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Observations on therapeutic effect of Infliximab on ulcerative colitis
S288
Abstracts
creatitis in this patient population is related either to medications. However, inflammation of the ampulla of Vater causing papillary incompetence with duodenal reflux into the pancreatic duct or a fistula between the duodenum and the pancreas can potentially result in the onset of pancreatitis. We report 2 children who presented with pancreatitis as the first manifestation of IBD, prior to the initiation of pharmacological therapy. Results: Case 1: 13 year old male presented with 10-day history of crampy, epigastric abdominal pain, which was worse after meals. He reported 2–3 loose stools, without visible blood. His physical exam revealed mild tenderness on deep palpation of the epigastric area, decreased bowel sounds and hemeoccult positive stool. Laboratory evaluation revealed a lipase of 703 IU/L, amylase of 202 IU/L, sedimentation rate of 106 mm/hr with a normal hemoglobin level. US and CT of abdomen were normal. After resolution of the pancreatitis the patient underwent endoscopic evaluation. EGD was visually and histologically normal. There was no evidence of duodenitis. Colonoscopy was consistent with active chronic IBD, favoring Crohn’s disease. Case 2: 14 year old male presented with a 3-month history of non-specific abdominal pain, 10-LB weight loss and decreased appetite. On exam, he was a sick appearing child, with significant epigastric tenderness, voluntary guarding, decreased bowel sounds and hemeoccult negative stool. Laboratory evaluation revealed an amylase of 536 IU/L and lipase of 551 IU/L, sedimentation rate of 36 mm/hr with a normal hemoglobin level. US and CT of abdomen were normal. On EGD, the duodenum was grossly and histologically there was a diffuse increase in inflammatory cells in the lamina propria. Colonoscopy was diagnostic of Crohn’s disease. Conclusions: Pancreatitis may be the initial presenting symptom of IBD in children. In these two children the pancreatitis appears to be unrelated to duodenal disease or medications, and may be “new” extraintestinal manifestation of IBD.
915 Observations on therapeutic effect of Infliximab on ulcerative colitis William Y Chey, MD, FACGRI*, George Y Kunze, MDUR and Ashok N Shah, MDUR. 1Gastroenterology, Rochester Institute for Digestive & Liver Diseases, Rochester, New York, United States; and 2Medicine, GI, University of Rochester Medical Center, Rochester, New York, United States. Purpose: The Purpose of this study is to further evaluate the efficacy of Infliximab. We have recently reported our preliminary observation that Infliximab, a TNF-␣ Antibody, given iv at a dose of 5 mg/kg is an effective therapeutic agent for ulcerative colitis in 8 patients who were refractory to 5-ASA and/or 6-mercaptopurine and were prednisone-dependent or refractory to prednisone, showing significant improvements in clinical, endoscopic and histological features (Am J Gastroent, Aug.’01). Methods: The study has been expanded in 31 consecutive patients including 4 with severe pouchitis, they include 17 males and 14 females with ages ranging from 18 to 77 yrs (mean: 48.5 ⫾ 3.4 yrs). Among 18 pts so tested, serum pANCA was positive in 17 and ASCA, positive in 1. The duration of clinical observations ranged between 6 and 30 months. Clinical and endoscopic responses to infliximab at 5 mg/kg were determined and also, the course of prednisone usage after infliximab therapy was monitored. A significant clinical improvement was considered when the improvement lasted at least 3 months or longer. Results: Of 31 pts, the infliximab administration resulted in an excellent clinical response in 27 pts including 4 pouchitis pts (87%). All 27 had become asymptomatic within one to two weeks and duration of clinical remission ranged from 3 months to 30 months with a mean (⫾SE)of 11.5 (⫾5.6)months, thus the mean ulcerative colitis clinical activity index decreased significantly from 17 ⫾ 15.81 ⫾ 0.5 (SE) to 3.3 ⫾ 0.9 (SE) (P ⬍ 0.001). Endoscopic improvement paralleled clinical improvement in all 27. Of 28 pts who were on prednisone at the time of infliximab infusion, 24 pts were weaned from prednisone. Of the 4 pts who failed to improve clinically and endoscopically, 1 pt dramatically improved after iv infusion of inflix-
AJG – Vol. 96, No. 9, Suppl., 2001
imab at 10 mg/kg and the remaining 3 had total colectomy. Only one patient experienced an anaphyctoid reaction during the infliximab infusion which was promptly relieved by iv Solu-Medrol. Conclusions: Infliximab is effective in treatment of ulcerative colitis pts, refractory to conventional therapeutic agents including 5-ASA, prednisone and 6-MP. Moreover, prednisone can be weaned in the majority of prednisone-dependent pts. Infliximab is a safe drug for ulcerative colitis (Supported in part by Konar Foundation). 916 Quality of life in Crohn’s disease: the big picture Russell D Cohen1*. 1Department of Medicine, University of Chicago, Chicago, IL, United States. Purpose: To compare health-related quality of life (HRQOL) and health care utility in Crohn’s disease (CD) to that in other disease states, and determine the impact of disease activity and medical or surgical intervention upon HRQOL. Methods: Medline search (1966 –9/2000) of English-language articles using key words “Quality of life”, “Health Status”, or “Health Related Quality of Life” and either “Crohn’s” or “Inflammatory Bowel Disease. Additional references from review articles and textbooks. Adult patients only. Study quality assessment (English language, full-length manuscript, CD data reported separately from IBD data, verification of CD, and validation of HRQOL questionniares) tabulated. Five study questions applied: #1) Crohn’s vs. healthy controls; #2)Crohn’s vs. other diseases; #3)active vs. inactive Crohn’s; #4) correlation with disease activity; #5)medical vs. surgical therapy. Disease-specific scales utilized: Inflammatory Bowel Disease Questionnaire (IBDQ) or variants (vIBDQ), Cleveland Clinic Scale, Rating From of IBD Patient Concern (RFIPC). General HRQOL scales utilized: Sickness Impact Profile (SIP), Psychological General Well-Being Index (PGWBI), EuroQOL, Symptom Checklist (SCL90), Global Symptom Index (GSI), Beck Depression Inventory (Beck), Short Form-36(SF), Health Status Questionniare (HSQ) Utility Scales utilized: Time-trade Off (TTO), Standard Gamble (SG), Direct Questioning of Objective (DQO). Generic scales utilized: Patient Global Rating (PGR), Visual Analog Scale (VAS). Results: 258 articles identified; 21 met inclusion criteria. Exclusions: no HRQOL analysis(171), not Crohn’s(27), pediatric(22), epidemiology/historical(13), duplicate(3), abstract(1). Results for each of 5 questions follows. #1)HRQOL is worse in CD than in healthy controls, except for physical functioning. (vIBDQ, SIP) #2)HRQOL is generally worse in CD than in ulcerative colitis, but similar to or better than other medical disorders studied. (SIP, RFIPC, Cleveland, vIBDQ, IBDQ, GSI, SCL-90) #3)HRQOL is worse in active CD than inactive. (vIBDQ, PGWBI, EuroQOL, IBDQ, SIP, SCL-90, GSI, TTO, SG, VAS, PGR) #4) HRQOL is directly correlated with disease activity. (SIP, IBDQ, vIBDQ, RFIPC, VAS, TTO, SG, PGR) #5) HRQOL is better in surgically treated patients in the immediate post-operative period, but not in the long-term. (vIBDQ, PGWBI, EuroQOL, HSQ, TTO, DQO, RFIPC, Beck, SF) Conclusions: HRQOL is reduced in many instances in CD patients. Inclusion of formal HRQOL and utility analyses in clinical trials and other studies of CD patients, and increasing the awareness of HRQOL issues among health care providers is strongly encouraged. (Research funded by Astra-Zeneca)
917 Pharmacogenomics of azathioprine (AZA) metabolism in IBD: Correlation with treatment efficacy C. Cuffari, TM. Bayless*. Depts. of Pediatrics, and Medicine, *The Johns Hopkins University, Baltimore, USA. Genetic polymorphism of thiopurine methyl transferase (TPMT), the key enzyme involved in AZA catabolism, are well known to influence clinical
Abstracts
creatitis in this patient population is related either to medications. However, inflammation of the ampulla of Vater causing papillary incompetence with duodenal reflux into the pancreatic duct or a fistula between the duodenum and the pancreas can potentially result in the onset of pancreatitis. We report 2 children who presented with pancreatitis as the first manifestation of IBD, prior to the initiation of pharmacological therapy. Results: Case 1: 13 year old male presented with 10-day history of crampy, epigastric abdominal pain, which was worse after meals. He reported 2–3 loose stools, without visible blood. His physical exam revealed mild tenderness on deep palpation of the epigastric area, decreased bowel sounds and hemeoccult positive stool. Laboratory evaluation revealed a lipase of 703 IU/L, amylase of 202 IU/L, sedimentation rate of 106 mm/hr with a normal hemoglobin level. US and CT of abdomen were normal. After resolution of the pancreatitis the patient underwent endoscopic evaluation. EGD was visually and histologically normal. There was no evidence of duodenitis. Colonoscopy was consistent with active chronic IBD, favoring Crohn’s disease. Case 2: 14 year old male presented with a 3-month history of non-specific abdominal pain, 10-LB weight loss and decreased appetite. On exam, he was a sick appearing child, with significant epigastric tenderness, voluntary guarding, decreased bowel sounds and hemeoccult negative stool. Laboratory evaluation revealed an amylase of 536 IU/L and lipase of 551 IU/L, sedimentation rate of 36 mm/hr with a normal hemoglobin level. US and CT of abdomen were normal. On EGD, the duodenum was grossly and histologically there was a diffuse increase in inflammatory cells in the lamina propria. Colonoscopy was diagnostic of Crohn’s disease. Conclusions: Pancreatitis may be the initial presenting symptom of IBD in children. In these two children the pancreatitis appears to be unrelated to duodenal disease or medications, and may be “new” extraintestinal manifestation of IBD.
915 Observations on therapeutic effect of Infliximab on ulcerative colitis William Y Chey, MD, FACGRI*, George Y Kunze, MDUR and Ashok N Shah, MDUR. 1Gastroenterology, Rochester Institute for Digestive & Liver Diseases, Rochester, New York, United States; and 2Medicine, GI, University of Rochester Medical Center, Rochester, New York, United States. Purpose: The Purpose of this study is to further evaluate the efficacy of Infliximab. We have recently reported our preliminary observation that Infliximab, a TNF-␣ Antibody, given iv at a dose of 5 mg/kg is an effective therapeutic agent for ulcerative colitis in 8 patients who were refractory to 5-ASA and/or 6-mercaptopurine and were prednisone-dependent or refractory to prednisone, showing significant improvements in clinical, endoscopic and histological features (Am J Gastroent, Aug.’01). Methods: The study has been expanded in 31 consecutive patients including 4 with severe pouchitis, they include 17 males and 14 females with ages ranging from 18 to 77 yrs (mean: 48.5 ⫾ 3.4 yrs). Among 18 pts so tested, serum pANCA was positive in 17 and ASCA, positive in 1. The duration of clinical observations ranged between 6 and 30 months. Clinical and endoscopic responses to infliximab at 5 mg/kg were determined and also, the course of prednisone usage after infliximab therapy was monitored. A significant clinical improvement was considered when the improvement lasted at least 3 months or longer. Results: Of 31 pts, the infliximab administration resulted in an excellent clinical response in 27 pts including 4 pouchitis pts (87%). All 27 had become asymptomatic within one to two weeks and duration of clinical remission ranged from 3 months to 30 months with a mean (⫾SE)of 11.5 (⫾5.6)months, thus the mean ulcerative colitis clinical activity index decreased significantly from 17 ⫾ 15.81 ⫾ 0.5 (SE) to 3.3 ⫾ 0.9 (SE) (P ⬍ 0.001). Endoscopic improvement paralleled clinical improvement in all 27. Of 28 pts who were on prednisone at the time of infliximab infusion, 24 pts were weaned from prednisone. Of the 4 pts who failed to improve clinically and endoscopically, 1 pt dramatically improved after iv infusion of inflix-
AJG – Vol. 96, No. 9, Suppl., 2001
imab at 10 mg/kg and the remaining 3 had total colectomy. Only one patient experienced an anaphyctoid reaction during the infliximab infusion which was promptly relieved by iv Solu-Medrol. Conclusions: Infliximab is effective in treatment of ulcerative colitis pts, refractory to conventional therapeutic agents including 5-ASA, prednisone and 6-MP. Moreover, prednisone can be weaned in the majority of prednisone-dependent pts. Infliximab is a safe drug for ulcerative colitis (Supported in part by Konar Foundation). 916 Quality of life in Crohn’s disease: the big picture Russell D Cohen1*. 1Department of Medicine, University of Chicago, Chicago, IL, United States. Purpose: To compare health-related quality of life (HRQOL) and health care utility in Crohn’s disease (CD) to that in other disease states, and determine the impact of disease activity and medical or surgical intervention upon HRQOL. Methods: Medline search (1966 –9/2000) of English-language articles using key words “Quality of life”, “Health Status”, or “Health Related Quality of Life” and either “Crohn’s” or “Inflammatory Bowel Disease. Additional references from review articles and textbooks. Adult patients only. Study quality assessment (English language, full-length manuscript, CD data reported separately from IBD data, verification of CD, and validation of HRQOL questionniares) tabulated. Five study questions applied: #1) Crohn’s vs. healthy controls; #2)Crohn’s vs. other diseases; #3)active vs. inactive Crohn’s; #4) correlation with disease activity; #5)medical vs. surgical therapy. Disease-specific scales utilized: Inflammatory Bowel Disease Questionnaire (IBDQ) or variants (vIBDQ), Cleveland Clinic Scale, Rating From of IBD Patient Concern (RFIPC). General HRQOL scales utilized: Sickness Impact Profile (SIP), Psychological General Well-Being Index (PGWBI), EuroQOL, Symptom Checklist (SCL90), Global Symptom Index (GSI), Beck Depression Inventory (Beck), Short Form-36(SF), Health Status Questionniare (HSQ) Utility Scales utilized: Time-trade Off (TTO), Standard Gamble (SG), Direct Questioning of Objective (DQO). Generic scales utilized: Patient Global Rating (PGR), Visual Analog Scale (VAS). Results: 258 articles identified; 21 met inclusion criteria. Exclusions: no HRQOL analysis(171), not Crohn’s(27), pediatric(22), epidemiology/historical(13), duplicate(3), abstract(1). Results for each of 5 questions follows. #1)HRQOL is worse in CD than in healthy controls, except for physical functioning. (vIBDQ, SIP) #2)HRQOL is generally worse in CD than in ulcerative colitis, but similar to or better than other medical disorders studied. (SIP, RFIPC, Cleveland, vIBDQ, IBDQ, GSI, SCL-90) #3)HRQOL is worse in active CD than inactive. (vIBDQ, PGWBI, EuroQOL, IBDQ, SIP, SCL-90, GSI, TTO, SG, VAS, PGR) #4) HRQOL is directly correlated with disease activity. (SIP, IBDQ, vIBDQ, RFIPC, VAS, TTO, SG, PGR) #5) HRQOL is better in surgically treated patients in the immediate post-operative period, but not in the long-term. (vIBDQ, PGWBI, EuroQOL, HSQ, TTO, DQO, RFIPC, Beck, SF) Conclusions: HRQOL is reduced in many instances in CD patients. Inclusion of formal HRQOL and utility analyses in clinical trials and other studies of CD patients, and increasing the awareness of HRQOL issues among health care providers is strongly encouraged. (Research funded by Astra-Zeneca)
917 Pharmacogenomics of azathioprine (AZA) metabolism in IBD: Correlation with treatment efficacy C. Cuffari, TM. Bayless*. Depts. of Pediatrics, and Medicine, *The Johns Hopkins University, Baltimore, USA. Genetic polymorphism of thiopurine methyl transferase (TPMT), the key enzyme involved in AZA catabolism, are well known to influence clinical