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P551 Detection of anti infliximab antibodies in patients with inflammatory bowel disease (IBD) in the presence of infliximab by homogeneous liquid phase anti infliximab mobility shift assay
Clinical: Therapy and observation Reference(s) [1] Kopylov U, Mantzaris GJ, Katsanos KH et al, (2011), The efficacy of shortening the dosing interval to once every six weeks in Crohn’s patients losing response to maintenance dose of infliximab. [2] Katz L, Gisbert JP, Manoogian B, et al, (2012), Doubling the infliximab dose versus halving the infusion intervals in Crohn’s disease patients with loss of response. [3] Rostholder E, Ahmed A, Cheifetz AS et al. (2012), Outcomes after escalation of infliximab therapy in ambulatory patients with moderately active ulcerative colitis. P550 Diagnosing and treating pediatric Crohn’s disease patients: is there a difference between adult and pediatric gastroenterologists’ practices? Results of the BELCRO cohort E. De Greef1 *, B. Maus2 , I. Hoffman3 , F. Smets4 , S. Van Biervliet5 , M. Scaillon6 , B. Hauser7 , I. Paquot8 , P. Alliet9 , W. Arts10 , O. Dewit11 , H. Peeters12 , F. Baert13 , G. D’Haens14 , J.-F. Rahier15 , I. Etienne16 , O. Bauraind8 , A. Van Gossum17 , S. Vermeire18 , F. Fontaine19 , V. Muls20 , E. Louis21 , F. Van De Mierop22 , J. Coche23 , J.J. Mahachie2 , K. Van Steen2 , G. Veereman24 . 1 UZ Brussels, Pediatric Gastroenterology, Jette, Belgium, 2 ULG, Montefiore Institute, Liege, Belgium, 3 Uz Gasthuisberg, Pediatric Gastroenterology, Leuven, Belgium, 4 UCL St Luc, Pediatric Gastroenterology, Brussel, Belgium, 5 UZ Gent, Pediatric Gastroenterology, Gent, Belgium, 6 Hˆ opital des enfants Reine Paola, Pediatric Gastroenterology, Brussel, Belgium, 7 UZ Brussels, Pediatric Gastroenterology, Brussel, Belgium, 8 CHC Clinique de l’Esperance, Pediatric Gastroenterology, Liege, Belgium, 9 Jessa Hospital, Pediatric Gastroenterology, Hasselt, Belgium, 10 ZOL, Pediatric Gastroenterology, Genk, Belgium, 11 UCL St Luc, Gastroenterology, Brussel, Belgium, 12 UZ Gent, Gastroenterology, Gent, Belgium, 13 Heilig Hart Hospital, Gastroenterology, Roesselare, Belgium, 14 AMC, Gastroenterology, Amsterdam, Netherlands, 15 UCL Montgodinne, Gastroenterology, Mont Godinne, Belgium, 16 CHR Citadelle, Pediatric Gastroenterology, Liege, Belgium, 17 ULB Erasme, Gastroenterology, Brussel, Belgium, 18 Uz Gasthuisberg, Gastroenterology, Leuven, Belgium, 19 CHU St Joseph, Gastroenterology, Liege, Belgium, 20 ULB St Pierre, Gastroenterology, Brussel, Belgium, 21 ULG, Gastroenterology, Liege, Belgium, 22 AZ St Augustinus, Gastroenterology, Wilrijk, Belgium, 23 Clinique Saint Pierre, Gastroenterology, Ottignies, Belgium, 24 UZ Brussels, Pediatric Gastroenterology, Brussels, Belgium Background: Pediatric gastroenterologists treat Crohn’s disease patients up to 15 18 years of age and then transfer them to adult care. However, there is no restriction for adult colleagues to diagnose and treat pediatric patients. Methods: In the current survey, we investigated differences in presentation, use of diagnostic procedures and initial treatment for pediatric Crohn’s disease patients under the care of pediatric versus adult gastroenterologists. This comparison was made in the cohort of BELCRO patients diagnosed by a pediatric or adult gastroenterologist. Results: In the BELCRO cohort, 71% of patients were diagnosed by a pediatric gastroenterologist of whom 58% in a tertiary care centre compared to 37% of the 29% of patients in adult care. Even though patients diagnosed by adult physicians are significantly older, 22% were below the age of 12 y. No difference in presenting symptoms (abdominal pain, diarrhoea, growth failure) or disease severity at diagnosis was found between both groups. Disease classification according to Montreal [1] and the recently adapted Paris [2] classification was similar. Pediatric gastroenterologists performed as many upper endoscopies at diagnosis before and after publication of the Porto criteria (75%) [3], whereas adult physicians
S231 performed significantly less upper endoscopies. At diagnosis, adult physicians initially prescribed more monotherapy with 5-ASA and were less inclined to use combination therapy with steroids, immunomodulators, antibiotics or enteral nutrition compared to pediatric colleagues. Conclusions: Further follow up will indicate whether differences between pediatric and adult practitioners affect long term disease behaviour and outcome. Reference(s) [1] Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19 Suppl A:5 36 [2] Levine A, Griffiths A, Markowitz J, et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification. IBD. 2011;17:1314 1321 [3] Inflammatory bowel disease in children and adolescents: recommendations for diagnosis–the Porto criteria. J Pediatr Gastroenterol Nutr. 2005;41:1 7 P551 Detection of anti infliximab antibodies in patients with inflammatory bowel disease (IBD) in the presence of infliximab by homogeneous liquid phase anti infliximab mobility shift assay A. Eser1 *, C. Primas1 , S. Haunstein2 , S. Lockton2 , S. Wang2 , S. Singh2 , W. Reinisch1 . 1 Medical University of Vienna, Vienna, Austria, 2 Prometheus Labs Inc, San Diego, United States Background: Trough levels (TL) as well as c-max levels have been positively associated with efficacy and negatively with immunogenicity of infliximab (IFX) in patients with IBD. Degradation of IFX is largely determined by the presence of anti drug antibodies (ADA), increasing its clearance between 1.4- and 2.7-fold. With evidence accumulating in favour of the concept of therapeutic drug monitoring, standard enzyme linked immunosorbent assays (ELISA) for the detection of ADA reach their limits, as the presence of high IFX levels strongly interferes with the detection of ADA. Here we assess the perfomance of a new assay for the detection of ADA at midinfusion timepoints as compared to samples immediately prior to the next IFX infusion. Methods: 90 consecutive patients with established IBD (66 with Crohn’s disease, 24 with Ulcerative Colitis) under maintenance therapy with IFX were asked to participate. Serum samples were acquired at half time between two infusions and immediately prior to the subsequent infusion. IFX drug levels were measured by ELISA (Immundiagnostik, Germany) and ADA were assessed by homogeneous liquid phase anti Infliximab mobility shift assay (HLPA) (Prometheus Labs Inc., CA) for all time points. Results: Patients were receiving a median dose of IFX of 5.51 mg/kg bodyweight (4.08 10.94), yielding a median TL of 8.98 mg/ml IFX. Infliximab serum levels were significantly higher at mid infusion versus TL (p = 0.000). ADA were detectable in 18 patients and 23 patients at mid infusion and trough timepoints, respectively. 16 patients were concordantly positive, 2 were positive at mid infusion and 5 at time of trough sampling. The agreement for the outcome positive ADA measured at week 4 versus week 8 yields a Cohen’s kappa of 0.80, with a correlation of t = 0.651 (p = 0.001). ADA occurred most frequently in patients with non-detectable or very low TL (Table 1). Conclusions: With HLPA, it is feasible to detect ADA against IFX with excellent accordance not only at low levels of circulating infliximab but also earlier within an infusion interval, when IFX concentrations are high and interfering with conventional
S232
Poster presentations
ELISAs. ADAs are preferrentially detected in patients with negative or low TLs. Table 1. Occurrence of anti infliximab antibodies (ADA) in patients grouped in quartiles along IFX trough levels Quartile
IFX serum trough level range (mg/ml)
ADA positivity (% of quartile)
1st 2nd 3rd 4th
0 2.31 2.57 7.57 7.59 14.90 14.98 39.59
17/22 (77%) 4/23 (17%) 2/23 (9%) 0/22 (0%)
P552 Current practice in the diagnosis and management of IBD-associated anemia and iron deficiency in Germany: The German AnemIBD study I. Blumenstein1 , S. Vollmer2 , W. Klemm3 , G. Virgin4 , S. Weber-Mangal4 , J. Stein5 *. 1 Frankfurt University Hospital, Medical Dpt. 1, Frankfurt, Germany, 2 Gastroenterological Practice, G¨ oppingen, Germany, 3 Gastroenterological Practice, Cottbus, Germany, 4 Vifor Pharma Germany, Munich, Germany, 5 Crohn Colitis Zentrum Rhein-Main, Frankfurt, Germany Background: Anemia represents the most common systemic complication in inflammatory bowel disease (IBD). Although the cause of anemia in IBD is multifactorial, iron deficiency (ID) is one of the most prevalent underlying reasons. Recent IBD guidelines suggest that iron supplementation should be preferably administered intravenously, even though some patients may respond to orally administered iron (Gasche et al. IBD; 2007). The results of a non-interventional study (NIS) give insight into the current status of anemia management in German IBD patients. Methods: Up to August 2010, 193 IBD patients (116 Crohn’s disease [CD] and 78 colitis ulcerosa [CU]) were included in the NIS. Mean patient age was 39 years (range: 36 83 yrs.) with 79 (41%) male patients included. Enrolled subjects suffered from IBD and anemia and had received care at their study center for at least 12 months prior study inclusion. Results: 54 office-based gastroenterologists reported 193 cases of IBD-associated anemia. Anemia and iron status were mainly assessed by hemoglobin (Hb; 100%) and serum ferritin (97%). Transferrin saturation (TSAT) was tested in 82% of patients. Mean Hb at diagnosis was 10.1±1.4 g/dL, serum ferritin 51.2±122 mg/L and transferrin saturation (TSAT) 14.0±12.6%. In the 6 months prior to inclusion, only 84 (43.5%) of patients had received anti-anemic treatment. Of those 47 (56%) had received oral iron, 13 (15%) parenteral iron, 16 (19%) oral plus parenteral iron and 8 (10%) transfusions. Erythropoietin stimulating agents had not been given. Conclusions: Although i.v. administration of iron is recommended as the preferred route for iron therapy for IBD patients, current practice in Germany continues to rely on oral iron preparations in most iron-treated patients with IBD, even when severely anemic. Insufficient replacement of iron or monitoring of iron status is indicated by the frequency of severe anemia in this cohort of 193 patients. The proportion of patients with IBD and inadequately or untreated anemia and/or iron deficiency remains to be determined, however greater awareness of the existing guidelines for managing iron deficiency in IBD patients appears necessary.
P553 Coping strategies for worsening conditions and their perceived effectiveness in patients with inflammatory bowel disease M. Tanaka1 *, A. Kawakami1 , Y. Iwao2 , T. Fukushima3 , M. Nishigaki1 , M. Suzuki1 , H. Sanada1 , N. Yamamoto-Mitani1 . 1 The University of Tokyo, School of Health Sciences and Nursing, Tokyo, Japan, 2 Keio University School of Medicine, Center for Preventive Medicine, Tokyo, Japan, 3 Matsushima Clinic, Yokohama, Japan Background: Although self-management is important for patients with inflammatory bowel disease (IBD), there is little research focusing on their coping strategies, especially in worsening conditions. This study aimed to investigate coping strategies of IBD patients for worsening conditions and their perceived effectiveness. Methods: Questionnaires were mailed to 1,641 members of the Crohn’s and Colitis Foundation of Japan. A questionnaire containing 11 types of coping strategies for worsening conditions was developed based on interviews to patients with IBD. We investigated how many used each strategy in a fourpoint Likert-scale, and recoded it into “uses the strategy” or not. Perceived effectiveness of each coping strategy for worsening conditions was asked, by effective or not, to those who answered that he/she used that strategy. The responses were described by disease group. Results: A total of 426 (response rate 26%) questionnaires were returned. Data from 260 UC patients (age mean±SD = 47.2±17.1) and 140 CD patients (41.3±12.5) were used. The strategies used by more than half of both patients were “change contents of meals” (UC: 85.8%, CD: 93.6%), “get more sleep” (UC: 77.3%, CD: 82.1%), “see a doctor immediately without waiting for the next appointment” (UC: 73.1%, CD: 67.1%), and “take a day off” (UC: 57.7%, CD: 65.7%). In addition, “skip some meals” (81.4%), and “take/add elemental diet” (63.6%) were characteristically used by CD patients. “Use extra topical corticosteroids” were used by 21.5% of UC patients. Among subjects who used a strategy, strategies with high percentages of perceived effectiveness were “use extra topical corticosteroids” (53.6%) for UC, while “skip some meals” (61.4%) and “take/add elemental diet” (59.6%) were used by CD patients. As many as 35.4% of patients with UC and 20.7% of CD answered “there is no effective coping strategy”. Conclusions: The additional use of topical medication and elemental diet were regarded as the most effective selftreatment. However, the number of patients who used these treatments was relatively small from those who merely modified their lifestyle. The effectiveness of the additional use of topical medication for UC patients and elemental diet for CD patients should be emphasized in patient education for selfmanagement. Financial Disclosure: This work was supported by a Grant-in-Aid for Young Scientists (B) (22792175), Tokyo, Japan. P554 Conventional electrochemiluminescence immunoassay method underestimates cortisol suppression in patients with ulcerative colitis treated with oral prednisone F. Manguso1 *, R. Bennato1 , G. Lombardi1 , A. Viola2 , E. Riccio1 . 1 AORN A. Cardarelli, UOC Gastroenterology, Napoli, Italy, 2 AORN A. Cardarelli, Hematology and Stem Cell Transplantation, Napoli, Italy Background: In samples from patients who have been treated with prednisone (PD) concentrations of cortisol may be overestimated by using conventional electrochemiluminescence immunoassay (ECLIA) method. The aim of the study was the quantification of blood cortisol levels by using ECLIA compared to a selective liquid chromatography-tandem mass
S231 performed significantly less upper endoscopies. At diagnosis, adult physicians initially prescribed more monotherapy with 5-ASA and were less inclined to use combination therapy with steroids, immunomodulators, antibiotics or enteral nutrition compared to pediatric colleagues. Conclusions: Further follow up will indicate whether differences between pediatric and adult practitioners affect long term disease behaviour and outcome. Reference(s) [1] Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19 Suppl A:5 36 [2] Levine A, Griffiths A, Markowitz J, et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification. IBD. 2011;17:1314 1321 [3] Inflammatory bowel disease in children and adolescents: recommendations for diagnosis–the Porto criteria. J Pediatr Gastroenterol Nutr. 2005;41:1 7 P551 Detection of anti infliximab antibodies in patients with inflammatory bowel disease (IBD) in the presence of infliximab by homogeneous liquid phase anti infliximab mobility shift assay A. Eser1 *, C. Primas1 , S. Haunstein2 , S. Lockton2 , S. Wang2 , S. Singh2 , W. Reinisch1 . 1 Medical University of Vienna, Vienna, Austria, 2 Prometheus Labs Inc, San Diego, United States Background: Trough levels (TL) as well as c-max levels have been positively associated with efficacy and negatively with immunogenicity of infliximab (IFX) in patients with IBD. Degradation of IFX is largely determined by the presence of anti drug antibodies (ADA), increasing its clearance between 1.4- and 2.7-fold. With evidence accumulating in favour of the concept of therapeutic drug monitoring, standard enzyme linked immunosorbent assays (ELISA) for the detection of ADA reach their limits, as the presence of high IFX levels strongly interferes with the detection of ADA. Here we assess the perfomance of a new assay for the detection of ADA at midinfusion timepoints as compared to samples immediately prior to the next IFX infusion. Methods: 90 consecutive patients with established IBD (66 with Crohn’s disease, 24 with Ulcerative Colitis) under maintenance therapy with IFX were asked to participate. Serum samples were acquired at half time between two infusions and immediately prior to the subsequent infusion. IFX drug levels were measured by ELISA (Immundiagnostik, Germany) and ADA were assessed by homogeneous liquid phase anti Infliximab mobility shift assay (HLPA) (Prometheus Labs Inc., CA) for all time points. Results: Patients were receiving a median dose of IFX of 5.51 mg/kg bodyweight (4.08 10.94), yielding a median TL of 8.98 mg/ml IFX. Infliximab serum levels were significantly higher at mid infusion versus TL (p = 0.000). ADA were detectable in 18 patients and 23 patients at mid infusion and trough timepoints, respectively. 16 patients were concordantly positive, 2 were positive at mid infusion and 5 at time of trough sampling. The agreement for the outcome positive ADA measured at week 4 versus week 8 yields a Cohen’s kappa of 0.80, with a correlation of t = 0.651 (p = 0.001). ADA occurred most frequently in patients with non-detectable or very low TL (Table 1). Conclusions: With HLPA, it is feasible to detect ADA against IFX with excellent accordance not only at low levels of circulating infliximab but also earlier within an infusion interval, when IFX concentrations are high and interfering with conventional
S232
Poster presentations
ELISAs. ADAs are preferrentially detected in patients with negative or low TLs. Table 1. Occurrence of anti infliximab antibodies (ADA) in patients grouped in quartiles along IFX trough levels Quartile
IFX serum trough level range (mg/ml)
ADA positivity (% of quartile)
1st 2nd 3rd 4th
0 2.31 2.57 7.57 7.59 14.90 14.98 39.59
17/22 (77%) 4/23 (17%) 2/23 (9%) 0/22 (0%)
P552 Current practice in the diagnosis and management of IBD-associated anemia and iron deficiency in Germany: The German AnemIBD study I. Blumenstein1 , S. Vollmer2 , W. Klemm3 , G. Virgin4 , S. Weber-Mangal4 , J. Stein5 *. 1 Frankfurt University Hospital, Medical Dpt. 1, Frankfurt, Germany, 2 Gastroenterological Practice, G¨ oppingen, Germany, 3 Gastroenterological Practice, Cottbus, Germany, 4 Vifor Pharma Germany, Munich, Germany, 5 Crohn Colitis Zentrum Rhein-Main, Frankfurt, Germany Background: Anemia represents the most common systemic complication in inflammatory bowel disease (IBD). Although the cause of anemia in IBD is multifactorial, iron deficiency (ID) is one of the most prevalent underlying reasons. Recent IBD guidelines suggest that iron supplementation should be preferably administered intravenously, even though some patients may respond to orally administered iron (Gasche et al. IBD; 2007). The results of a non-interventional study (NIS) give insight into the current status of anemia management in German IBD patients. Methods: Up to August 2010, 193 IBD patients (116 Crohn’s disease [CD] and 78 colitis ulcerosa [CU]) were included in the NIS. Mean patient age was 39 years (range: 36 83 yrs.) with 79 (41%) male patients included. Enrolled subjects suffered from IBD and anemia and had received care at their study center for at least 12 months prior study inclusion. Results: 54 office-based gastroenterologists reported 193 cases of IBD-associated anemia. Anemia and iron status were mainly assessed by hemoglobin (Hb; 100%) and serum ferritin (97%). Transferrin saturation (TSAT) was tested in 82% of patients. Mean Hb at diagnosis was 10.1±1.4 g/dL, serum ferritin 51.2±122 mg/L and transferrin saturation (TSAT) 14.0±12.6%. In the 6 months prior to inclusion, only 84 (43.5%) of patients had received anti-anemic treatment. Of those 47 (56%) had received oral iron, 13 (15%) parenteral iron, 16 (19%) oral plus parenteral iron and 8 (10%) transfusions. Erythropoietin stimulating agents had not been given. Conclusions: Although i.v. administration of iron is recommended as the preferred route for iron therapy for IBD patients, current practice in Germany continues to rely on oral iron preparations in most iron-treated patients with IBD, even when severely anemic. Insufficient replacement of iron or monitoring of iron status is indicated by the frequency of severe anemia in this cohort of 193 patients. The proportion of patients with IBD and inadequately or untreated anemia and/or iron deficiency remains to be determined, however greater awareness of the existing guidelines for managing iron deficiency in IBD patients appears necessary.
P553 Coping strategies for worsening conditions and their perceived effectiveness in patients with inflammatory bowel disease M. Tanaka1 *, A. Kawakami1 , Y. Iwao2 , T. Fukushima3 , M. Nishigaki1 , M. Suzuki1 , H. Sanada1 , N. Yamamoto-Mitani1 . 1 The University of Tokyo, School of Health Sciences and Nursing, Tokyo, Japan, 2 Keio University School of Medicine, Center for Preventive Medicine, Tokyo, Japan, 3 Matsushima Clinic, Yokohama, Japan Background: Although self-management is important for patients with inflammatory bowel disease (IBD), there is little research focusing on their coping strategies, especially in worsening conditions. This study aimed to investigate coping strategies of IBD patients for worsening conditions and their perceived effectiveness. Methods: Questionnaires were mailed to 1,641 members of the Crohn’s and Colitis Foundation of Japan. A questionnaire containing 11 types of coping strategies for worsening conditions was developed based on interviews to patients with IBD. We investigated how many used each strategy in a fourpoint Likert-scale, and recoded it into “uses the strategy” or not. Perceived effectiveness of each coping strategy for worsening conditions was asked, by effective or not, to those who answered that he/she used that strategy. The responses were described by disease group. Results: A total of 426 (response rate 26%) questionnaires were returned. Data from 260 UC patients (age mean±SD = 47.2±17.1) and 140 CD patients (41.3±12.5) were used. The strategies used by more than half of both patients were “change contents of meals” (UC: 85.8%, CD: 93.6%), “get more sleep” (UC: 77.3%, CD: 82.1%), “see a doctor immediately without waiting for the next appointment” (UC: 73.1%, CD: 67.1%), and “take a day off” (UC: 57.7%, CD: 65.7%). In addition, “skip some meals” (81.4%), and “take/add elemental diet” (63.6%) were characteristically used by CD patients. “Use extra topical corticosteroids” were used by 21.5% of UC patients. Among subjects who used a strategy, strategies with high percentages of perceived effectiveness were “use extra topical corticosteroids” (53.6%) for UC, while “skip some meals” (61.4%) and “take/add elemental diet” (59.6%) were used by CD patients. As many as 35.4% of patients with UC and 20.7% of CD answered “there is no effective coping strategy”. Conclusions: The additional use of topical medication and elemental diet were regarded as the most effective selftreatment. However, the number of patients who used these treatments was relatively small from those who merely modified their lifestyle. The effectiveness of the additional use of topical medication for UC patients and elemental diet for CD patients should be emphasized in patient education for selfmanagement. Financial Disclosure: This work was supported by a Grant-in-Aid for Young Scientists (B) (22792175), Tokyo, Japan. P554 Conventional electrochemiluminescence immunoassay method underestimates cortisol suppression in patients with ulcerative colitis treated with oral prednisone F. Manguso1 *, R. Bennato1 , G. Lombardi1 , A. Viola2 , E. Riccio1 . 1 AORN A. Cardarelli, UOC Gastroenterology, Napoli, Italy, 2 AORN A. Cardarelli, Hematology and Stem Cell Transplantation, Napoli, Italy Background: In samples from patients who have been treated with prednisone (PD) concentrations of cortisol may be overestimated by using conventional electrochemiluminescence immunoassay (ECLIA) method. The aim of the study was the quantification of blood cortisol levels by using ECLIA compared to a selective liquid chromatography-tandem mass