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Tu1201 Large Variation in Infliximab Trough Levels Is Associated With Disease Activity in Paediatric Inflammatory Bowel Disease
AGA Abstracts
speculate that steroids may interfere with the mucosal healing induced by polymeric diet reducing it and predisposing patients to earlier relapse of CD. Clinical characteristics by remission induction therapy
CT: corticosteroids; EEN: exclusive enteral nutrition *weeks ¥ at 8 weeks from start Tu1201 Large Variation in Infliximab Trough Levels Is Associated With Disease Activity in Paediatric Inflammatory Bowel Disease Daniël R. Hoekman, Johannan F. Brandse, Tim de Meij, Thalia Hummel, M. Lowenberg, Marc A. Benninga, Geert R. D'Haens, Angelika Kindermann Background: Low serum trough levels (TL) of infliximab (IFX) and the formation of antibodies to IFX (ATI) are associated with the loss of therapeutic response in adults with inflammatory bowel disease (IBD). Up until now, paediatric data are scarce. Therefore, we aimed to investigate the association between ATI and IFX TLs, and clinical and biochemical disease activity in children receiving maintenance treatment with IFX for IBD. Methods: All children aged <18 years receiving scheduled IFX maintenance treatment for Crohn's disease (CD) or ulcerative colitis (UC) in 3 tertiary hospitals in the Netherlands where asked to participate. Prior to two consecutive IFX infusions, IFX TL and ATI were measured. Therapeutic range of IFX was considered 3-7 μg/mL. Furthermore, biochemical disease activity was assessed by C-reactive protein (CRP) and faecal calprotectin (FC) (Bühlman ELISA). Clinical disease activity was determined by activity indices PCDAI and PUCAI, for CD and UC, respectively. Clinical remission was defined as a score of <10 for both PCDAI and PUCAI. A score of >30 or ≥65 was considered severe disease activity for PCDAI and PUCAI, respectively. Results: Between December 2012 and February 2013, thirty-three patients were included (26 CD, 7 UC), with a median age of 14 years [IQR 12-16]. All TL measurements combined (n=66), the median IFX TL was 3.0 μg/mL [IQR 1-6]. Subtherapeutic, therapeutic and supratherapeutic TLs were found in 42.4%, 39.4% and 18.2% of measurements, respectively. ATI were detected in 3 patients but our assay does not allow antibody detection in the presence of drug. Median FC and CRP was 394.5 μg/g and 2.4 mg/L, respectively. At both time points, the majority of patients were either in clinical remission (56.9%) or had mild to moderate clinical disease activity (41.2%). At the first measurement, no significant correlation between IFX TL and clinical or biochemical disease activity was found, although a trend was observed for FC (r=-0.33, p=0.08) and CRP (r=-0.331, p=0.06). At the second measurement, a significant correlation was found between IFX TL and clinical disease activity grading (r=-0.48, p=0.01) and FC (r=-0.49, p=0.01). Patients with therapeutic IFX TLs (≥3 μg/mL) were more likely to be in clinical remission (p=0.01). At both measurements, a significant correlation between clinical disease activity and FC was observed (r=0.53, p<0.01; r=0.50, p=0.02), whereas no correlation was found between CRP and clinical disease activity (p=0.16; p=0.44). No difference was found in IFX TLs between children receiving IFX monotherapy or concomitant immunosuppression. Conclusion: IFX TLs appear to be related to both clinical and biochemical disease activity (the latter measured by FC), which provides a rationale for therapeutic drug monitoring in children receiving IFX for IBD. Furthermore, a large variation in IFX TLs was found.
Categorical variables were compared using Pearson's Chi2 test or Fisher's exact test in cases where any sample size was less than 5. Continous variables, for which normal distribution was verified, were compared using Student's T-tests.
Tu1200 Impaired Remission in Pediatric Cronh`S Disease - Are Steroids to Blame? Jean-Pierre Gonçalves, Marta Tavares, Liliana Quaresma, Helena Rego, Ana Ratola, Eunice Trindade, Jorge Amil Objectives & Study: Exclusive enteral nutrition (EEN) is the standard recommendation for treatment of pediatric active Crohn's disease, and it induces high rate of histological remission (55%). Corticosteroids (CCT) are unlikely to promote mucosal healing and they may even cause deleterious effects (in-vitro model). To assess the clinical importance of this latter effect we compared a group of pediatric patients with newly diagnosed CD treated with EEN plus CCT. Methods: Among 99 new diagnosed active CD pediatric cases, clinical and laboratory data of 63 patients were retrospectively (1999-2013) reviewed, and the following data were recorded: demography, PCDAI at diagnosis and at 8, 12 and 52 weeks, additional therapy, and CD relapses. Results: In this study 63 cases were included and classified in the 3 treatment groups: 19 received CT, 11 EEN and 33 EEN plus CT. In G1 the steroid dose was 1 mg/kg/day; G2 received exclusive polymeric formula for 8 weeks (1500-2000 ml/day), and G3 received a combination of EEN (full dose) plus steroids (0.5mg/kg/d, max 20mg). For the majority, azathioprine was started in the first 8 weeks after diagnosis. There was no difference in age, initial PCDAI (G1 25; G2 20; G3 25), dose or timing of starting azathioprine or 5-ASA among the 3 groups. Of the 23 (36.5%) children who have relapsed in the follow-up: 10 received CT, 12 received CT+EEN, and 1 received EEN (p=0.058). All patients went into clinical remission at week 8 but the relapse rate of G1 (52.6%) and G2 (36.4%) during the first year was similar while G3 had lower relapse rate (9.1%). In G1, the relapse occurred at a median (min-max) time of 21.5 (8-52) weeks, in G2 it occurred at 22.5 (12-52) (p=0.619) and the single relapse in G3 occurred at 20 weeks. There was no significant difference in azathioprine dose. Biologics were required in 18.2% of G1, 9.7% of G2 group and none in G3. In 6 patients a second relapse was observed. Conclusion: To our knowledge this is the first observation comparing the clinical effect of combination of EEN with steroids and the observed results suggest that the addition of any dose of steroids to EEN may counteract the proven benefit of mucosal healing. Although these data are preliminary and group sizes are unequal there is a clear different outcome at 52 weeks. We
AGA Abstracts
Tu1202 Correlation Between Infliximab Levels (IFX) and Antibody to Infliximab (ATI) in Pediatric Patients With Inflammatory Bowel Disease (IBD) With the Commercially Available Assay Using Electrochemilumescense Edgardo D. Rivera Rivera, Chuanhong Liao, Kathleen Van't Hof, Thomas A. Mangatu, Stacy A. Kahn, Ranjana R. Gokhale, Barbara S. Kirschner Background: Immunogenicity against infliximab (IFX) is well established. Antibodies to infliximab (ATI) are often associated with loss of effect which can be an important limiting factor in the treatment of patients with moderate to severe IBD. However, a recent metaanalysis in adults with IBD demonstrated that ATI formation can be overcome by infliximab dose optimization (Nanda, KS, et al. Am J Gastroenterol 2013; 108:40). Aim: We sought to determine whether there is a relationship between IFX levels and ATI formation in a pediatric population utilizing a newly available commercial assay which uses electrochemilumescense (ECL) methodology. Methods: We performed a prospective observational study of pediatric patients receiving infliximab as part of the medical regimen for IBD [ulcerative colitis (UC), Crohn disease (CD) and indeterminate colitis (IC)]. Trough IFX and ATI levels were obtained in 69 consecutive patients: 54 patients as part of their maintenance regimen and 15 patients at the end of induction, with a commercially available assay using ECL methodology (Esoterix Endocrinology, Calabasas Hills, CA). Diagnosis, demographic data, medications, and doses were recorded. Results: Subjects were 52 % male. Mean age (±standard deviation) was 16.3 years (±3.0), 67% were <18 years of age and 33% were 18-22 years old. 85% had CD, 12% had UC, and 3% had IC. 36 patients were on concomitant therapy, 9 (25%) with thiopurines and 27 (75%) with methotrexate. The median dose of IFX was 6.0 mg/kg, with a range of 3.8 to 11.4. ATI's were detected in 28/69 (41%) of patients with median level of 113 ng/mL (range: 24-1304). The Spearman correlation coefficient between
S-782
speculate that steroids may interfere with the mucosal healing induced by polymeric diet reducing it and predisposing patients to earlier relapse of CD. Clinical characteristics by remission induction therapy
CT: corticosteroids; EEN: exclusive enteral nutrition *weeks ¥ at 8 weeks from start Tu1201 Large Variation in Infliximab Trough Levels Is Associated With Disease Activity in Paediatric Inflammatory Bowel Disease Daniël R. Hoekman, Johannan F. Brandse, Tim de Meij, Thalia Hummel, M. Lowenberg, Marc A. Benninga, Geert R. D'Haens, Angelika Kindermann Background: Low serum trough levels (TL) of infliximab (IFX) and the formation of antibodies to IFX (ATI) are associated with the loss of therapeutic response in adults with inflammatory bowel disease (IBD). Up until now, paediatric data are scarce. Therefore, we aimed to investigate the association between ATI and IFX TLs, and clinical and biochemical disease activity in children receiving maintenance treatment with IFX for IBD. Methods: All children aged <18 years receiving scheduled IFX maintenance treatment for Crohn's disease (CD) or ulcerative colitis (UC) in 3 tertiary hospitals in the Netherlands where asked to participate. Prior to two consecutive IFX infusions, IFX TL and ATI were measured. Therapeutic range of IFX was considered 3-7 μg/mL. Furthermore, biochemical disease activity was assessed by C-reactive protein (CRP) and faecal calprotectin (FC) (Bühlman ELISA). Clinical disease activity was determined by activity indices PCDAI and PUCAI, for CD and UC, respectively. Clinical remission was defined as a score of <10 for both PCDAI and PUCAI. A score of >30 or ≥65 was considered severe disease activity for PCDAI and PUCAI, respectively. Results: Between December 2012 and February 2013, thirty-three patients were included (26 CD, 7 UC), with a median age of 14 years [IQR 12-16]. All TL measurements combined (n=66), the median IFX TL was 3.0 μg/mL [IQR 1-6]. Subtherapeutic, therapeutic and supratherapeutic TLs were found in 42.4%, 39.4% and 18.2% of measurements, respectively. ATI were detected in 3 patients but our assay does not allow antibody detection in the presence of drug. Median FC and CRP was 394.5 μg/g and 2.4 mg/L, respectively. At both time points, the majority of patients were either in clinical remission (56.9%) or had mild to moderate clinical disease activity (41.2%). At the first measurement, no significant correlation between IFX TL and clinical or biochemical disease activity was found, although a trend was observed for FC (r=-0.33, p=0.08) and CRP (r=-0.331, p=0.06). At the second measurement, a significant correlation was found between IFX TL and clinical disease activity grading (r=-0.48, p=0.01) and FC (r=-0.49, p=0.01). Patients with therapeutic IFX TLs (≥3 μg/mL) were more likely to be in clinical remission (p=0.01). At both measurements, a significant correlation between clinical disease activity and FC was observed (r=0.53, p<0.01; r=0.50, p=0.02), whereas no correlation was found between CRP and clinical disease activity (p=0.16; p=0.44). No difference was found in IFX TLs between children receiving IFX monotherapy or concomitant immunosuppression. Conclusion: IFX TLs appear to be related to both clinical and biochemical disease activity (the latter measured by FC), which provides a rationale for therapeutic drug monitoring in children receiving IFX for IBD. Furthermore, a large variation in IFX TLs was found.
Categorical variables were compared using Pearson's Chi2 test or Fisher's exact test in cases where any sample size was less than 5. Continous variables, for which normal distribution was verified, were compared using Student's T-tests.
Tu1200 Impaired Remission in Pediatric Cronh`S Disease - Are Steroids to Blame? Jean-Pierre Gonçalves, Marta Tavares, Liliana Quaresma, Helena Rego, Ana Ratola, Eunice Trindade, Jorge Amil Objectives & Study: Exclusive enteral nutrition (EEN) is the standard recommendation for treatment of pediatric active Crohn's disease, and it induces high rate of histological remission (55%). Corticosteroids (CCT) are unlikely to promote mucosal healing and they may even cause deleterious effects (in-vitro model). To assess the clinical importance of this latter effect we compared a group of pediatric patients with newly diagnosed CD treated with EEN plus CCT. Methods: Among 99 new diagnosed active CD pediatric cases, clinical and laboratory data of 63 patients were retrospectively (1999-2013) reviewed, and the following data were recorded: demography, PCDAI at diagnosis and at 8, 12 and 52 weeks, additional therapy, and CD relapses. Results: In this study 63 cases were included and classified in the 3 treatment groups: 19 received CT, 11 EEN and 33 EEN plus CT. In G1 the steroid dose was 1 mg/kg/day; G2 received exclusive polymeric formula for 8 weeks (1500-2000 ml/day), and G3 received a combination of EEN (full dose) plus steroids (0.5mg/kg/d, max 20mg). For the majority, azathioprine was started in the first 8 weeks after diagnosis. There was no difference in age, initial PCDAI (G1 25; G2 20; G3 25), dose or timing of starting azathioprine or 5-ASA among the 3 groups. Of the 23 (36.5%) children who have relapsed in the follow-up: 10 received CT, 12 received CT+EEN, and 1 received EEN (p=0.058). All patients went into clinical remission at week 8 but the relapse rate of G1 (52.6%) and G2 (36.4%) during the first year was similar while G3 had lower relapse rate (9.1%). In G1, the relapse occurred at a median (min-max) time of 21.5 (8-52) weeks, in G2 it occurred at 22.5 (12-52) (p=0.619) and the single relapse in G3 occurred at 20 weeks. There was no significant difference in azathioprine dose. Biologics were required in 18.2% of G1, 9.7% of G2 group and none in G3. In 6 patients a second relapse was observed. Conclusion: To our knowledge this is the first observation comparing the clinical effect of combination of EEN with steroids and the observed results suggest that the addition of any dose of steroids to EEN may counteract the proven benefit of mucosal healing. Although these data are preliminary and group sizes are unequal there is a clear different outcome at 52 weeks. We
AGA Abstracts
Tu1202 Correlation Between Infliximab Levels (IFX) and Antibody to Infliximab (ATI) in Pediatric Patients With Inflammatory Bowel Disease (IBD) With the Commercially Available Assay Using Electrochemilumescense Edgardo D. Rivera Rivera, Chuanhong Liao, Kathleen Van't Hof, Thomas A. Mangatu, Stacy A. Kahn, Ranjana R. Gokhale, Barbara S. Kirschner Background: Immunogenicity against infliximab (IFX) is well established. Antibodies to infliximab (ATI) are often associated with loss of effect which can be an important limiting factor in the treatment of patients with moderate to severe IBD. However, a recent metaanalysis in adults with IBD demonstrated that ATI formation can be overcome by infliximab dose optimization (Nanda, KS, et al. Am J Gastroenterol 2013; 108:40). Aim: We sought to determine whether there is a relationship between IFX levels and ATI formation in a pediatric population utilizing a newly available commercial assay which uses electrochemilumescense (ECL) methodology. Methods: We performed a prospective observational study of pediatric patients receiving infliximab as part of the medical regimen for IBD [ulcerative colitis (UC), Crohn disease (CD) and indeterminate colitis (IC)]. Trough IFX and ATI levels were obtained in 69 consecutive patients: 54 patients as part of their maintenance regimen and 15 patients at the end of induction, with a commercially available assay using ECL methodology (Esoterix Endocrinology, Calabasas Hills, CA). Diagnosis, demographic data, medications, and doses were recorded. Results: Subjects were 52 % male. Mean age (±standard deviation) was 16.3 years (±3.0), 67% were <18 years of age and 33% were 18-22 years old. 85% had CD, 12% had UC, and 3% had IC. 36 patients were on concomitant therapy, 9 (25%) with thiopurines and 27 (75%) with methotrexate. The median dose of IFX was 6.0 mg/kg, with a range of 3.8 to 11.4. ATI's were detected in 28/69 (41%) of patients with median level of 113 ng/mL (range: 24-1304). The Spearman correlation coefficient between
S-782