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P.05.3 COMPLEX PERIANAL CROHN'S DISEASE: EFFECTIVENESS OF COMBINED SETON PLACEMENT AND ANTI-TNF ALPHA AGENTS IN MONOTHERAPY OR IN ASSOCIATION WITH IMMUNOSUPPRESSANTS
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Abstracts of the 18th National Congress of Digestive Diseases / Digestive and Liver Disease 44S (2012) S55–S220
P.05.2 PATHOGENIC ROLE OF IL-33-MEDIATED EOS INFILTRATION AND FUNCTION IN EXPERIMENTAL INFLAMMATORY BOWEL DISEASE C. De Salvo ∗ ,1 , X.M. Wang 1 , B. Mattioli 1 , L. Pastorelli 1 , R. Garg 1 , S. Chowhdry 1 , W. Xin 1 , M. Vecchi 2 , T. Pizarro 1 1 Case
Western Reserve University, Cleveland, Oh, United States; 2 Irccs Policlinico San Donato, San Donato Milanese (Mi), Italy Background and aim: IL-33, a new member of the IL-1 family, is linked to several immune and inflammatory disorders, such as IBD. Eosinophils (EOS) are found in active inflammatory lesions of IBD patients and can secrete proinflammatory molecules, alter epithelial barrier function and initiate mucosal immune responses leading to chronic gut inflammation. Recent evidence show that IL-33 can regulate EOS infiltration and function. The aim of this study is to determine IL-33-mediated EOS activation and ileal inflammation in the SAMP1/YitFc (SAMP) murine model of chronic enteritis. Material and methods: EOS were detected by IHC for major basic protein (MBP). IL-33 and EOS-associated cytokines, IL-5 and eotaxin-1,-2,-3, were measured by qPCR in a timecourse study of SAMP and AKR (parental control) ilea. Th2 cytokines were measured by ELISA in mesenteric lymph nodes (MLN) of SAMP treated daily with rIL-33 (33 ug/kg, ip for 1wk). EOS depletion and IL-33 neutralization studies were performed by ip administration (2X/wk for 6 wks) of Abs against IL-5/CCR3 and anti-ST2 (all 5mg/kg), respectively, on inflamed SAMP, and ileitis and cytokine expression evaluated. Results: Ileal IL-33, IL-5, and eotaxin-1 & -2 mRNA transcripts increased according to disease severity in SAMP (4- vs. 20-wk-old, p<0.01) and were elevated vs. age-matched AKR controls (p<0.05). EOS infiltration showed a similar trend with more abundant and intense MBP staining in cells morphologically resembling EOS during disease progression in SAMP, and was virtually absent in AKR. Administration of rIL-33 induced an increase in the Th2 cytokines, IL-4, -5, &-10, levels in MLN of treated vs. vehicle-treated mice (p<0.05). Lastly, administration of either anti-IL-5/anti-CCR3 or antiST2 to inflamed SAMP resulted in a marked decrease in ileal inflammation (p<0.01), EOS infiltration, and Th2 cytokine/eotaxin-1&-2 mRNA expression (p<0.01) vs. IgG control-treated mice. Conclusions: Taken together, these data demonstrate a pathogenic role of IL33-mediated EOS infiltration and function in chronic intestinal inflammation, and that blockade of IL-33 and/or downstream EOS activation may represent a novel therapeutic modality to treat patients with IBD.
P.05.3 COMPLEX PERIANAL CROHN’S DISEASE: EFFECTIVENESS OF COMBINED SETON PLACEMENT AND ANTI-TNF ALPHA AGENTS IN MONOTHERAPY OR IN ASSOCIATION WITH IMMUNOSUPPRESSANTS A. Armuzzi 1 , M. Marzo ∗ ,1 , C. Felice 1 , D. Pugliese 1 , G. Andrisani 1 , A. Parello 2 , I. De Vitis 1 , G.L. Rapaccini 1 , A. Papa 1 , C. Ratto 2 , L. Guidi 1 1 Uoc Medicina Interna e Gastroenterologia, Complesso Integrato Columbus, Università Cattolica, Roma, Italy; 2 Uoc Chirurgia Digestiva, Policlinico Gemelli, Università Cattolica, Roma, Italy
Background and aim: Complex perianal fistulas are a very disabling manifestation and source of morbidity for Crohn’s disease (CD) patients. In the last years, the introduction of anti-TNF agents has strongly modified the management of perianal CD. A comprehensive strategy with medical and surgical approach is required to optimize treatment in this group of patients. The aim of this study was to evaluate the clinical effectiveness of combined seton placement and treatment with biologics in monotherapy or in association with immunosuppressive agents in patients with complex perianal CD. Material and methods: Consecutive patients with complex perianal CD, all naïve to biologics and immunosuppressants, were studied. Perianal sepsis was treated with antibiotics and surgically eradicated when necessary. All patients underwent baseline transanal endoscopic ultrasound (EUS) and/or pelvic magnetic resonance imaging (MRI). Setons were then placed in all patients before starting anti-TNF alpha therapy. The presence of fistula healing
on perianal imaging was used to guide seton removal. Fistula healing was defined using both clinical and imaging evaluation. Results: Forty-nine patients were included. Infliximab was administered to 37 patients and Adalimumab to 8 patients, 4 patients received both drugs consecutively. Thirty-three patients received only anti-TNF alpha therapy, whereas 16 patients were treated in combination with immunomodulators. Fistula healing was achieved in 25 of 49 patients (51%) after a median time of 10 months (range 2-24). The median time under anti-TNF alpha therapy was 16 months (range 2-98). Setons were removed after a median time of 8 months (95% CI 5-11). Patients treated with combination therapy of biologics and immunosuppressors achieved a significantly higher fistula healing rate with respect to patients treated with anti-TNF alpha alone (87% vs 33%; p=0.0005). Conclusions: A combined approach with seton placement and biological therapy with anti-TNF alpha agents showed high efficacy in the management of patients with complex perianal CD. The association between anti-TNF alpha and immunosuppressive agents seems to be more effective as compared to biological monotherapy.
P.05.4 ARTERIAL STIFFNESS IS INCREASED IN IBD PATIENTS G. Inserra ∗ , L. Zanoli, M.R. Cannavò, L. Samperi, P. Castellino Medicina Interna, Azienda Policlinico, Catania, Italy Background and aim: Recent studies have reported early atherosclerosis in patients with inflammatory bowel disease (IBD). In these patients, the chronic low grade inflammation may predispose to vascular remodelling and arterial stiffening. We aimed at studying arterial stiffness in IBD patients. Material and methods: 32 IBD patients without cardiovascular risk factors and 32 matched controls were enrolled (age 19-49 years). SphygmoCor device (AtCor Medical) was used to measure carotid-femoral and carotid-radial (muscular artery) pulse wave velocity (PWV), augmentation index, and central blood pressure. Results: Carotid-femoral PWV was higher in IBD patients than in controls (6.6±1.4 m/s vs. 6.0±0.8, respectively, P<0.05), as well as carotid-radial PWV (8.5±1.2 m/s vs. 7.2±1.0, P<0.001). Central pulse pressure was higher in IBD than in controls (32±6 mm Hg vs. 28±7 mm Hg, P<0.05). Aging was an important determinant of carotid-femoral PWV in both groups and carotid-radial PWV only in IBD patients. In fully adjusted model performed in both groups of patients considered as a whole, age was positively associated with carotid-femoral PWV (R2=0.10; +0.05 m/s per 1 year of aging, 95% CI 0.01-0.08 m/s, P<0.05), as well as IBD (R2=0.10; +0.72 m/s if IBD present, 95% CI 0.19-1.26 m/s, P<0.05). In IBD patients, carotid-radial PWV was positively associated with the disease duration (R2=0.20; +0.11 m/s per 1 year of aging, 95% CI 0.03-0.19 m/s, P<0.05). Conclusions: Arterial stiffness is increased in patients with IBD independently of conventional cardiovascular risk factors.
P.05.5 PREDICTIVE FACTORS OF ONE-YEAR MUCOSAL HEALING IN A COHORT OF ULCERATIVE COLITIS PATIENTS TREATED WITH INFLIXIMAB A. Papa ∗ ,1 , G. Andrisani 1 , I. De Vitis 1 , C. Felice 1 , M. Marzo 1 , G. Mocci 1 , D. Pugliese 1 , L. Guidi 1 , A. Armuzzi 1 , A. Gasbarrini 2 , G.L. Rapaccini 1 1 Università Cattolica Del S. Cuore, C.I. Columbus, U.O. Medicina Interna e Gastroenterologia, Roma, Italy; 2 Università Cattolica Del S. Cuore, Policlinico A. Gemelli, U.O. Medicina Interna e Gastroenterologia, Roma, Italy
Background and aim: Recent studies have shown that in patients with ulcerative colitis (UC) the mucosal healing (MH) is a reliable marker of response to biological therapy with important prognostic implications, including longterm remission and colectomy-rate. However, the factors that determine the achievement of the MH in UC patients treated with the anti-TNF-a agent infliximab (IFX) are poorly defined.
Abstracts of the 18th National Congress of Digestive Diseases / Digestive and Liver Disease 44S (2012) S55–S220
P.05.2 PATHOGENIC ROLE OF IL-33-MEDIATED EOS INFILTRATION AND FUNCTION IN EXPERIMENTAL INFLAMMATORY BOWEL DISEASE C. De Salvo ∗ ,1 , X.M. Wang 1 , B. Mattioli 1 , L. Pastorelli 1 , R. Garg 1 , S. Chowhdry 1 , W. Xin 1 , M. Vecchi 2 , T. Pizarro 1 1 Case
Western Reserve University, Cleveland, Oh, United States; 2 Irccs Policlinico San Donato, San Donato Milanese (Mi), Italy Background and aim: IL-33, a new member of the IL-1 family, is linked to several immune and inflammatory disorders, such as IBD. Eosinophils (EOS) are found in active inflammatory lesions of IBD patients and can secrete proinflammatory molecules, alter epithelial barrier function and initiate mucosal immune responses leading to chronic gut inflammation. Recent evidence show that IL-33 can regulate EOS infiltration and function. The aim of this study is to determine IL-33-mediated EOS activation and ileal inflammation in the SAMP1/YitFc (SAMP) murine model of chronic enteritis. Material and methods: EOS were detected by IHC for major basic protein (MBP). IL-33 and EOS-associated cytokines, IL-5 and eotaxin-1,-2,-3, were measured by qPCR in a timecourse study of SAMP and AKR (parental control) ilea. Th2 cytokines were measured by ELISA in mesenteric lymph nodes (MLN) of SAMP treated daily with rIL-33 (33 ug/kg, ip for 1wk). EOS depletion and IL-33 neutralization studies were performed by ip administration (2X/wk for 6 wks) of Abs against IL-5/CCR3 and anti-ST2 (all 5mg/kg), respectively, on inflamed SAMP, and ileitis and cytokine expression evaluated. Results: Ileal IL-33, IL-5, and eotaxin-1 & -2 mRNA transcripts increased according to disease severity in SAMP (4- vs. 20-wk-old, p<0.01) and were elevated vs. age-matched AKR controls (p<0.05). EOS infiltration showed a similar trend with more abundant and intense MBP staining in cells morphologically resembling EOS during disease progression in SAMP, and was virtually absent in AKR. Administration of rIL-33 induced an increase in the Th2 cytokines, IL-4, -5, &-10, levels in MLN of treated vs. vehicle-treated mice (p<0.05). Lastly, administration of either anti-IL-5/anti-CCR3 or antiST2 to inflamed SAMP resulted in a marked decrease in ileal inflammation (p<0.01), EOS infiltration, and Th2 cytokine/eotaxin-1&-2 mRNA expression (p<0.01) vs. IgG control-treated mice. Conclusions: Taken together, these data demonstrate a pathogenic role of IL33-mediated EOS infiltration and function in chronic intestinal inflammation, and that blockade of IL-33 and/or downstream EOS activation may represent a novel therapeutic modality to treat patients with IBD.
P.05.3 COMPLEX PERIANAL CROHN’S DISEASE: EFFECTIVENESS OF COMBINED SETON PLACEMENT AND ANTI-TNF ALPHA AGENTS IN MONOTHERAPY OR IN ASSOCIATION WITH IMMUNOSUPPRESSANTS A. Armuzzi 1 , M. Marzo ∗ ,1 , C. Felice 1 , D. Pugliese 1 , G. Andrisani 1 , A. Parello 2 , I. De Vitis 1 , G.L. Rapaccini 1 , A. Papa 1 , C. Ratto 2 , L. Guidi 1 1 Uoc Medicina Interna e Gastroenterologia, Complesso Integrato Columbus, Università Cattolica, Roma, Italy; 2 Uoc Chirurgia Digestiva, Policlinico Gemelli, Università Cattolica, Roma, Italy
Background and aim: Complex perianal fistulas are a very disabling manifestation and source of morbidity for Crohn’s disease (CD) patients. In the last years, the introduction of anti-TNF agents has strongly modified the management of perianal CD. A comprehensive strategy with medical and surgical approach is required to optimize treatment in this group of patients. The aim of this study was to evaluate the clinical effectiveness of combined seton placement and treatment with biologics in monotherapy or in association with immunosuppressive agents in patients with complex perianal CD. Material and methods: Consecutive patients with complex perianal CD, all naïve to biologics and immunosuppressants, were studied. Perianal sepsis was treated with antibiotics and surgically eradicated when necessary. All patients underwent baseline transanal endoscopic ultrasound (EUS) and/or pelvic magnetic resonance imaging (MRI). Setons were then placed in all patients before starting anti-TNF alpha therapy. The presence of fistula healing
on perianal imaging was used to guide seton removal. Fistula healing was defined using both clinical and imaging evaluation. Results: Forty-nine patients were included. Infliximab was administered to 37 patients and Adalimumab to 8 patients, 4 patients received both drugs consecutively. Thirty-three patients received only anti-TNF alpha therapy, whereas 16 patients were treated in combination with immunomodulators. Fistula healing was achieved in 25 of 49 patients (51%) after a median time of 10 months (range 2-24). The median time under anti-TNF alpha therapy was 16 months (range 2-98). Setons were removed after a median time of 8 months (95% CI 5-11). Patients treated with combination therapy of biologics and immunosuppressors achieved a significantly higher fistula healing rate with respect to patients treated with anti-TNF alpha alone (87% vs 33%; p=0.0005). Conclusions: A combined approach with seton placement and biological therapy with anti-TNF alpha agents showed high efficacy in the management of patients with complex perianal CD. The association between anti-TNF alpha and immunosuppressive agents seems to be more effective as compared to biological monotherapy.
P.05.4 ARTERIAL STIFFNESS IS INCREASED IN IBD PATIENTS G. Inserra ∗ , L. Zanoli, M.R. Cannavò, L. Samperi, P. Castellino Medicina Interna, Azienda Policlinico, Catania, Italy Background and aim: Recent studies have reported early atherosclerosis in patients with inflammatory bowel disease (IBD). In these patients, the chronic low grade inflammation may predispose to vascular remodelling and arterial stiffening. We aimed at studying arterial stiffness in IBD patients. Material and methods: 32 IBD patients without cardiovascular risk factors and 32 matched controls were enrolled (age 19-49 years). SphygmoCor device (AtCor Medical) was used to measure carotid-femoral and carotid-radial (muscular artery) pulse wave velocity (PWV), augmentation index, and central blood pressure. Results: Carotid-femoral PWV was higher in IBD patients than in controls (6.6±1.4 m/s vs. 6.0±0.8, respectively, P<0.05), as well as carotid-radial PWV (8.5±1.2 m/s vs. 7.2±1.0, P<0.001). Central pulse pressure was higher in IBD than in controls (32±6 mm Hg vs. 28±7 mm Hg, P<0.05). Aging was an important determinant of carotid-femoral PWV in both groups and carotid-radial PWV only in IBD patients. In fully adjusted model performed in both groups of patients considered as a whole, age was positively associated with carotid-femoral PWV (R2=0.10; +0.05 m/s per 1 year of aging, 95% CI 0.01-0.08 m/s, P<0.05), as well as IBD (R2=0.10; +0.72 m/s if IBD present, 95% CI 0.19-1.26 m/s, P<0.05). In IBD patients, carotid-radial PWV was positively associated with the disease duration (R2=0.20; +0.11 m/s per 1 year of aging, 95% CI 0.03-0.19 m/s, P<0.05). Conclusions: Arterial stiffness is increased in patients with IBD independently of conventional cardiovascular risk factors.
P.05.5 PREDICTIVE FACTORS OF ONE-YEAR MUCOSAL HEALING IN A COHORT OF ULCERATIVE COLITIS PATIENTS TREATED WITH INFLIXIMAB A. Papa ∗ ,1 , G. Andrisani 1 , I. De Vitis 1 , C. Felice 1 , M. Marzo 1 , G. Mocci 1 , D. Pugliese 1 , L. Guidi 1 , A. Armuzzi 1 , A. Gasbarrini 2 , G.L. Rapaccini 1 1 Università Cattolica Del S. Cuore, C.I. Columbus, U.O. Medicina Interna e Gastroenterologia, Roma, Italy; 2 Università Cattolica Del S. Cuore, Policlinico A. Gemelli, U.O. Medicina Interna e Gastroenterologia, Roma, Italy
Background and aim: Recent studies have shown that in patients with ulcerative colitis (UC) the mucosal healing (MH) is a reliable marker of response to biological therapy with important prognostic implications, including longterm remission and colectomy-rate. However, the factors that determine the achievement of the MH in UC patients treated with the anti-TNF-a agent infliximab (IFX) are poorly defined.