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Su2078 Concomitant use of Adalimumab and Immunomodulators Compared With Adalimumab Alone: Pooled Malignancy Safety Analysis
ADA: adalimumab; CI: confidence interval; E: events; IMM: immunomodulators; NMSC: non-melanoma skin cancer; OR: odds ratio; PY: patient years. avs. ADA+no IMM. *, ** Significant at 0.05 or 0.01 level, respectively. Table 2. Observed and expected events and standardized incidence ratios with 95% CI.
Su2077 Antibodies Against Alfa Gliadin (AGA) and Deamidated Gliadin Peptides (DGP) in Patients With Autistic Spectrum Disorder (ASD) Anna Sapone, Annarita Picardi, Dario Siniscalco, Debora Angrisani, Patrizia Iardino, Carmela Bravaccio, Gabriele Riegler, Rita Cariello, Laura de Magistris, Alessio Fasano Background: Autism and autism spectrum disorders (ASDs) are enigmatic conditions that have their origins in the interaction between genes and environmental factors. Several studies suggest that increased gut-blood-brain-barrier permeability might be involved in the pathogenesis of these conditions. Recently, we have reported an increased intestinal permeability (IPT) “leaky gut” in a large percentage of not celiac autistic subjects that seemed be influenced by gluten-free diet. We can hypothesize that autistic patients(pts) are gluten sensitive, as well as it happens in other recently described conditions such as individuals with Schizophrenia. Aim: it was to evaluate antibody prevalence to gliadin (AGA), transglutaminase (tTG), deamidated gliadin peptides (DPG), endomysium (EMA) in a group of autistic pts with gastro-intestinal symptoms (GI) and/or altered IPT being on regular alimentary regimen (RAR) or on gluten-casein free diet (GCFD). Patients and methods: in 70 ASD children (54 RAR, 16 GFD) were performed serologic test combination representing Celiac Disease (CD): total serum IgA (sIgA), AGA, DGP, tTG, EMA IgA-IgG by ELISA and HLA haplotype by Eurospital Eu-DQ kit. Results: All pts had normal sIgA values and were negative for tTG, EMA (IgA and IgG); a low number of pts, 1/69 (1.40%) showed positive AGA-IgA in contrast to 22/70 (31.40%) with positive AGA IgG; out of 5 (7.10%) of these pts had also positive DGP IgG. Moreover, of the 22 AGA IgG positive pts, 50% (11) were HLA negative. Among the RAR pts, we found 38.90%( 21/54) AGA IgG positive, compared to only 6.30% (1/16) that were on GCFD. Interestingly, a large percentage of pts (90.5%) on RAR have impaired intestinal barrier function, while implementation of a GCFD normalizes intestinal barrier function in approximately 1/3 ( 38.7%) of ASD pts. Conclusions: Our preliminary results suggest that a sub-group of autistic children could have Gluten Sensitivity. The findings may have potential implications for the treatment of these subjects given that a GFD could contribute to the improvement of their symptoms.
ADA: adalimumab; CI: confidence interval; IMM: immunomodulators; NMSC: non-melanoma skin cancer; SIR: standardized incidence ratio. Su2079 Certolizumab Pegol Plasma Concentration and Clinical Remission in Crohn's Disease William J. Sandborn, Stephen B. Hanauer, Bosny Pierre-Louis, Gary R. Lichtenstein Purpose To explore the relationship between remission rates and certolizumab pegol (CZP) plasma concentrations in patients with active Crohn's disease after CZP induction therapy for 6 weeks and CZP open-label (OL) therapy for 6 weeks. Methods Patients completing the 6-week CZP induction study (study 085, NCT00552058), and with active disease (Crohn's Disease Activity Index [CDAI] score 220-450), were eligible to enter a CZP OL study (study 088, NCT00552344). Patients in the CZP induction study received CZP 400 mg induction therapy at Weeks 0, 2, and 4. In the CZP OL study, patients received openlabel CZP 400 mg at Weeks 0, 2, 4, and then every 4 weeks thereafter. In this post hoc analysis, remission rates were analyzed from the baseline of the CZP OL study (Week 0 in study 088, Week 6 in study 085). Blood samples for CZP plasma concentration were collected at Weeks 0 and 6 of the CZP OL study and analyzed by remission subgroup. Remission was defined as a CDAI score of ≤150. Remission rates were calculated using the intentionto-treat population (n=203). CZP plasma concentrations were evaluated in the safety population (n=206). Results A total of 203 patients (intention-to-treat population) received 6 weeks of CZP 400 mg induction therapy. At baseline of the CZP OL study (Week 0), the geometric mean CZP plasma concentration was 26.1 μg/mL. Among CZP plasma concentration quartiles, remission rates at Weeks 0, 2, 4, and 6 in the CZP OL study were higher among patients with CZP plasma concentrations in the highest two quartiles. Conclusions Patients with higher CZP plasma concentrations, defined as CZP concentrations in the highest 2 quartiles (CZP ≥27.5 μg/mL) had higher rates of remission at Weeks 0, 2, 4, and 6 as compared with patients with lower CZP concentrations. Further studies should be undertaken to determine if these patients will benefit from treatment optimization.
Su2078 Concomitant use of Adalimumab and Immunomodulators Compared With Adalimumab Alone: Pooled Malignancy Safety Analysis James D. Lewis, William J. Sandborn, Jean-Frederic Colombel, Mark T. Osterman, Anne Robinson, Winnie Lau, Bidan Huang, Paul F. Pollack, Roopal Thakkar Aim: An elevated risk of skin cancer and lymphomas has been reported in patients receiving thiopurines.1,2 We assessed the incidence of malignancies in patients with Crohn's disease (CD) using adalimumab (ADA) alone or in combination with immunomodulators (IMM). Methods: The proportion of patients with treatment-emergent malignancies was determined from the cumulative adverse event data in lead-in and long-term studies of ADA in CD (CLASSIC I and II, CHARM, GAIN, ADHERE, and EXTEND) among patients who received at least 1 dose of ADA. Two categories (non-melanoma skin cancer [NMSC] or all other types of malignancies) were assessed according to receipt of ADA+no IMM (ADA monotherapy without any IMM), ADA+any IMM (defined as azathioprine, mercaptopurine, or methotrexate), or ADA+thiopurine only at lead-in study baseline. IMM alone was not analyzed because of short duration of exposure due to open label crossover to ADA in most patients during long-term follow-up. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated using logistic regression; events per 100 patient years (PY) were compared using Poisson regression. Both analyses were run first without adjustment for covariates and then rerun adjusting for the following variables: previous anti-TNF use, baseline steroid use, baseline CDAI, age, race, sex, weight, disease duration, and smoking status. Standardized incidence ratios (SIRs, ratio of observed to expected number of cancers) and 95% CIs were calculated, using expected cancer rates based on age- and sex-specific cancer incidence data from the Surveillance Epidemiology and End Results (SEER) registry. In situ malignancies and certain other diagnoses not included in SEER were excluded from the SIR calculations. SIRs indicate whether the observed number of malignancies is less than (SIR <1.0) or greater than (SIR >1.0) that expected in an age- and sex-adjusted population. Results: 1594 patients (representing 3050 patient-years of exposure) were included in the pooled analysis. Proportions of patients with malignancies, ORs with CIs, event rates, and P-values are shown in Table 1. SIRs (with CIs) are shown in Table 2. For the non-skin cancer category, a variety of solid tumors in different organs were observed. There were 2 lymphomas, both in the ADA+IMM group, 1 of which occurred in the ADA+thiopurine group, and 1 acute myeloid leukemia (in the ADA+thiopurine group). Conclusion: The incidence of malignancy with
CI, confidence interval; Q, quartile.
S-563
AGA Abstracts
AGA Abstracts
adalimumab monotherapy was not elevated compared to expected rates, whereas incidence of malignancy with combination therapy was higher than expected in the general population and higher than with adalimumab monotherapy. References: 1. Beaugerie. Lancet. 2009;374:1617. 2. Peyrin-Biroulet. Gastroenterology. 2011; on-line. Table 1. Proportion of patients with malignancies, odds ratios with CIs, event rates, and P-values.
Su2077 Antibodies Against Alfa Gliadin (AGA) and Deamidated Gliadin Peptides (DGP) in Patients With Autistic Spectrum Disorder (ASD) Anna Sapone, Annarita Picardi, Dario Siniscalco, Debora Angrisani, Patrizia Iardino, Carmela Bravaccio, Gabriele Riegler, Rita Cariello, Laura de Magistris, Alessio Fasano Background: Autism and autism spectrum disorders (ASDs) are enigmatic conditions that have their origins in the interaction between genes and environmental factors. Several studies suggest that increased gut-blood-brain-barrier permeability might be involved in the pathogenesis of these conditions. Recently, we have reported an increased intestinal permeability (IPT) “leaky gut” in a large percentage of not celiac autistic subjects that seemed be influenced by gluten-free diet. We can hypothesize that autistic patients(pts) are gluten sensitive, as well as it happens in other recently described conditions such as individuals with Schizophrenia. Aim: it was to evaluate antibody prevalence to gliadin (AGA), transglutaminase (tTG), deamidated gliadin peptides (DPG), endomysium (EMA) in a group of autistic pts with gastro-intestinal symptoms (GI) and/or altered IPT being on regular alimentary regimen (RAR) or on gluten-casein free diet (GCFD). Patients and methods: in 70 ASD children (54 RAR, 16 GFD) were performed serologic test combination representing Celiac Disease (CD): total serum IgA (sIgA), AGA, DGP, tTG, EMA IgA-IgG by ELISA and HLA haplotype by Eurospital Eu-DQ kit. Results: All pts had normal sIgA values and were negative for tTG, EMA (IgA and IgG); a low number of pts, 1/69 (1.40%) showed positive AGA-IgA in contrast to 22/70 (31.40%) with positive AGA IgG; out of 5 (7.10%) of these pts had also positive DGP IgG. Moreover, of the 22 AGA IgG positive pts, 50% (11) were HLA negative. Among the RAR pts, we found 38.90%( 21/54) AGA IgG positive, compared to only 6.30% (1/16) that were on GCFD. Interestingly, a large percentage of pts (90.5%) on RAR have impaired intestinal barrier function, while implementation of a GCFD normalizes intestinal barrier function in approximately 1/3 ( 38.7%) of ASD pts. Conclusions: Our preliminary results suggest that a sub-group of autistic children could have Gluten Sensitivity. The findings may have potential implications for the treatment of these subjects given that a GFD could contribute to the improvement of their symptoms.
ADA: adalimumab; CI: confidence interval; IMM: immunomodulators; NMSC: non-melanoma skin cancer; SIR: standardized incidence ratio. Su2079 Certolizumab Pegol Plasma Concentration and Clinical Remission in Crohn's Disease William J. Sandborn, Stephen B. Hanauer, Bosny Pierre-Louis, Gary R. Lichtenstein Purpose To explore the relationship between remission rates and certolizumab pegol (CZP) plasma concentrations in patients with active Crohn's disease after CZP induction therapy for 6 weeks and CZP open-label (OL) therapy for 6 weeks. Methods Patients completing the 6-week CZP induction study (study 085, NCT00552058), and with active disease (Crohn's Disease Activity Index [CDAI] score 220-450), were eligible to enter a CZP OL study (study 088, NCT00552344). Patients in the CZP induction study received CZP 400 mg induction therapy at Weeks 0, 2, and 4. In the CZP OL study, patients received openlabel CZP 400 mg at Weeks 0, 2, 4, and then every 4 weeks thereafter. In this post hoc analysis, remission rates were analyzed from the baseline of the CZP OL study (Week 0 in study 088, Week 6 in study 085). Blood samples for CZP plasma concentration were collected at Weeks 0 and 6 of the CZP OL study and analyzed by remission subgroup. Remission was defined as a CDAI score of ≤150. Remission rates were calculated using the intentionto-treat population (n=203). CZP plasma concentrations were evaluated in the safety population (n=206). Results A total of 203 patients (intention-to-treat population) received 6 weeks of CZP 400 mg induction therapy. At baseline of the CZP OL study (Week 0), the geometric mean CZP plasma concentration was 26.1 μg/mL. Among CZP plasma concentration quartiles, remission rates at Weeks 0, 2, 4, and 6 in the CZP OL study were higher among patients with CZP plasma concentrations in the highest two quartiles. Conclusions Patients with higher CZP plasma concentrations, defined as CZP concentrations in the highest 2 quartiles (CZP ≥27.5 μg/mL) had higher rates of remission at Weeks 0, 2, 4, and 6 as compared with patients with lower CZP concentrations. Further studies should be undertaken to determine if these patients will benefit from treatment optimization.
Su2078 Concomitant use of Adalimumab and Immunomodulators Compared With Adalimumab Alone: Pooled Malignancy Safety Analysis James D. Lewis, William J. Sandborn, Jean-Frederic Colombel, Mark T. Osterman, Anne Robinson, Winnie Lau, Bidan Huang, Paul F. Pollack, Roopal Thakkar Aim: An elevated risk of skin cancer and lymphomas has been reported in patients receiving thiopurines.1,2 We assessed the incidence of malignancies in patients with Crohn's disease (CD) using adalimumab (ADA) alone or in combination with immunomodulators (IMM). Methods: The proportion of patients with treatment-emergent malignancies was determined from the cumulative adverse event data in lead-in and long-term studies of ADA in CD (CLASSIC I and II, CHARM, GAIN, ADHERE, and EXTEND) among patients who received at least 1 dose of ADA. Two categories (non-melanoma skin cancer [NMSC] or all other types of malignancies) were assessed according to receipt of ADA+no IMM (ADA monotherapy without any IMM), ADA+any IMM (defined as azathioprine, mercaptopurine, or methotrexate), or ADA+thiopurine only at lead-in study baseline. IMM alone was not analyzed because of short duration of exposure due to open label crossover to ADA in most patients during long-term follow-up. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated using logistic regression; events per 100 patient years (PY) were compared using Poisson regression. Both analyses were run first without adjustment for covariates and then rerun adjusting for the following variables: previous anti-TNF use, baseline steroid use, baseline CDAI, age, race, sex, weight, disease duration, and smoking status. Standardized incidence ratios (SIRs, ratio of observed to expected number of cancers) and 95% CIs were calculated, using expected cancer rates based on age- and sex-specific cancer incidence data from the Surveillance Epidemiology and End Results (SEER) registry. In situ malignancies and certain other diagnoses not included in SEER were excluded from the SIR calculations. SIRs indicate whether the observed number of malignancies is less than (SIR <1.0) or greater than (SIR >1.0) that expected in an age- and sex-adjusted population. Results: 1594 patients (representing 3050 patient-years of exposure) were included in the pooled analysis. Proportions of patients with malignancies, ORs with CIs, event rates, and P-values are shown in Table 1. SIRs (with CIs) are shown in Table 2. For the non-skin cancer category, a variety of solid tumors in different organs were observed. There were 2 lymphomas, both in the ADA+IMM group, 1 of which occurred in the ADA+thiopurine group, and 1 acute myeloid leukemia (in the ADA+thiopurine group). Conclusion: The incidence of malignancy with
CI, confidence interval; Q, quartile.
S-563
AGA Abstracts
AGA Abstracts
adalimumab monotherapy was not elevated compared to expected rates, whereas incidence of malignancy with combination therapy was higher than expected in the general population and higher than with adalimumab monotherapy. References: 1. Beaugerie. Lancet. 2009;374:1617. 2. Peyrin-Biroulet. Gastroenterology. 2011; on-line. Table 1. Proportion of patients with malignancies, odds ratios with CIs, event rates, and P-values.