- Email: [email protected]
Cost Analysis of Screening According to ECCO Guidelines for Prevention of Opportunistic Infections in Infliximab-Treated IBD Patients
AGA Abstracts
thiopurines significantly lower white blood cell counts were observed and all lymphocyte subpopulations except for CD56+ and CD8+ were similarly decreased. No significant changes in clinical activity scores or C-reactive protein levels were observed after vaccination. Conclusions: A single dose of influenza A H1N1 vaccine generated good humoral responses in thiopurine and TNF-α blockers treated IBD patients. IBD patients can be safely and effectively vaccinated against influenza A H1N1.
2. Elliott TR et al., Journal of Crohn's and Colitis, 4(1), 2010, S63 3. Fonseca JE et al, Acta Reumatol Port. 2006;31(3):247-53 Tu1226 Anti-TNF Therapy and Fetal Risk: A Systematic Review of the Literature Renee M. Marchioni, Caroline Kerner, Gary R. Lichtenstein
Tu1224
BACKGROUND & AIMS: Anti-tumor necrosis factor (TNF) therapy is effective for treatment of inflammatory bowel disease (IBD) refractory to conventional medical therapy. As the peak incidence of IBD overlaps with the prime reproductive years, it is crucial to quantify the risk of fetal harm and adverse birth outcomes in patients exposed to anti-TNF therapy in order to appropriately advise women of childbearing age requiring treatment for IBD. Published data regarding the safety of anti-TNF-alpha therapy during human pregnancy are limited, and consensus on the use of specific agents during this period has not been formally established. The aim of this study was to conduct a systematic literature review to assess the risk of adverse birth outcomes after maternal exposure to infliximab (IFX), adalimumab (ADA), or certolizumab pegol (CTZ). METHODS: A systematic review was performed. Databases included MEDLINE, EMBASE, SCOPUS, and BIOSYS using the search terms “inflammatory bowel disease,” “pregnancy,” “safety,” “congenital abnormalities,” “congenital disorders,” “infliximab,” “adalimumab,” and “certolizumab.” We included English-language published articles and abstracts pertaining to birth outcomes after maternal exposure to infliximab, adalimumab, or certolizumab pegol during any trimester of pregnancy. Reference lists of the relevant articles were hand-searched to identify additional studies. RESULTS: The initial search yielded 1566 citations. Thirty eight studies met inclusion criteria for full review. The included studies were 11 case series, 25 case reports, and 2 prospective studies with control groups. The total number of patients exposed to anti-TNF agents was 437 (IFX 189/ADA 230/CTZ 18). Of these, 369 exposures (84.4%) resulted in live births. Fifteen congenital abnormalities associated with live births (3.4%) were recorded (IFX 3/ADA 12/ CTZ 0). No pattern of specific birth defects was identified. Seventeen miscarriages, 18 spontaneous abortions, and 2 stillbirths were recorded for a total of 37 (8.5%) fetal deaths. Twelve preterm births (2.7%) were reported. These rates are similar to rates in the general population of pregnant women (http://ephtracking.cdc.gov) and women with IBD not exposed to anti-TNF agents (Dominitz J et al. Am J Gastroenterol 2002;97(3)641-8). Limitations of this review include small sample sizes, paucity of studies with control groups, and inability to adjust for concomitant medication use, comorbidities, or disease severity. CONCLUSION: These data suggest that the rates of congenital malformations and adverse birth events found are similar to the rates in the general population of pregnant women and women with IBD in general. Given the lack of controlled studies, there is insufficient evidence to prove absolute safety for the use of anti-TNFs during the preconception and pregnancy periods.
Does BMI Influence the Development of Hepatotoxicity in Patients With Inflammatory Bowel Disease (IBD) and Elevated 6MMP Levels? Anas Alsaleh, Jill Gaidos, John F. Valentine INTRODUCTION: Obesity is an increasing problem worldwide and over 30% of the US population is obese (BMI >25). Obesity increases susceptibility to hepatotoxicity from MTX in those with rheumatoid arthritis or psoriasis, cytotoxic chemotherapy in oncology patients, and anti-tuberculosis medications. Thiopurines (azathioprine and 6-MP) are commonly used in the treatment of IBD; however, hepatotoxicity is reported to occur in up to 17% of patients and can limit the use of these medications. A previous study identified corticosteroid use at the onset of thiopurine treatment as the only identifiable risk factor; however, the influence of BMI was not examined. In this study, we examined the influence of obesity on thiopurine hepatotoxicity in IBD patients with elevated 6-MMP levels. METHODS: The study was approved by the University of Florida IRB. A retrospective medical record search from a single IBD clinic at the University of Florida from 1999 to 2010 was conducted. All included patients had a confirmed diagnosis of IBD, documented 6-MMP level of >5700 pmol/8 x 10(8) erythrocytes and assessment of ALT and AST within the same time frame. Those with abnormal baseline ALT or AST were excluded. RESULTS: 52 patients were identified, 21 with normal ALT/AST, 32 with elevated ALT or AST. Of the eight patients with more than one elevated 6MMP, the date of the highest 6MMP was used. Of the patients with abnormal ALT or AST, 30 of 31 (97%) had an elevation in ALT. 25 of 31(80%) had an elevation in the AST. The mean age was 40.95 (range 19-71) and 46.78 (range 19-84) for those with normal or abnormal ALT/AST respectively. The group with abnormal ALT/ AST tended to be slightly older and had a higher percentage of men but this was not significant. The BMI was not significantly different between the two groups. All patients had normalization of the ALT/AST with dose reduction or change to an alternative therapy. One patient after her ALT/AST normalized developed primary sclerosing cholangitis. CONCLUSION: In this retrospective study from a single IBD clinic, BMI was not a factor for the development of elevated ALT or AST in IBD patients with elevated 6MMP levels. Patients with elevated ALT or AST were slightly older and had a higher M:F ratio, but these were not significant. All patients had normalization of the ALT/AST with dose reduction or change to an alternative therapy including low dose thiopurine plus allopurinol.
Tu1227 The Majority of Loss of Response to Infliximab is Not Due to Antibodies to Infliximab Somal Shah, Maria T. Abreu, James S. Leavitt Objective: The use of infliximab in IBD can lead to the formation of ATIsantibodies to infliximab (ATI's). The development of immunogenicity has been correlated with a decrease in drug concentration, clinical response, and the development of infusion reactions. While episodic use of infliximab and lack of concomitant immunomodulators with infliximab are known risk factors for the development of ATIs, other potential risk factors such as patient age and time on infliximab have not been extensively studied. Additionally, the utility of checking ATIs in patients with an infusion reaction to infliximab is unclear.Methods: The medical records of patients with inflammatory bowel disease treated with infliximab at our institution between 2008 to 2010 were identified. Medical charts for patients who were checked for ATIs and/or had documented infusion reactions were retrospectively reviewed. The patients were grouped by positive vs. negative ATIs levels and then compared in terms of demographic variables such as age, time on infliximab, and concurrent use of immunomodulators. Results: A total of 41 patients were identified for inclusion in this study. The reason for checking ATIs included diminished response to infliximab, documented infusion/delayed hypersensitivity, and planned re-introduction to infliximab after prior treatment. 9 patients were found to be positive for ATIs, while 29 were ATIs negative. The average age of the patients in the ATI positive group was 41.7 years compared to 41.0 years in the ATI negative group (p-value= 0.91). The average time on infliximab for the ATI positive group was 16.6 months as compared to 19.3 months for the ATI negative group (p-value= 0.78). A total of 13 patients were on concurrent immunomodulators, 2 in the ATI+ group and 11 in the ATI-negative group. There were 10 patients that had a documented infusion reaction; 7 of these patients were checked for ATIs. 2 /7 of these patients were found to be ATI negative. Both of these patients were continued on infliximab rather than switching to another anti-TNF agent.Conclusion: Time on infliximab and age is not predictive for the development of ATIs. Treatment with immunomodulators is not protective against loss of response to infliximab. Not all patients with an infusion reaction are ATI+ and thus can continue treatment with infliximab. A surprising minority of patients lose response to infliximab because of ATIs. These findings could speak to insensitivity of the ATI assay or other mechanisms of loss of response.
Tu1225 Cost Analysis of Screening According to ECCO Guidelines for Prevention of Opportunistic Infections in Infliximab-Treated IBD Patients Andrew J. Metz, Tim Elliott, Bradley Hull, Julie Duncan, Marlene Sastrillo, Melissa A. Smith, Jeremy D. Sanderson, Peter M. Irving Introduction: We previously reported that our practice of screening for and prevention of opportunistic infections (OI's) in at risk IBD patients was not in line with ECCO recommendations [1,2]. In this study, we aimed firstly to seek evidence of OI's in our historical cohort of infliximab (IFX)-treated patients who had not been screened according to recommendations and secondly, to analyse the cost-effectiveness of screening of, and prophylaxis as required for tuberculosis (TB) and hepatitis B (hep B) in IFX-treated patients. Methods: An audit of consecutive patients treated with IFX (2005-2009) was conducted and ocurrence of OIs and duration of IFX were recorded. A cost-minimisation analysis was performed using clinical decision analytic modelling to assess cost outcome of screening and prevention versus not screening and prevention. Model branch probabilities were obtained from a Medline search. The cost perspective was the health sector. Hospital admissions were based on Healthcare Resource Group (HRG4) codes. Results: There were no OI's identified in 92 IBD patients treated with a median of 21 months of IFX. For 1000 hypothetical Crohn's patients in a western European population, the model predicted 15 screened patients required isoniazid prophylaxis, with 0.5 unscreened patients admitted to hospital with TB. There was an incremental cost for screening of US$61.30/patient for CXR alone, or $194.90 for CXR combined with an interferon release assay. Conversely, there was a cost saving for screening in Southern Europe ($18.60/patient). For Hepatitis B in the Western European population, the model predicted 35.7 screened patients required lamivudine prophylaxis, whereas in the unscreened group, 2 patients reactivated with hepatitis, 3 patients with liver failure, and one required a transplant. There was a cost saving of $49.70/patient for screening. Conclusion: There were no significant OI's identified in this audit of IFX-treated IBD patients despite failure to screen according to ECCO guidelines. The cost analysis model demonstrates cost saving for hepatitis B screening because of the significant cost of hepatitis B reactivation. In the southern European population there is a cost benefit for TB screening due to a high rate of latent TB whereas in the western European population, there is an incremental cost for screening because of a lower risk of TB reactivation there. This cost should be balanced against the risk of death due to TB reactivation (reported in Southern but not Western Europe) [3]. References: 1. Rahier JF et al., Journal of Crohn's and Colitis, 3(2), 2009, p47
AGA Abstracts
Tu1228 Lipid Profile Changes in Patients With Inflammatory Bowel Disease (IBD) Treated With Anti-Tumor Necrosis-Alpha Antagonists Maria Cappello, Loretta Amato, Ivana Bravatà, Claudia Randazzo, Piero Almasio, Antonio Craxì Introduction. Previous studies in patients with rheumatoid arthritis or ankylosing spondilytis have shown that anti-tumor necrosis factor-alpha agents may alter lipid profile and reduce the atherogenic risk. Data on patients with Inflammatory Bowel Disease (IBD) are lacking.
S-772
thiopurines significantly lower white blood cell counts were observed and all lymphocyte subpopulations except for CD56+ and CD8+ were similarly decreased. No significant changes in clinical activity scores or C-reactive protein levels were observed after vaccination. Conclusions: A single dose of influenza A H1N1 vaccine generated good humoral responses in thiopurine and TNF-α blockers treated IBD patients. IBD patients can be safely and effectively vaccinated against influenza A H1N1.
2. Elliott TR et al., Journal of Crohn's and Colitis, 4(1), 2010, S63 3. Fonseca JE et al, Acta Reumatol Port. 2006;31(3):247-53 Tu1226 Anti-TNF Therapy and Fetal Risk: A Systematic Review of the Literature Renee M. Marchioni, Caroline Kerner, Gary R. Lichtenstein
Tu1224
BACKGROUND & AIMS: Anti-tumor necrosis factor (TNF) therapy is effective for treatment of inflammatory bowel disease (IBD) refractory to conventional medical therapy. As the peak incidence of IBD overlaps with the prime reproductive years, it is crucial to quantify the risk of fetal harm and adverse birth outcomes in patients exposed to anti-TNF therapy in order to appropriately advise women of childbearing age requiring treatment for IBD. Published data regarding the safety of anti-TNF-alpha therapy during human pregnancy are limited, and consensus on the use of specific agents during this period has not been formally established. The aim of this study was to conduct a systematic literature review to assess the risk of adverse birth outcomes after maternal exposure to infliximab (IFX), adalimumab (ADA), or certolizumab pegol (CTZ). METHODS: A systematic review was performed. Databases included MEDLINE, EMBASE, SCOPUS, and BIOSYS using the search terms “inflammatory bowel disease,” “pregnancy,” “safety,” “congenital abnormalities,” “congenital disorders,” “infliximab,” “adalimumab,” and “certolizumab.” We included English-language published articles and abstracts pertaining to birth outcomes after maternal exposure to infliximab, adalimumab, or certolizumab pegol during any trimester of pregnancy. Reference lists of the relevant articles were hand-searched to identify additional studies. RESULTS: The initial search yielded 1566 citations. Thirty eight studies met inclusion criteria for full review. The included studies were 11 case series, 25 case reports, and 2 prospective studies with control groups. The total number of patients exposed to anti-TNF agents was 437 (IFX 189/ADA 230/CTZ 18). Of these, 369 exposures (84.4%) resulted in live births. Fifteen congenital abnormalities associated with live births (3.4%) were recorded (IFX 3/ADA 12/ CTZ 0). No pattern of specific birth defects was identified. Seventeen miscarriages, 18 spontaneous abortions, and 2 stillbirths were recorded for a total of 37 (8.5%) fetal deaths. Twelve preterm births (2.7%) were reported. These rates are similar to rates in the general population of pregnant women (http://ephtracking.cdc.gov) and women with IBD not exposed to anti-TNF agents (Dominitz J et al. Am J Gastroenterol 2002;97(3)641-8). Limitations of this review include small sample sizes, paucity of studies with control groups, and inability to adjust for concomitant medication use, comorbidities, or disease severity. CONCLUSION: These data suggest that the rates of congenital malformations and adverse birth events found are similar to the rates in the general population of pregnant women and women with IBD in general. Given the lack of controlled studies, there is insufficient evidence to prove absolute safety for the use of anti-TNFs during the preconception and pregnancy periods.
Does BMI Influence the Development of Hepatotoxicity in Patients With Inflammatory Bowel Disease (IBD) and Elevated 6MMP Levels? Anas Alsaleh, Jill Gaidos, John F. Valentine INTRODUCTION: Obesity is an increasing problem worldwide and over 30% of the US population is obese (BMI >25). Obesity increases susceptibility to hepatotoxicity from MTX in those with rheumatoid arthritis or psoriasis, cytotoxic chemotherapy in oncology patients, and anti-tuberculosis medications. Thiopurines (azathioprine and 6-MP) are commonly used in the treatment of IBD; however, hepatotoxicity is reported to occur in up to 17% of patients and can limit the use of these medications. A previous study identified corticosteroid use at the onset of thiopurine treatment as the only identifiable risk factor; however, the influence of BMI was not examined. In this study, we examined the influence of obesity on thiopurine hepatotoxicity in IBD patients with elevated 6-MMP levels. METHODS: The study was approved by the University of Florida IRB. A retrospective medical record search from a single IBD clinic at the University of Florida from 1999 to 2010 was conducted. All included patients had a confirmed diagnosis of IBD, documented 6-MMP level of >5700 pmol/8 x 10(8) erythrocytes and assessment of ALT and AST within the same time frame. Those with abnormal baseline ALT or AST were excluded. RESULTS: 52 patients were identified, 21 with normal ALT/AST, 32 with elevated ALT or AST. Of the eight patients with more than one elevated 6MMP, the date of the highest 6MMP was used. Of the patients with abnormal ALT or AST, 30 of 31 (97%) had an elevation in ALT. 25 of 31(80%) had an elevation in the AST. The mean age was 40.95 (range 19-71) and 46.78 (range 19-84) for those with normal or abnormal ALT/AST respectively. The group with abnormal ALT/ AST tended to be slightly older and had a higher percentage of men but this was not significant. The BMI was not significantly different between the two groups. All patients had normalization of the ALT/AST with dose reduction or change to an alternative therapy. One patient after her ALT/AST normalized developed primary sclerosing cholangitis. CONCLUSION: In this retrospective study from a single IBD clinic, BMI was not a factor for the development of elevated ALT or AST in IBD patients with elevated 6MMP levels. Patients with elevated ALT or AST were slightly older and had a higher M:F ratio, but these were not significant. All patients had normalization of the ALT/AST with dose reduction or change to an alternative therapy including low dose thiopurine plus allopurinol.
Tu1227 The Majority of Loss of Response to Infliximab is Not Due to Antibodies to Infliximab Somal Shah, Maria T. Abreu, James S. Leavitt Objective: The use of infliximab in IBD can lead to the formation of ATIsantibodies to infliximab (ATI's). The development of immunogenicity has been correlated with a decrease in drug concentration, clinical response, and the development of infusion reactions. While episodic use of infliximab and lack of concomitant immunomodulators with infliximab are known risk factors for the development of ATIs, other potential risk factors such as patient age and time on infliximab have not been extensively studied. Additionally, the utility of checking ATIs in patients with an infusion reaction to infliximab is unclear.Methods: The medical records of patients with inflammatory bowel disease treated with infliximab at our institution between 2008 to 2010 were identified. Medical charts for patients who were checked for ATIs and/or had documented infusion reactions were retrospectively reviewed. The patients were grouped by positive vs. negative ATIs levels and then compared in terms of demographic variables such as age, time on infliximab, and concurrent use of immunomodulators. Results: A total of 41 patients were identified for inclusion in this study. The reason for checking ATIs included diminished response to infliximab, documented infusion/delayed hypersensitivity, and planned re-introduction to infliximab after prior treatment. 9 patients were found to be positive for ATIs, while 29 were ATIs negative. The average age of the patients in the ATI positive group was 41.7 years compared to 41.0 years in the ATI negative group (p-value= 0.91). The average time on infliximab for the ATI positive group was 16.6 months as compared to 19.3 months for the ATI negative group (p-value= 0.78). A total of 13 patients were on concurrent immunomodulators, 2 in the ATI+ group and 11 in the ATI-negative group. There were 10 patients that had a documented infusion reaction; 7 of these patients were checked for ATIs. 2 /7 of these patients were found to be ATI negative. Both of these patients were continued on infliximab rather than switching to another anti-TNF agent.Conclusion: Time on infliximab and age is not predictive for the development of ATIs. Treatment with immunomodulators is not protective against loss of response to infliximab. Not all patients with an infusion reaction are ATI+ and thus can continue treatment with infliximab. A surprising minority of patients lose response to infliximab because of ATIs. These findings could speak to insensitivity of the ATI assay or other mechanisms of loss of response.
Tu1225 Cost Analysis of Screening According to ECCO Guidelines for Prevention of Opportunistic Infections in Infliximab-Treated IBD Patients Andrew J. Metz, Tim Elliott, Bradley Hull, Julie Duncan, Marlene Sastrillo, Melissa A. Smith, Jeremy D. Sanderson, Peter M. Irving Introduction: We previously reported that our practice of screening for and prevention of opportunistic infections (OI's) in at risk IBD patients was not in line with ECCO recommendations [1,2]. In this study, we aimed firstly to seek evidence of OI's in our historical cohort of infliximab (IFX)-treated patients who had not been screened according to recommendations and secondly, to analyse the cost-effectiveness of screening of, and prophylaxis as required for tuberculosis (TB) and hepatitis B (hep B) in IFX-treated patients. Methods: An audit of consecutive patients treated with IFX (2005-2009) was conducted and ocurrence of OIs and duration of IFX were recorded. A cost-minimisation analysis was performed using clinical decision analytic modelling to assess cost outcome of screening and prevention versus not screening and prevention. Model branch probabilities were obtained from a Medline search. The cost perspective was the health sector. Hospital admissions were based on Healthcare Resource Group (HRG4) codes. Results: There were no OI's identified in 92 IBD patients treated with a median of 21 months of IFX. For 1000 hypothetical Crohn's patients in a western European population, the model predicted 15 screened patients required isoniazid prophylaxis, with 0.5 unscreened patients admitted to hospital with TB. There was an incremental cost for screening of US$61.30/patient for CXR alone, or $194.90 for CXR combined with an interferon release assay. Conversely, there was a cost saving for screening in Southern Europe ($18.60/patient). For Hepatitis B in the Western European population, the model predicted 35.7 screened patients required lamivudine prophylaxis, whereas in the unscreened group, 2 patients reactivated with hepatitis, 3 patients with liver failure, and one required a transplant. There was a cost saving of $49.70/patient for screening. Conclusion: There were no significant OI's identified in this audit of IFX-treated IBD patients despite failure to screen according to ECCO guidelines. The cost analysis model demonstrates cost saving for hepatitis B screening because of the significant cost of hepatitis B reactivation. In the southern European population there is a cost benefit for TB screening due to a high rate of latent TB whereas in the western European population, there is an incremental cost for screening because of a lower risk of TB reactivation there. This cost should be balanced against the risk of death due to TB reactivation (reported in Southern but not Western Europe) [3]. References: 1. Rahier JF et al., Journal of Crohn's and Colitis, 3(2), 2009, p47
AGA Abstracts
Tu1228 Lipid Profile Changes in Patients With Inflammatory Bowel Disease (IBD) Treated With Anti-Tumor Necrosis-Alpha Antagonists Maria Cappello, Loretta Amato, Ivana Bravatà, Claudia Randazzo, Piero Almasio, Antonio Craxì Introduction. Previous studies in patients with rheumatoid arthritis or ankylosing spondilytis have shown that anti-tumor necrosis factor-alpha agents may alter lipid profile and reduce the atherogenic risk. Data on patients with Inflammatory Bowel Disease (IBD) are lacking.
S-772