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Tu1226 Anti-TNF Agents are Changing the Natural History of Crohn's Disease
Tu1227 Treatment of Refractory Crohn's Disease With Allogeneic, Bone MarrowDerived Adult Mesenchymal Stromal Cells Renate Schmelz, Stefan Brueckner, Jana Babatz, Katja Richter, Nadine Muench, Kristina Hoelig, Mathias Krech, Martin Bornhäuser Objectives: Crohn's disease is characterized as a life-long, chronic inflammatory bowel disease with pathologic T-cell response which can occur in every part of the gastrointestinal tract. An imbalance in local mucosal production of pro-inflammatory cytokines over anti-inflammatory cytokines is theorized to cause the well-demarcated, discontinuous, transmural, ulcerative lesions characteristic of the disease. Some patients present as treatment-refractory Crohn's disease with poor clinical outcome. Mesenchymal stromal cells (MSC) can affect an adaptive immune response by exerting their immunoregulative effects through direct interaction with T-cells and blocking of TNF-alpha. These immunoregulatory effects mainly occur in a localized tissue environment and have limited systemic consequences. Methods: During 06/ 2009 until 04/2011 seven patients (n= 4 female) with refractory Crohn's disease (n=4: ileostoma with peristomal ulcer and/or fistula, n=1: intrapyloric ulcer, n= 1: inflammatory stenosis of the rectum, n=1: CDAI 308) were treated with MSCs. Bone-marrow derived MSCs from unrelated HLA disparate donors were expanded in platelet lysate containing medium and characterized by their morphological, phenotypical and functional properties. An intravenous application of MSCs ranging from 0.94*10^6 cells/kg to 2.01*10^6 cells/ kg respectively was performed at day 1 and 4. Results: Two patients (29%) showed a complete response of their fistulas and/ or ulcers in the para-ileostomal region. One patient had partial response with complete closure of the peristomal ulcers, but no effect on his enterocutaneous fistula. Four patients represented without any significant treatment response. One male showed an allergic reaction according to DMSO during the first application of MSCs, the second application was tolerated very well. No other side effects occurred. Conclusion: MSCs should be considered as a therapeutic option in patients who have failed to respond to standard treatment. Response rate in our case series was 29%. Particularly patients with peristomal problems e.g. fistulas und ulcers seem to profit. MSC-based treatment is well tolerated and a potent therapy which should be confirmed in controlled studies. Still it remains very interesting if higher doses of MSCs could achieve increased response rates.
SROC curve revealing moderate diagnostic accuracy of PAB for the diagnosis of IBD Tu1225 Upper Gastrointestinal Tract Involvement in Crohn's Disease Requiring AntiTNF Therapy: Clinical Characteristics William J. Tremaine, William A. Faubion, Darrell S. Pardi, Lawrence J. Timmons, Sunanda V. Kane, Edward V. Loftus Crohn's disease of the upper GI tract has been reported to be associated with more severe disease compared to lower GI involvement alone. Aim: To determine the clinical features of patients (pts) with Crohn's disease with upper GI tract involvement with severe disease as indicated by the need for anti-TNF alpha therapy. Methods: The medical records of pts with upper GI tract Crohn's disease seen at a tertiary care center between January 1, 1999 and December 31, 2009 were reviewed and those treated with an anti-TNF biologic were included. Results: We confirmed 410 patients with Crohn's disease with upper GI tract involvement including 33 treated with biologics (infliximab 22; adalimumab 5; multiple biologics 5; certolizumab pegol 1). There were 21 females (64%). Median age was 33 years (range, 12-62). Five pts had a family history of IBD. Six pts were current smokers at the start of biologic therapy. Upper GI symptoms were predominant in only 9 pts (28%) and 7 of the 9 pts (78%) had symptom relief with biologic treatment. One pt had gastric Crohn's disease without distal involvement; 30 pts also had ileal and/or colonic disease and two pts had perianal disease without ileal or colonic disease. Altogether, sixteen pts (48%) had perianal disease. Granulomas were identified in 10 pts (30%). Seventeen pts (52%) had previous surgery for Crohn's disease. A total of ten pts had a complete clinical response, 10 pts had a partial clinical response, and 13 pts had no response. Ten pts (30%) had severe adverse reactions to biologics requiring discontinuation of therapy, including: dermatitis 3; infections 2; delayed hypersensitivity reactions 2; anaphylaxis 1; oral lesions 1; and congestive heart failure 1. Conclusions: Lower GI symptoms are the usual indications for biologic therapy in pts with UGI tract Crohn's disease. Only one pt had isolated upper GI tract Crohn's disease. Granulomas were found in about a third of patients with UGI Crohn's treated with biologics. Nearly half of patients with upper GI Crohn's disease requiring biologics had perianal disease. Most patients with symptomatic upper GI Crohn's disease improved with biologic therapy, but more than one out of four pts had severe complications from therapy.
Tu1228 Disparity in Clinical Care for Patients With Inflammatory Bowel Disease Between Specialists and Non-Specialists Tomoko Hirakawa, Jun Kato, Sakuma Takahashi, Hideyuki Suzuki, Mitsuhiro Akita, Shunsuke Saito, Eisuke Kaji, Sakiko Hiraoka, Hiroyuki Okada, Kazuhide Yamamoto BACKGROUND: Although inflammatory bowel disease (IBD) patients have been increasing and new therapeutic options for IBD have developed, doctors who specialize in IBD are relatively few. Patients treated by a non-specialist of IBD may not receive appropriate treatment. The aim of this study is to clarify importance of expertise in IBD by comparing disease and medication status between IBD patients treated by an IBD specialist and those treated by an IBD non-specialist. METHODS: Medical charts of ambulating IBD patients in two hospitals at the same time point (November 2010) were examined. All patients in one hospital were treated by one of IBD specialists, while in the other, patients were treated by one of gastroenterologists of non-specialist of IBD. RESULTS: The numbers of IBD patients were 255 (hospital with specialists) and 74 (hospital without specialists), respectively. Extensive colitis, left-sided colitis, and proctitis were nearly evenly distributed in ulcerative colitis (UC) patients of the hospital with specialists, while approximately two thirds of UC patients in the hospital without specialists were extensive colitis (p = 0.0007). Disease activity was not well-controlled in the patients of the hospital without specialists compared to in the patients of the hospital with specialists (remission or mild activity; UC: 93% vs. 77%, p = 0.0006 and Crohn's disease (CD): 85% vs. 62%, p = 0.012, respectively). 5-ASA agents were not sufficiently utilized for patients in the hospital without specialists. For example, the proportion of patients using salazosulfapyridine was significantly higher in UC patients of the hospital with specialists than in UC patients of the hospital without specialists (30% vs. 7%, p = 0.0022). On the other hand, the proportion of UC patients who received insufficient dose of mesalazine (Pentasa < 3 g/day or Asacol < 3.6 g/day) was significantly higher in the hospital without specialsits (47% vs. 15%, p < .0001). Moreover, topical therapy was less frequently used for UC patients in the hospital without specialists (2% vs. 17%, p = 0.013). In the hospital without specialists, significantly more patients received long-term (more than 6 months) oral corticosteroids (UC: 23% vs. 5%, p < .0001, CD: 23% vs. 4%, p = 0.012, respectively), while significantly fewer patients received immunomodulators (azathioprine or mercaptopurine) (UC + CD; 14% vs. 44%, p < .0001). Biologics use in CD was more familiar in the hospital with specialists (46% vs. 15%, p = 0.0083). CONCLUSION: IBD patients of the hospital without specialists were not well-controlled and were not prescribed therapeutic drugs appropriately. Fostering and placement of the specialists of IBD is an urgent problem for disseminating appropriate IBD treatment.
Tu1226 Anti-TNF Agents are Changing the Natural History of Crohn's Disease Yi - Tzu Nancy Fu, Thomas Hong, Hong Qian, Brian Bressler Background: Anti-TNF agents have been available for treating patients with Crohn's disease (CD) for over a decade. However, it is still unclear whether these agents significantly impact the natural progression of CD. Aim: We investigated the difference in patient phenotype, time from disease diagnosis to surgery, medication usage and amount of small bowel resected in patients with CD undergoing their first surgical resection between 1995-2000 and 20052010. Methods: We retrospectively evaluated all patients with CD undergoing their first surgical resections between 1995-2000 and 2005-2010 at a tertiary care hospital (St. Paul's Hospital, Vancouver, Canada). Patients were identified using ICD 9/10 diagnostic codes and their electronic records were reviewed. For statistical analysis, chi-square tests were performed for categorical variables, and t tests or Wilcoxon rank-sum were used for continuous variables. Results: There were 85 and 114 CD patients who had surgical resection between 19952000 and 2005-2010, respectively. Compared to 1995-2000, the 2005-2010 cohort had more patients that were male (1995-2000 vs. 2005-2010; 30.6% vs. 54.4%, p=0.001) and on immunosupressants (21.4% vs. 56.1%, p<0.0001), but less on 5-aminosalysilic acid (53.6% vs. 29.8%, p=0.001). Thirty eight patients (33.3%) received anti-TNF agents in the later cohort, no patient received anti-TNF agents in the earlier cohort. Based on the Montreal classification, patients requiring surgery had significantly different disease behaviour (B1/ B2/B3 38.8%/31.8%/29.4% vs. 12.3%/45.6%/42.1%, p<0.0001) and disease location (L1/ L2/L3 32.9%/28.2%/38.8% vs. 26.3%/14.9%/58.8%, p=0.01). Both groups had similar median age, time from diagnosis to surgery, amount of small bowel resected, corticosteroid use, and post-operative complications. Within the 2005-2010 cohort, 38 patients (33.3%) received anti-TNF agents. Compared to patients not on anti-TNF agents, these patients had similar disease behaviour, but significantly different age at diagnosis (No anti-TNF agents
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vs. anti-TNF agents; A1/A2/A3 11.8%/73.7%/14.5% vs. 39.5%/50%/10.5%, p=0.003) and disease location (L1/L2/L3 27.6%/7.9%/64.5% vs. 23.7%/29%/47.4%, p=0.01). Significantly shorter median time from diagnosis to surgery was observed in patients not receiving antiTNF agents (48 vs. 90 months, p=0.02). Interestingly, this was shorter than the 72-month median time for the 1995-2000 cohort; suggesting an overall sicker patient population in the 2005-2010 cohort. Conclusions: Significantly different patient phenotype and medication usage were observed in the anti-TNF versus pre-anti-TNF era. Patients on anti-TNF agents had longer time from disease diagnosis to their first surgical resection. Anti-TNF agents are changing the natural history of Crohn's disease.
SROC curve revealing moderate diagnostic accuracy of PAB for the diagnosis of IBD Tu1225 Upper Gastrointestinal Tract Involvement in Crohn's Disease Requiring AntiTNF Therapy: Clinical Characteristics William J. Tremaine, William A. Faubion, Darrell S. Pardi, Lawrence J. Timmons, Sunanda V. Kane, Edward V. Loftus Crohn's disease of the upper GI tract has been reported to be associated with more severe disease compared to lower GI involvement alone. Aim: To determine the clinical features of patients (pts) with Crohn's disease with upper GI tract involvement with severe disease as indicated by the need for anti-TNF alpha therapy. Methods: The medical records of pts with upper GI tract Crohn's disease seen at a tertiary care center between January 1, 1999 and December 31, 2009 were reviewed and those treated with an anti-TNF biologic were included. Results: We confirmed 410 patients with Crohn's disease with upper GI tract involvement including 33 treated with biologics (infliximab 22; adalimumab 5; multiple biologics 5; certolizumab pegol 1). There were 21 females (64%). Median age was 33 years (range, 12-62). Five pts had a family history of IBD. Six pts were current smokers at the start of biologic therapy. Upper GI symptoms were predominant in only 9 pts (28%) and 7 of the 9 pts (78%) had symptom relief with biologic treatment. One pt had gastric Crohn's disease without distal involvement; 30 pts also had ileal and/or colonic disease and two pts had perianal disease without ileal or colonic disease. Altogether, sixteen pts (48%) had perianal disease. Granulomas were identified in 10 pts (30%). Seventeen pts (52%) had previous surgery for Crohn's disease. A total of ten pts had a complete clinical response, 10 pts had a partial clinical response, and 13 pts had no response. Ten pts (30%) had severe adverse reactions to biologics requiring discontinuation of therapy, including: dermatitis 3; infections 2; delayed hypersensitivity reactions 2; anaphylaxis 1; oral lesions 1; and congestive heart failure 1. Conclusions: Lower GI symptoms are the usual indications for biologic therapy in pts with UGI tract Crohn's disease. Only one pt had isolated upper GI tract Crohn's disease. Granulomas were found in about a third of patients with UGI Crohn's treated with biologics. Nearly half of patients with upper GI Crohn's disease requiring biologics had perianal disease. Most patients with symptomatic upper GI Crohn's disease improved with biologic therapy, but more than one out of four pts had severe complications from therapy.
Tu1228 Disparity in Clinical Care for Patients With Inflammatory Bowel Disease Between Specialists and Non-Specialists Tomoko Hirakawa, Jun Kato, Sakuma Takahashi, Hideyuki Suzuki, Mitsuhiro Akita, Shunsuke Saito, Eisuke Kaji, Sakiko Hiraoka, Hiroyuki Okada, Kazuhide Yamamoto BACKGROUND: Although inflammatory bowel disease (IBD) patients have been increasing and new therapeutic options for IBD have developed, doctors who specialize in IBD are relatively few. Patients treated by a non-specialist of IBD may not receive appropriate treatment. The aim of this study is to clarify importance of expertise in IBD by comparing disease and medication status between IBD patients treated by an IBD specialist and those treated by an IBD non-specialist. METHODS: Medical charts of ambulating IBD patients in two hospitals at the same time point (November 2010) were examined. All patients in one hospital were treated by one of IBD specialists, while in the other, patients were treated by one of gastroenterologists of non-specialist of IBD. RESULTS: The numbers of IBD patients were 255 (hospital with specialists) and 74 (hospital without specialists), respectively. Extensive colitis, left-sided colitis, and proctitis were nearly evenly distributed in ulcerative colitis (UC) patients of the hospital with specialists, while approximately two thirds of UC patients in the hospital without specialists were extensive colitis (p = 0.0007). Disease activity was not well-controlled in the patients of the hospital without specialists compared to in the patients of the hospital with specialists (remission or mild activity; UC: 93% vs. 77%, p = 0.0006 and Crohn's disease (CD): 85% vs. 62%, p = 0.012, respectively). 5-ASA agents were not sufficiently utilized for patients in the hospital without specialists. For example, the proportion of patients using salazosulfapyridine was significantly higher in UC patients of the hospital with specialists than in UC patients of the hospital without specialists (30% vs. 7%, p = 0.0022). On the other hand, the proportion of UC patients who received insufficient dose of mesalazine (Pentasa < 3 g/day or Asacol < 3.6 g/day) was significantly higher in the hospital without specialsits (47% vs. 15%, p < .0001). Moreover, topical therapy was less frequently used for UC patients in the hospital without specialists (2% vs. 17%, p = 0.013). In the hospital without specialists, significantly more patients received long-term (more than 6 months) oral corticosteroids (UC: 23% vs. 5%, p < .0001, CD: 23% vs. 4%, p = 0.012, respectively), while significantly fewer patients received immunomodulators (azathioprine or mercaptopurine) (UC + CD; 14% vs. 44%, p < .0001). Biologics use in CD was more familiar in the hospital with specialists (46% vs. 15%, p = 0.0083). CONCLUSION: IBD patients of the hospital without specialists were not well-controlled and were not prescribed therapeutic drugs appropriately. Fostering and placement of the specialists of IBD is an urgent problem for disseminating appropriate IBD treatment.
Tu1226 Anti-TNF Agents are Changing the Natural History of Crohn's Disease Yi - Tzu Nancy Fu, Thomas Hong, Hong Qian, Brian Bressler Background: Anti-TNF agents have been available for treating patients with Crohn's disease (CD) for over a decade. However, it is still unclear whether these agents significantly impact the natural progression of CD. Aim: We investigated the difference in patient phenotype, time from disease diagnosis to surgery, medication usage and amount of small bowel resected in patients with CD undergoing their first surgical resection between 1995-2000 and 20052010. Methods: We retrospectively evaluated all patients with CD undergoing their first surgical resections between 1995-2000 and 2005-2010 at a tertiary care hospital (St. Paul's Hospital, Vancouver, Canada). Patients were identified using ICD 9/10 diagnostic codes and their electronic records were reviewed. For statistical analysis, chi-square tests were performed for categorical variables, and t tests or Wilcoxon rank-sum were used for continuous variables. Results: There were 85 and 114 CD patients who had surgical resection between 19952000 and 2005-2010, respectively. Compared to 1995-2000, the 2005-2010 cohort had more patients that were male (1995-2000 vs. 2005-2010; 30.6% vs. 54.4%, p=0.001) and on immunosupressants (21.4% vs. 56.1%, p<0.0001), but less on 5-aminosalysilic acid (53.6% vs. 29.8%, p=0.001). Thirty eight patients (33.3%) received anti-TNF agents in the later cohort, no patient received anti-TNF agents in the earlier cohort. Based on the Montreal classification, patients requiring surgery had significantly different disease behaviour (B1/ B2/B3 38.8%/31.8%/29.4% vs. 12.3%/45.6%/42.1%, p<0.0001) and disease location (L1/ L2/L3 32.9%/28.2%/38.8% vs. 26.3%/14.9%/58.8%, p=0.01). Both groups had similar median age, time from diagnosis to surgery, amount of small bowel resected, corticosteroid use, and post-operative complications. Within the 2005-2010 cohort, 38 patients (33.3%) received anti-TNF agents. Compared to patients not on anti-TNF agents, these patients had similar disease behaviour, but significantly different age at diagnosis (No anti-TNF agents
S-779
AGA Abstracts
AGA Abstracts
vs. anti-TNF agents; A1/A2/A3 11.8%/73.7%/14.5% vs. 39.5%/50%/10.5%, p=0.003) and disease location (L1/L2/L3 27.6%/7.9%/64.5% vs. 23.7%/29%/47.4%, p=0.01). Significantly shorter median time from diagnosis to surgery was observed in patients not receiving antiTNF agents (48 vs. 90 months, p=0.02). Interestingly, this was shorter than the 72-month median time for the 1995-2000 cohort; suggesting an overall sicker patient population in the 2005-2010 cohort. Conclusions: Significantly different patient phenotype and medication usage were observed in the anti-TNF versus pre-anti-TNF era. Patients on anti-TNF agents had longer time from disease diagnosis to their first surgical resection. Anti-TNF agents are changing the natural history of Crohn's disease.