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PA.168 MUCOSAL HEALING IN ULCERATIVE COLITIS PATIENTS IN LONG-TERM TREATMENT WITH INFLIXIMAB
Abstracts / Digestive and Liver Disease 40S (2008), S1–S195 PA.168 MUCOSAL HEALING IN ULCERATIVE COLITIS PATIENTS IN LONG-TERM TREATMENT WITH INFLIXIMAB A. Papa ∗ ,1 , I. De Vitis 1 , S. Guglielmo 1 , A. Tursi 2 , G. Brandimarte 3 , W. Elisei 3 , I. Roberto 1 , S. Ennas 1 , G. Mocci 1 , M. Bonizzi 1 , C. Felice 1 , G. Andrisani 1 , L. Guidi 1 , A. Gasbarrini 1 , G. Fedeli 1 1 Gastroenterologia, 2 Ospedale
Università Cattoica del S. Cuore, Roma; Bonomo, Andria (BA); 3 Ospedale Cristo Re, Roma
Background and aim: Infliximab has shown clinical and endoscopic efficacy in short-term therapy in patients with moderate-to-severe steroid-resistant or steroid dependent ulcerative colitis (UC). However, data on mucosal healing in UC patients with long-term scheduled maintenance therapy are scarce. Aim of this study was to assess the long-term efficacy of infliximab on endoscopic activity in UC patients. Material and methods: Seventeen patients with moderate-to-severe active UC (l5 steroid dependent and 2 steroid-resistant) were investigated. All patients were clinical responder to the infliximab induction course and underwent to a scheduled (every 8 weeks) maintenance therapy at the same dosage. Colonoscopy was performed at baseline and at week 54 (±8) or in case of clinical relapse. In 3 patients colonoscopy was performed also after 110 (±8) weeks. Clinical activity was assessed by Mayo score (scores can range from 0 to 12, with higher scores indicating more severe disease) and endoscopic activity was measured by means of Mayo subscore for endoscopy (0= normal or inactive disease, 1= mild disease, 2= moderate disease, 3= severe disease). Mucosal healing was defined as an absolute subscore for endoscopy of 0 or 1. Results: The total number of infusions was 176, the mean number of infusions for patients was 10.3±3.9. The mean duration of follow-up was 77.3±43.6 weeks. Four patients (23.5%) withdrew from scheduled treatment before one-year follow-up: three underwent to colectomy for loss of response and one had a severe adverse reaction. At enrolment, 15 patients were in treatment with steroids that were gradually tapered and discontinuated, 11 patients were in concomitant treatment with azathioprine, 3 with methotrexate and 3 with 5-ASA. Mean Mayo score was 8.2±1.9 at baseline and 4.2±1.8 at week 54 (±8), with a statistically significant reduction (p=0.04). At enrolment, 10 patients had moderate disease and 7 severe disease at endoscopy, at week 54 (±8) 10/13 (76%) of the remaining patients showed mucosal healing and 3/13 moderate endoscopic activity. The 3 patients that underwent to a second follow-up endoscopy showed persistent clinical and endoscopic remission. Conclusions: Our results demonstrate that long-term scheduled maintenance therapy with infliximab in steroid-resistant and steroid dependent UC patients results in a decreased endoscopic evidence of inflammation with a high rate of persistent mucosal healing. # L. Inflammatory bowel diseases 3. Ulcerative colitis
PA.169 WHICH 5-ASA? VARIATION IN COLONIC MUCOSAL CONCENTRATION OF DIFFERENT PHARMACEUTICAL MESALAMINE FORMULATIONS M. Paccagnella ∗ ,1 , R. D’Incà 1 , R. Cardin 1 , S. Voltan 2 , V. Baldo 3 , G.C. Sturniolo 1 1 Department
of Surgical and Gastroenterological Sciences, Section of Gastroenterology, University of Padua, Padova; 2 Department of Microbiology, University of Padua, Padova; 3 Department of Environmental Medicine and Public Health, Institute of Hygiene, University of Padua, Padova Background and aim: 5-Aminosalicylic acid (5-ASA or mesalamine) represents the mainstay treatment of inflammatory bowel disease (IBD): different pharmaceutical formulations have been developed in order to
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obtain absorption at the site of the disease. Our aim was to evaluate the mucosal concentration of each formulation. Material and methods: 130 consecutive IBD patients receiving oral 5-ASA either pH-dependent release formulations (2.4 g/day) (73 patients), time-dependent release formulations (3 g/day) (11 patients) or pro-drugs (3 g/day) (18 patients),were included in the study. 28 patients received both oral and topical (2-4 g/day enema) of pH-dependent release formulations. Two endoscopic biopsies were taken from the sigmoid colon in each patient undergoing colonoscopy for surveillance or symptom reexacerbation. 5-ASA concentration (ng/mg) was measured in tissue homogenates by high-pressure liquid chromatography with electrochemical detection. Endoscopic and histological disease activity were recorded as remission or active disease. The T-test and Mann-Whitney’s test were used for statistical analysis. Results: pH-dependent release formulations achieved higher mucosal concentrations than prodrugs (51.75±48.88 vs 33.35±24.12,p=0.01) and time-dependent release formulations (38.24±18.37, p=0.04). Furthermore, 28% of the patients under treatment with pH-dependent release formulations had mucosal 5-ASA concentrations above 70 ng/mg of tissue which was the highest concentration achieved with other formulations. Endoscopic remission was associated with significantly higher mucosal 5-ASA concentrations than active disease in patients receiving pH-dependent release formulations (60.14±55.11 vs 35.66±28.44,p=0.02). The same was true for histological assessment (67.53±56.11 vs 35.53±33.80,p<0.001). We found significantly higher mucosal 5ASA concentrations in patients treated both orally and topically than those receiving only oral treatment of pH-dependent release formulation (72.33±59.46 vs 51.75±48.88,p=0.03). Conclusions: Patients with IBD show significant variability in sigmoid mucosal 5-ASA concentration depending on the type of formulation, the highest concentration being obtained with pH-dependent release formulations. Endoscopic and histological activity are inversely related to mucosal concentration of 5-ASA. Higher 5ASA dosages could be therefore justified during active disease in order to obtain better clinical results. # L. Inflammatory bowel diseases 3. Ulcerative colitis
PA.170 ORAL BECLOMETHASONE DIPROPIONATE FOR REDUCING SYSTEMIC COSTICOSTEROIDS REQUIREMENT IN MILD-MODERATE ULCERATIVE COLITIS REFRACTORY TO 5-ASA: SHORT AND LONG TERM OUTCOME A. Aratari ∗ , C. Papi, A. Cossu, M. Tanga, V. Clemente, M. Koch Gastroenterology Unit, S. Filippo Neri Hospital, Roma Background and aim: 5-aminosalicylic acid (5-ASA) is the first-line therapy for mild-moderate ulcerative colitis (UC). According to guidelines, systemic corticosteroids (CS) are used for patients in whom 5-ASA in appropriate dose has been unsuccessful (Carter MJ, Gut 2004). The use of systemic CS is limited by the risk of adverse effects. Beclometasone dipropionate (BMD), a topically acting steroid with low systemic bioavailability has a more favourable safety profile. BMD has been shown to be more effective than 5-ASA alone for inducing remission in mild-moderate UC (Rizzello F, APT 2002) but its role in clinical practice is not well established. The aim of our study was to assess the efficacy of BMD for reducing systemic CS requirement in mild-moderate UC unresponsive to 5-ASA. Material and methods: From 2000 to 2006, patients with mildmoderate UC (Colitis Activity Index, CAI = 5-12) refractory to oral 5-ASA (> 2.4 g/day) + topical 5-ASA and/or topical CS for at least 2 weeks, received a 8 week course of oral BMD (10 mg/day for 4 weeks and 5 mg/day for 4 weeks). Three end-points have been considered: 1) short term remission (CAI < 4 at 8 weeks); 2) prolonged remission (12 months after BMD weaning); 3) reduction of systemic CS requirement.
Università Cattoica del S. Cuore, Roma; Bonomo, Andria (BA); 3 Ospedale Cristo Re, Roma
Background and aim: Infliximab has shown clinical and endoscopic efficacy in short-term therapy in patients with moderate-to-severe steroid-resistant or steroid dependent ulcerative colitis (UC). However, data on mucosal healing in UC patients with long-term scheduled maintenance therapy are scarce. Aim of this study was to assess the long-term efficacy of infliximab on endoscopic activity in UC patients. Material and methods: Seventeen patients with moderate-to-severe active UC (l5 steroid dependent and 2 steroid-resistant) were investigated. All patients were clinical responder to the infliximab induction course and underwent to a scheduled (every 8 weeks) maintenance therapy at the same dosage. Colonoscopy was performed at baseline and at week 54 (±8) or in case of clinical relapse. In 3 patients colonoscopy was performed also after 110 (±8) weeks. Clinical activity was assessed by Mayo score (scores can range from 0 to 12, with higher scores indicating more severe disease) and endoscopic activity was measured by means of Mayo subscore for endoscopy (0= normal or inactive disease, 1= mild disease, 2= moderate disease, 3= severe disease). Mucosal healing was defined as an absolute subscore for endoscopy of 0 or 1. Results: The total number of infusions was 176, the mean number of infusions for patients was 10.3±3.9. The mean duration of follow-up was 77.3±43.6 weeks. Four patients (23.5%) withdrew from scheduled treatment before one-year follow-up: three underwent to colectomy for loss of response and one had a severe adverse reaction. At enrolment, 15 patients were in treatment with steroids that were gradually tapered and discontinuated, 11 patients were in concomitant treatment with azathioprine, 3 with methotrexate and 3 with 5-ASA. Mean Mayo score was 8.2±1.9 at baseline and 4.2±1.8 at week 54 (±8), with a statistically significant reduction (p=0.04). At enrolment, 10 patients had moderate disease and 7 severe disease at endoscopy, at week 54 (±8) 10/13 (76%) of the remaining patients showed mucosal healing and 3/13 moderate endoscopic activity. The 3 patients that underwent to a second follow-up endoscopy showed persistent clinical and endoscopic remission. Conclusions: Our results demonstrate that long-term scheduled maintenance therapy with infliximab in steroid-resistant and steroid dependent UC patients results in a decreased endoscopic evidence of inflammation with a high rate of persistent mucosal healing. # L. Inflammatory bowel diseases 3. Ulcerative colitis
PA.169 WHICH 5-ASA? VARIATION IN COLONIC MUCOSAL CONCENTRATION OF DIFFERENT PHARMACEUTICAL MESALAMINE FORMULATIONS M. Paccagnella ∗ ,1 , R. D’Incà 1 , R. Cardin 1 , S. Voltan 2 , V. Baldo 3 , G.C. Sturniolo 1 1 Department
of Surgical and Gastroenterological Sciences, Section of Gastroenterology, University of Padua, Padova; 2 Department of Microbiology, University of Padua, Padova; 3 Department of Environmental Medicine and Public Health, Institute of Hygiene, University of Padua, Padova Background and aim: 5-Aminosalicylic acid (5-ASA or mesalamine) represents the mainstay treatment of inflammatory bowel disease (IBD): different pharmaceutical formulations have been developed in order to
S137
obtain absorption at the site of the disease. Our aim was to evaluate the mucosal concentration of each formulation. Material and methods: 130 consecutive IBD patients receiving oral 5-ASA either pH-dependent release formulations (2.4 g/day) (73 patients), time-dependent release formulations (3 g/day) (11 patients) or pro-drugs (3 g/day) (18 patients),were included in the study. 28 patients received both oral and topical (2-4 g/day enema) of pH-dependent release formulations. Two endoscopic biopsies were taken from the sigmoid colon in each patient undergoing colonoscopy for surveillance or symptom reexacerbation. 5-ASA concentration (ng/mg) was measured in tissue homogenates by high-pressure liquid chromatography with electrochemical detection. Endoscopic and histological disease activity were recorded as remission or active disease. The T-test and Mann-Whitney’s test were used for statistical analysis. Results: pH-dependent release formulations achieved higher mucosal concentrations than prodrugs (51.75±48.88 vs 33.35±24.12,p=0.01) and time-dependent release formulations (38.24±18.37, p=0.04). Furthermore, 28% of the patients under treatment with pH-dependent release formulations had mucosal 5-ASA concentrations above 70 ng/mg of tissue which was the highest concentration achieved with other formulations. Endoscopic remission was associated with significantly higher mucosal 5-ASA concentrations than active disease in patients receiving pH-dependent release formulations (60.14±55.11 vs 35.66±28.44,p=0.02). The same was true for histological assessment (67.53±56.11 vs 35.53±33.80,p<0.001). We found significantly higher mucosal 5ASA concentrations in patients treated both orally and topically than those receiving only oral treatment of pH-dependent release formulation (72.33±59.46 vs 51.75±48.88,p=0.03). Conclusions: Patients with IBD show significant variability in sigmoid mucosal 5-ASA concentration depending on the type of formulation, the highest concentration being obtained with pH-dependent release formulations. Endoscopic and histological activity are inversely related to mucosal concentration of 5-ASA. Higher 5ASA dosages could be therefore justified during active disease in order to obtain better clinical results. # L. Inflammatory bowel diseases 3. Ulcerative colitis
PA.170 ORAL BECLOMETHASONE DIPROPIONATE FOR REDUCING SYSTEMIC COSTICOSTEROIDS REQUIREMENT IN MILD-MODERATE ULCERATIVE COLITIS REFRACTORY TO 5-ASA: SHORT AND LONG TERM OUTCOME A. Aratari ∗ , C. Papi, A. Cossu, M. Tanga, V. Clemente, M. Koch Gastroenterology Unit, S. Filippo Neri Hospital, Roma Background and aim: 5-aminosalicylic acid (5-ASA) is the first-line therapy for mild-moderate ulcerative colitis (UC). According to guidelines, systemic corticosteroids (CS) are used for patients in whom 5-ASA in appropriate dose has been unsuccessful (Carter MJ, Gut 2004). The use of systemic CS is limited by the risk of adverse effects. Beclometasone dipropionate (BMD), a topically acting steroid with low systemic bioavailability has a more favourable safety profile. BMD has been shown to be more effective than 5-ASA alone for inducing remission in mild-moderate UC (Rizzello F, APT 2002) but its role in clinical practice is not well established. The aim of our study was to assess the efficacy of BMD for reducing systemic CS requirement in mild-moderate UC unresponsive to 5-ASA. Material and methods: From 2000 to 2006, patients with mildmoderate UC (Colitis Activity Index, CAI = 5-12) refractory to oral 5-ASA (> 2.4 g/day) + topical 5-ASA and/or topical CS for at least 2 weeks, received a 8 week course of oral BMD (10 mg/day for 4 weeks and 5 mg/day for 4 weeks). Three end-points have been considered: 1) short term remission (CAI < 4 at 8 weeks); 2) prolonged remission (12 months after BMD weaning); 3) reduction of systemic CS requirement.