1
is confirmed between TST and IGRA, in IBD subjects. BCG vaccination and immunosuppres- sion have no influence on each test. IGRA seems to turn out negative by TNF alpha inhibitor Therapy. Indeed, without biological drugs, as well as chest X- rays, screening must be performed with TST and IGRA association. For older than 59 years patients, IGRA must be proposed. With biological drugs, IGRA is less efficient, TST alone has to be chosen. W1201 The Risk of Infectious Complications Associated With the use of Immunosuppressive Medications in Elderly Patients With Inflammatory Bowel Disease Ming V. Lin, Wojciech Blonski, Faten Aberra, Colleen M. Brensinger, Irene Sonu, Gary Lichtenstein Background: The use of immunsuppressive agents (ISA) is associated with (a/w) significant adverse events,including infectious complications (IC) in IBD pts. In the TREAT registry (CGH 2006;4:621-630) age and prednisone use in IBD pts were a/w increased mortality and IC. The use of infliximab was suggested to be a/w an increased mortality rate in elderly pts treated for IBD (Gastroenterology 2004;126:19-31). 6-MP/azathioprine was well tolerated by the elderly in an uncontrolled trial (AJG 2009;14:1171). No studies were published comparing IC a/w the different immunosuppressive medications between elderly and young. Aim: To assess if age is an independent risk factor for prediction of IC in IBD pts exposed to ISA. Methods: We searched our electronic medical records to identify pts with CD/UC aged >17 between 2007-2009. Pts with cancer, immunodeficiency and exposure to ISA for other reasons were excluded. Data on demographics, IBD subtypes, co-morbidities, medica- tion details and infections were collected and analyzed. Results: 48 pts with IBD and age >65 yrs and 162 pts with IBD and age <35 but >17 yrs were identified. The demographics, IBD subtypes, co-morbidities (e.g. DM, CHF, CAD, CKD/CRF, cirrhosis, obesity and depres- sion) and IC are in Table 1. The ISA exposures for both groups are in Table 2. Elderly pts were 5 times more likely to have IC compared to young pts (OR=5.07, 95% CI 1.87-13.70, p=0.0014). Pts with co-morbidities were 8 times more likely to develop infections (OR= 8.60, 95% CI 3.06-24.18, p<0.0001)than pts without co-morbidities. 5% of young pts, 10% of elderly without co-morbidities, and 30% of elderly with co-morbidities had IC (p=0.0006). In the multivariable logistic regression model for risk of IC, age and co-morbidity were the only predictors a/w significant increase of IC. Sex, race, IBD subtype, CS/IMM/Bio exposure were not significantly a/w IC when comparing the two groups. Conclusion: There is an increased risk of IC in the elderly. Age and co-existing co-morbidities are independent risk factors for prediction of IC in IBD pts exposed to ISA. Table 1 Table 2 W1202 Can Low Dose Azathioprine or 6-Mercaptopurine in Combination With Allopurinol Bypass Some Non-Hepatitic Adverse Drug Reactions and Procure a Good Treatment Response in IBD? Azhar Ansari, Nisha Patel, Jeremy D. Sanderson, John A. Duley, Timothy H. Florin, John O'Donohue BACKGROUND The thiopurines drugs, azathioprine (AZA) and 6-meracaptopurine (6- MP), are important therapies for inflammatory bowel disease (IBD). However, adverse drug reactions (ADRs) or poor response can result in the use of less established therapies. We report our experience using reduced dose thipurines with allopurinol as co-therapy to by- pass ADRs and obtain response. METHODS This was an open label study of 41 patients, ages of 16 and 80 years with IBD who had had ADRs to full dose thiopurines at two centres. Reduced dose thiopurine in combination with allopurinol was given. Dosing was guided by measuring thiopurine methyltransferase (for UK patients) and thioguanine nucleotides and methyl-6MP (for Australian patients). Clinical response was monitored with clinical activity indices. RESULTS Of the 41 patients, 25 had non-hepatic and 16 had hepatitic ADRs. Clinical remission was achieved in 32 patients (78%) with a mean of follow-up of 41 weeks (range 0.5-400). Failure of response to the combination therapy manifested early, median 5 weeks (range 0.5-42). CONCLUSION In IBD patients, low dose thiopurine and allopurinol co-therapy was successful at by-passing ADRs whilst returning a good long-term response. This is the first case series providing evidence to support a combination therapy in patients who have had thiopurine related side effects, including non-hepatitic ADRs. S-673 AGA Abstracts W1203 CMV Specific T Cell Response is Conserved in IBD Patients Davide Checchin, Davide Abate, Barbara Mantelli, Roberta Caccaro, Giacomo C. Sturniolo, Renata D'Incà BACKGROUND AND AIMS Inflammatory bowel disease (IBD) is characterized by an imbal- anced and deregulated immune system. Human Cytomegalovirus (CMV) infection has been implicated in IBD perpetuation. It is still debated if CMV plays a role in IBD or it is just an innocent bystander. Aim of this study was to assess of CMV specific T-cell response in IBD patients in peripheral blood and to relate immune response to CMV and type of treatment. METHODS Anti-CMV IgG antibodies and CMV specific IFN-γ ELISPOT assay were measured in peripheral blood mononuclear cells (PBMCs) in IBD patients and volunteer donors. Cut-off for negative immunity was set at 20 IFN-γ ELISPOT forming colonies/ 200000 PBMCs. Data are expressed as median and interquartile range (IQR) with analysis by Mann Whitney for IFN-γ expression and Fisher exact test when appropriated. RESULTS Sixty-three patients were enrolled in the study. Anti CMV IgG antibodies were detected in 37/62 (59.2%) patients that were included (16 UC, 21 CD; 15/37 of them receiving standard anti-inflammatory treatment and 22/37 either azathioprine, steroids>20 mg>/die or biologic drugs). Median IFN-γ ELISPOT forming colonies/200000 PBMCs were different in IBD patients with respect to controls 139 (IQR 59-211) vs 77 (IQR 42-126); p=0.25, see figure) Negative response was observed in 6 IDB patients and none of the controls. Immunosuppress- ive drugs were not associated with low IFN-g ELISPOT response (see tab). An abnormal CD8 expression was detected on γδ T-cells in one patient with a positive family history for γδ lymphoma. DISCUSSION AND CONCLUSION Standard maintenance therapy regimen does not reduce significantly significantly median IFNg expression. Negative CMV specific T- cell response was detected in 10% of IBD patients and was not related to immunosuppressive therapy. Since CMV benefits from the pro-inflammatory environment of the IBD mucosal lesions, patients with inappropriate response need careful assessment. Further characteriza- tion of γδ T-cell and CMV specific T-cell response needs to be performed in diseased tissues. Fisher Exact test; ns. Th= azathioprine, steroids>20 mg>/die or biologic drugs. AGA Abstracts

W1201 The Risk of Infectious Complications Associated With the use of Immunosuppressive Medications in Elderly Patients With Inflammatory Bowel Disease

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Page 1: W1201 The Risk of Infectious Complications Associated With the use of Immunosuppressive Medications in Elderly Patients With Inflammatory Bowel Disease

is confirmed between TST and IGRA, in IBD subjects. BCG vaccination and immunosuppres-sion have no influence on each test. IGRA seems to turn out negative by TNF alpha inhibitorTherapy. Indeed, without biological drugs, as well as chest X- rays, screening must beperformed with TST and IGRA association. For older than 59 years patients, IGRA must beproposed. With biological drugs, IGRA is less efficient, TST alone has to be chosen.

W1201

The Risk of Infectious Complications Associated With the use ofImmunosuppressive Medications in Elderly Patients With Inflammatory BowelDiseaseMing V. Lin, Wojciech Blonski, Faten Aberra, Colleen M. Brensinger, Irene Sonu, GaryLichtenstein

Background: The use of immunsuppressive agents (ISA) is associated with (a/w) significantadverse events,including infectious complications (IC) in IBD pts. In the TREAT registry(CGH 2006;4:621-630) age and prednisone use in IBD pts were a/w increased mortalityand IC. The use of infliximab was suggested to be a/w an increased mortality rate in elderlypts treated for IBD (Gastroenterology 2004;126:19-31). 6-MP/azathioprine was well toleratedby the elderly in an uncontrolled trial (AJG 2009;14:1171). No studies were publishedcomparing IC a/w the different immunosuppressive medications between elderly and young.Aim: To assess if age is an independent risk factor for prediction of IC in IBD pts exposedto ISA. Methods: We searched our electronic medical records to identify pts with CD/UCaged >17 between 2007-2009. Pts with cancer, immunodeficiency and exposure to ISA forother reasons were excluded. Data on demographics, IBD subtypes, co-morbidities, medica-tion details and infections were collected and analyzed. Results: 48 pts with IBD and age>65 yrs and 162 pts with IBD and age <35 but >17 yrs were identified. The demographics,IBD subtypes, co-morbidities (e.g. DM, CHF, CAD, CKD/CRF, cirrhosis, obesity and depres-sion) and IC are in Table 1. The ISA exposures for both groups are in Table 2. Elderly ptswere 5 times more likely to have IC compared to young pts (OR=5.07, 95% CI 1.87-13.70,p=0.0014). Pts with co-morbidities were 8 times more likely to develop infections (OR=8.60, 95% CI 3.06-24.18, p<0.0001)than pts without co-morbidities. 5% of young pts, 10%of elderly without co-morbidities, and 30% of elderly with co-morbidities had IC (p=0.0006).In the multivariable logistic regression model for risk of IC, age and co-morbidity were theonly predictors a/w significant increase of IC. Sex, race, IBD subtype, CS/IMM/Bio exposurewere not significantly a/w IC when comparing the two groups. Conclusion: There is anincreased risk of IC in the elderly. Age and co-existing co-morbidities are independent riskfactors for prediction of IC in IBD pts exposed to ISA.Table 1

Table 2

W1202

Can Low Dose Azathioprine or 6-Mercaptopurine in Combination WithAllopurinol Bypass Some Non-Hepatitic Adverse Drug Reactions and Procure aGood Treatment Response in IBD?Azhar Ansari, Nisha Patel, Jeremy D. Sanderson, John A. Duley, Timothy H. Florin, JohnO'Donohue

BACKGROUND The thiopurines drugs, azathioprine (AZA) and 6-meracaptopurine (6-MP), are important therapies for inflammatory bowel disease (IBD). However, adverse drugreactions (ADRs) or poor response can result in the use of less established therapies. Wereport our experience using reduced dose thipurines with allopurinol as co-therapy to by-pass ADRs and obtain response. METHODS This was an open label study of 41 patients,ages of 16 and 80 years with IBD who had had ADRs to full dose thiopurines at two centres.Reduced dose thiopurine in combination with allopurinol was given. Dosing was guidedby measuring thiopurine methyltransferase (for UK patients) and thioguanine nucleotidesand methyl-6MP (for Australian patients). Clinical response was monitored with clinicalactivity indices. RESULTS Of the 41 patients, 25 had non-hepatic and 16 had hepatiticADRs. Clinical remission was achieved in 32 patients (78%) with a mean of follow-up of41 weeks (range 0.5-400). Failure of response to the combination therapy manifested early,median 5 weeks (range 0.5-42). CONCLUSION In IBD patients, low dose thiopurine andallopurinol co-therapy was successful at by-passing ADRs whilst returning a good long-termresponse. This is the first case series providing evidence to support a combination therapyin patients who have had thiopurine related side effects, including non-hepatitic ADRs.

S-673 AGA Abstracts

W1203

CMV Specific T Cell Response is Conserved in IBD PatientsDavide Checchin, Davide Abate, Barbara Mantelli, Roberta Caccaro, Giacomo C.Sturniolo, Renata D'Incà

BACKGROUND AND AIMS Inflammatory bowel disease (IBD) is characterized by an imbal-anced and deregulated immune system. Human Cytomegalovirus (CMV) infection has beenimplicated in IBD perpetuation. It is still debated if CMV plays a role in IBD or it is justan innocent bystander. Aim of this study was to assess of CMV specific T-cell response inIBD patients in peripheral blood and to relate immune response to CMV and type oftreatment. METHODS Anti-CMV IgG antibodies and CMV specific IFN-γ ELISPOT assaywere measured in peripheral blood mononuclear cells (PBMCs) in IBD patients and volunteerdonors. Cut-off for negative immunity was set at 20 IFN-γ ELISPOT forming colonies/200000 PBMCs. Data are expressed as median and interquartile range (IQR) with analysisby Mann Whitney for IFN-γ expression and Fisher exact test when appropriated. RESULTSSixty-three patients were enrolled in the study. Anti CMV IgG antibodies were detected in37/62 (59.2%) patients that were included (16 UC, 21 CD; 15/37 of them receiving standardanti-inflammatory treatment and 22/37 either azathioprine, steroids>20 mg>/die or biologicdrugs). Median IFN-γ ELISPOT forming colonies/200000 PBMCs were different in IBDpatients with respect to controls 139 (IQR 59-211) vs 77 (IQR 42-126); p=0.25, see figure)Negative response was observed in 6 IDB patients and none of the controls. Immunosuppress-ive drugs were not associated with low IFN-g ELISPOT response (see tab). An abnormalCD8 expression was detected on γδ T-cells in one patient with a positive family history forγδ lymphoma. DISCUSSION AND CONCLUSION Standard maintenance therapy regimendoes not reduce significantly significantly median IFNg expression. Negative CMV specific T-cell response was detected in 10% of IBD patients and was not related to immunosuppressivetherapy. Since CMV benefits from the pro-inflammatory environment of the IBD mucosallesions, patients with inappropriate response need careful assessment. Further characteriza-tion of γδ T-cell and CMV specific T-cell response needs to be performed in diseased tissues.

Fisher Exact test; ns. Th= azathioprine, steroids>20 mg>/die or biologic drugs.

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