index (CDAI) in those with CD: a clinical remission was defined as CAI <6 or CDAI <150. All patients were followed for more than 12 months after the end of granulocytapheresis. The endoscopic index (EI) was also evaluated. Results: All patients completed the study; no complications were reported. After the end of granulocytapheresis, 47/70 (67%) patients showed a clinical remission: 28/40 (70%) of those with UC and 19/30 (63%) of CD subjects. At 6 months after the granulocytapheresis, clinical remission of disease was still observed in 24/40 (60%) UC patients and 16/30 (53%) CD patients; at 12 months, disease remission was reported in 16/40 (40%) UC subjects and 12/30 (43%) CD subjects. The values of CAI, EI, and CDAI before and after the granulocytapheresis are reported in the table.
UC CD
CAI before
after
EI before
after
CDAI before
after
8 -
2 -
12 12
5 8
190
150
Clinical: Therapy and observation Conclusions: On the basis of this observational experience, granulocytapheresis appears effective and well tolerated for the treatment of IBD patients. These preliminary findings may suggest the conduction of further randomized multicenter trials, in order to shed new lights on the use of granulocytapheresis for the treatment of IBD. P289 Concordance in IBD endoscopic scoring requires expertise and training: Preliminary results of an ongoing IG-IBD study M. Daperno1 *, M. Comberlato2 , F. Bossa3 , L. Biancone4 , A. Bonanomi5 , A. Cassinotti6 , R. Cosintino7 , G. Lombardi8 , R. Mangiarotti7 , A. Orlando9 , A. Papa10 , R. Pica11 , F. Rizzello12 , R. D’Inc` a13 , on behalf of Italian Group for Inflammatory Bowel Disease (IG-IBD). 1 A.O. Ordine Mauriziano, Gastroenterology Unit, Turin, Italy, 2 Ospedale di Bolzano, Gastroenterology Unit, Bolzano, Italy, 3 IRCCS Ospedale Casa Sollievo della Sofferenza, Gastroenterology Unit, San Giovanni Rotondo, Italy, 4 A.O. Universitaria Policlinico Tor Vergata Roma, Gastroenterology Unit, Rome, Italy, 5 A.O.U. Careggi, Gastroenterology Unit, Florence, Italy, 6 L. Sacco University Hospital, Department of Gastroenterology, Milan, Italy, 7 San Camillo Forlanini Hospitals, Rome, Italy, 8 A.O. Cardarelli, Gastroenterology Unit, Naples, Italy, 9 V Cervello Hospital, Istituto di Medicina Generale e Pneumologia Reparto di Medicina Interna, Palermo, Italy, 10 Catholic University of Rome, Internal Medicine and Gastroenterology Complesso Integrato Columbus, Rome, Italy, 11 Universit` a La Sapienza, Gastroenterology Unit, Rome, Italy, 12 Policlinico S. Orsola Malpigli-Universit` a Di Bologna, Di Medicina Interna e Gastroenterologia, Bologna, Italy, 13 University of Padua, Padua, Italy Background: Endoscopic scoring is an essential tool required for clinical trials and probably for routine practice. As multicenter studies increasingly include endoscopic evaluation as relevant end-point, reliability of endoscopic scoring may become an issue. Aim of this multicenter IG-IBD study was to explore reproducibility of endoscopic scoring in the setting of dedicated IBD endoscopist, and to evaluate the effectiveness of a dedicated training program in amelioration of basal agreement. Methods: 13 expert endoscopists reviewed endoscopic videoclips (6 ulcerative colitis clips, 5 post-surgical Crohn clips and 5 luminal Crohn clips), and blindly assigned endoscopic scores: Mayo endoscopic subscore for ulcerative colitis Rutgeerts’ score for post-surgical Crohn’s disease CDEIS and SES-CD for luminal Crohn’s disease. At the end of every score assessment, discussion was allowed and reference score was voted unanimously for every clip. The study is still ongoing with a validation phase and an educational program will start early in 2012. Results: 78 combinations were available for every score (based on 13 observers’ scores). Median kappa values were normally distributed (p = 0.1962 and p = 0.0672 for Mayo and Rutgeerts’score, respectively). Median Kappa values for Mayo scores and for Rutgeerts’ score were rather unsatisfactory: 0.4405 (95%CI 0.3750 0.5026) and 0.3750 (95%CI 0.2860 0.4440) respectively. Intraclass correlation coefficients for total CDEIS and SES-CD attributed and computed by the same 13 observers were on the opposite highly significant and reached excellence: 0.8349 (95%CI 0.5414 0.9951) and 0.9287 (95%CI 0.7572 0.9981), respectively. A second meeting is planned and scores will be re-attributed in a blinded fashion, educational material for increasing endoscopic scoring concordance will be produced at the end of the standardization process. Conclusions: Endoscopic scoring is relevant for clinical trials, and the use of scores in clinical practice was advocated in order to better identify relevant changes in endoscopic disease
S125 activity. In this preliminary experience, simpler endoscopic scores (Mayo and Rutgeerts’ score) seem to require a larger amount of education in order to reach adequate agreement, while for more detailed and complex scores (CDEIS and SES-CD) agreement inbetween observers is very high. Reproducibility of endoscopic scores cannot be assumed to be very high, and educational programs aimed to maximize agreement in scoring are mandatory. P290 Infliximab drug levels in Crohn’s disease responding to the treatment J. Morgenstern1 *, E. Baestlein2 , L. Leifeld1 , P. Nguyen3 , J. Stein4 , W. Kruis1 . 1 ev. KH K¨ oln Kalk, Cologne, Germany, 2 Gastroenterologische Gemeinschaftspraxis, Cologne, Germany, 3 Florence-Nightingale-KH, Duesseldorf, Germany, 4 St. Marienkrankenhaus, Frankfurt, Germany Background: Though many studies have investigated antibody formation against Infliximab (IFX) demonstrating poor association to therapeutic effects less, is known about IFX serum levels in successfully treated patients with Crohn’s disease (CD). Methods: Consecutive patients (n = 22) with CD under a scheduled (infusions every 8 weeks) treatment with IFX (5 mg/kg body weight) were recruited. Inclusion criterion was known clinical response to IFX. During the 8 weeks treatment interval IFX serum levels, CRP and Harvey BradshawIndex (HBI) were repeatedly determined. IFX serum levels were measured by using an immuno-competitive assay (Immundiagnostik AG, Bensheim, Germany). Results: Serum levels of IFX between before and one week after infusion showed a dramatic increase (13.13±9.87 mg/ml trough level and 101.62±47.54 mg/ml one week later; mean ±SD). Despite all patients were clinical responders the range of IFX peak levels varied widely (27.6 201 mg/ml). As figure 1 depicts there exists an apparent association between courses of IFX drug levels, CRP and HBI. Mean CRP levels increased beyond 5 mg/l between week 5 and 6 while HBI increased during the same time from 3 to 4. In contrast, at week 4 mean serum levels of IFX decreased below 31 mg/ml, which may be a critical serum level for the clinical response.
Figure 1. Conclusions: IFX serum levels in clinically responding patients with CD increase after IFX infusions significantly but show high interindividual variance in peak concentrations and decay. There is apparent association between the drop of serum IFX levels and increase of CRP, and HBI, where a level of 31 mg/ml may be critical. Worsening of clinical symptoms and CRP is associated to ineffective IFX serum levels and should lead to an adaption of the individual IFX treatment. Measurements of infliximab drug levels were sponsored by Immundiagnostik AG, Bensheim, Germany.
Poster presentations Mean follow-up was 1031±153 days. Adverse effects were registered in 17.6% (n = 43) of the patients and 14% (n = 6) of those developed side effects to two or more drugs. A total of 50 adverse effects were registered, 56% (n = 28) of those resulted in temporary disability and 38% (n = 19) were considered serious adverse events (SAE). Fifteen patients were admitted as inpatient. No fatal events were registered. Adverse effects to each drug are registered in table 1. Table 1 No. of patients treated AE SAE
Mesalazine
Azathioprine
Methotrexate
Infliximab
Adalimumab
242 7% (n = 17) 1.7% (n = 4)
82 26.8% (n = 22) 7.3% (n = 6)
5 20% (n = 1) 0% (n = 0)
25 28% (n = 7) 24% (n = 6)
6 33.3% (n = 2) 33.3% (n = 2)
Conclusions: As we expected patients treated with classical imunnosuppressive agents and biological therapies had more adverse effects than those treated with mesalazine. Adverse effects related to biological therapies were more severe than those related to classical imunnosuppressive agents. P288 Therapeutic efficacy of granulocytapheresis in inflammatory bowel diseases: A prospective observational study R. Sacco1 *, A. Romano1 , M. Bertini1 , M. Bertoni1 , G. Federici1 , A. Mazzoni1 , S. Metrangolo1 , G. Parisi1 , A. Scaramuzzino1 , E. Tumino1 , F. Scatena1 , G. Bresci2 . 1 Pisa University Hospital, Pisa, Italy, 2 Pisa University Hospital, Divisione di Gastroenterologia e Malattie del Ricambio, Pisa, Italy Background: Inflammatory bowel diseases (IBDs) are chronic relapsing conditions. The optimal therapeutic approach to achieve remission is still unclear. We report here our prospective observational experience in the use of granulocytapheresis for the treatment of these conditions and the achievement of long-term remission. Methods: In total, 70 IBD patients who did not respond to treatment with corticosteroids and mesalamine for four weeks were enrolled in this prospective observational study. Forty patients had total active ulcerative colitis (UC) and 30 presented active Crohn’s disease (CD) (16 with ileal location and 14 with ileocolonic location). All patients were treated with granulocytapheresis, using the AdacolumnTM system, an adsorption column which selectively binds granulocytes and monocytes, for one session/week for 5 consecutive weeks. Steroid treatment was not permitted. Disease activity was evaluated by clinical disease index (CAI) in patient with UC and by Crohn’s Disease Activity Index (CDAI) in those with CD: a clinical remission was defined as CAI <6 or CDAI <150. All patients were followed for more than 12 months after the end of granulocytapheresis. The endoscopic index (EI) was also evaluated. Results: All patients completed the study; no complications were reported. After the end of granulocytapheresis, 47/70 (67%) patients showed a clinical remission: 28/40 (70%) of those with UC and 19/30 (63%) of CD subjects. At 6 months after the granulocytapheresis, clinical remission of disease was still observed in 24/40 (60%) UC patients and 16/30 (53%) CD patients; at 12 months, disease remission was reported in 16/40 (40%) UC subjects and 12/30 (43%) CD subjects. The values of CAI, EI, and CDAI before and after the granulocytapheresis are reported in the table.
UC CD
CAI before
after
EI before
after
CDAI before
after
8 -
2 -
12 12
5 8
190
150
Clinical: Therapy and observation Conclusions: On the basis of this observational experience, granulocytapheresis appears effective and well tolerated for the treatment of IBD patients. These preliminary findings may suggest the conduction of further randomized multicenter trials, in order to shed new lights on the use of granulocytapheresis for the treatment of IBD. P289 Concordance in IBD endoscopic scoring requires expertise and training: Preliminary results of an ongoing IG-IBD study M. Daperno1 *, M. Comberlato2 , F. Bossa3 , L. Biancone4 , A. Bonanomi5 , A. Cassinotti6 , R. Cosintino7 , G. Lombardi8 , R. Mangiarotti7 , A. Orlando9 , A. Papa10 , R. Pica11 , F. Rizzello12 , R. D’Inc` a13 , on behalf of Italian Group for Inflammatory Bowel Disease (IG-IBD). 1 A.O. Ordine Mauriziano, Gastroenterology Unit, Turin, Italy, 2 Ospedale di Bolzano, Gastroenterology Unit, Bolzano, Italy, 3 IRCCS Ospedale Casa Sollievo della Sofferenza, Gastroenterology Unit, San Giovanni Rotondo, Italy, 4 A.O. Universitaria Policlinico Tor Vergata Roma, Gastroenterology Unit, Rome, Italy, 5 A.O.U. Careggi, Gastroenterology Unit, Florence, Italy, 6 L. Sacco University Hospital, Department of Gastroenterology, Milan, Italy, 7 San Camillo Forlanini Hospitals, Rome, Italy, 8 A.O. Cardarelli, Gastroenterology Unit, Naples, Italy, 9 V Cervello Hospital, Istituto di Medicina Generale e Pneumologia Reparto di Medicina Interna, Palermo, Italy, 10 Catholic University of Rome, Internal Medicine and Gastroenterology Complesso Integrato Columbus, Rome, Italy, 11 Universit` a La Sapienza, Gastroenterology Unit, Rome, Italy, 12 Policlinico S. Orsola Malpigli-Universit` a Di Bologna, Di Medicina Interna e Gastroenterologia, Bologna, Italy, 13 University of Padua, Padua, Italy Background: Endoscopic scoring is an essential tool required for clinical trials and probably for routine practice. As multicenter studies increasingly include endoscopic evaluation as relevant end-point, reliability of endoscopic scoring may become an issue. Aim of this multicenter IG-IBD study was to explore reproducibility of endoscopic scoring in the setting of dedicated IBD endoscopist, and to evaluate the effectiveness of a dedicated training program in amelioration of basal agreement. Methods: 13 expert endoscopists reviewed endoscopic videoclips (6 ulcerative colitis clips, 5 post-surgical Crohn clips and 5 luminal Crohn clips), and blindly assigned endoscopic scores: Mayo endoscopic subscore for ulcerative colitis Rutgeerts’ score for post-surgical Crohn’s disease CDEIS and SES-CD for luminal Crohn’s disease. At the end of every score assessment, discussion was allowed and reference score was voted unanimously for every clip. The study is still ongoing with a validation phase and an educational program will start early in 2012. Results: 78 combinations were available for every score (based on 13 observers’ scores). Median kappa values were normally distributed (p = 0.1962 and p = 0.0672 for Mayo and Rutgeerts’score, respectively). Median Kappa values for Mayo scores and for Rutgeerts’ score were rather unsatisfactory: 0.4405 (95%CI 0.3750 0.5026) and 0.3750 (95%CI 0.2860 0.4440) respectively. Intraclass correlation coefficients for total CDEIS and SES-CD attributed and computed by the same 13 observers were on the opposite highly significant and reached excellence: 0.8349 (95%CI 0.5414 0.9951) and 0.9287 (95%CI 0.7572 0.9981), respectively. A second meeting is planned and scores will be re-attributed in a blinded fashion, educational material for increasing endoscopic scoring concordance will be produced at the end of the standardization process. Conclusions: Endoscopic scoring is relevant for clinical trials, and the use of scores in clinical practice was advocated in order to better identify relevant changes in endoscopic disease
S125 activity. In this preliminary experience, simpler endoscopic scores (Mayo and Rutgeerts’ score) seem to require a larger amount of education in order to reach adequate agreement, while for more detailed and complex scores (CDEIS and SES-CD) agreement inbetween observers is very high. Reproducibility of endoscopic scores cannot be assumed to be very high, and educational programs aimed to maximize agreement in scoring are mandatory. P290 Infliximab drug levels in Crohn’s disease responding to the treatment J. Morgenstern1 *, E. Baestlein2 , L. Leifeld1 , P. Nguyen3 , J. Stein4 , W. Kruis1 . 1 ev. KH K¨ oln Kalk, Cologne, Germany, 2 Gastroenterologische Gemeinschaftspraxis, Cologne, Germany, 3 Florence-Nightingale-KH, Duesseldorf, Germany, 4 St. Marienkrankenhaus, Frankfurt, Germany Background: Though many studies have investigated antibody formation against Infliximab (IFX) demonstrating poor association to therapeutic effects less, is known about IFX serum levels in successfully treated patients with Crohn’s disease (CD). Methods: Consecutive patients (n = 22) with CD under a scheduled (infusions every 8 weeks) treatment with IFX (5 mg/kg body weight) were recruited. Inclusion criterion was known clinical response to IFX. During the 8 weeks treatment interval IFX serum levels, CRP and Harvey BradshawIndex (HBI) were repeatedly determined. IFX serum levels were measured by using an immuno-competitive assay (Immundiagnostik AG, Bensheim, Germany). Results: Serum levels of IFX between before and one week after infusion showed a dramatic increase (13.13±9.87 mg/ml trough level and 101.62±47.54 mg/ml one week later; mean ±SD). Despite all patients were clinical responders the range of IFX peak levels varied widely (27.6 201 mg/ml). As figure 1 depicts there exists an apparent association between courses of IFX drug levels, CRP and HBI. Mean CRP levels increased beyond 5 mg/l between week 5 and 6 while HBI increased during the same time from 3 to 4. In contrast, at week 4 mean serum levels of IFX decreased below 31 mg/ml, which may be a critical serum level for the clinical response.
Figure 1. Conclusions: IFX serum levels in clinically responding patients with CD increase after IFX infusions significantly but show high interindividual variance in peak concentrations and decay. There is apparent association between the drop of serum IFX levels and increase of CRP, and HBI, where a level of 31 mg/ml may be critical. Worsening of clinical symptoms and CRP is associated to ineffective IFX serum levels and should lead to an adaption of the individual IFX treatment. Measurements of infliximab drug levels were sponsored by Immundiagnostik AG, Bensheim, Germany.