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Herpetic esophagitis secondary to infliximab infusion
S310
Abstracts
982 Efficacy of anti-tumor necrosis factor therapy in patients with ulcerative colitis Chinyu G Su1, Bruce Salzberg2, James Lewis1, Julius Deren1, Asher Kornbluth3, David Katzka1, Robert Stein1, Douglas Adler4 and Gary R Lichtenstein1*. 1Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States; 2Atlanta Gastroenterology Associates, Atlanta, Georgia, United States; 3 Medicine, Mount Sinai School of Medicine, New York, New York, United States; and 4Lutheran General Hospital, Park Ridge, Illinois, United States. Purpose: Tumor Necrosis Factor-alpha (TNF-␣) is an important cytokine in inflammatory bowel disease. Antibody to TNF-␣, infliximab is effective therapy for Crohn’s disease. Two pilot studies have suggested efficacy of one or two infliximab infusions in patients with severe UC. The role of infliximab in repeat infusions and analysis of variables that predict patient nonresponse to infliximab have not been critically analyzed. This study reports the efficacy of infliximab in these patient populations. Methods: UC patients who received infliximab at 4 centers were analyzed. Outcomes defined by clinical response included remission-return to baseline stool frequency and absence of rectal bleeding; partial responsesubstantial but incomplete clinical improvement based on stool frequency and rectal bleeding; and no response. Results: 28 patients received inpatient (36%) and outpatient (64%) infliximab at single (50% of all patients) or multiple (2–15) infusions (50% of all patients). One patient received 5 mg/kg of infliximab as maintenance therapy after 3 infusions at 3 mg/kg for recurrence. Other patients received infliximab at 5 mg/kg, including one patient receiving three infusions at 5 mg/kg at week 0, 2, and 6 from the onset. 24 patients (86%) had severe UC, 2 patients had moderately active UC, one had mildly active UC, and one had refractory chronic pouchitis with cuffitis following total proctocolectomy with ileoanal J pouch for pancolitis. 10 patients (36%) were steroiddependent, and 9 (32%) were steroid-refractory. Most patients had been treated with (57%) or refused (25%) immunomodulatory therapy. 19 patients responded (67%) and 13 of these patients (46%) achieved clinical remission. 9 patients had no response, 5 of them subsequently underwent total colectomy. The remission rate at 6 months following the initial infusion was 55%. Steroid-reduction was demonstrated in 90% of steroiddependent patients. Patients with steroid refractory disease were less likely to respond than those without steroid-refractory disease (33% vs. 84%, p ⫽ 0.013). The response was rapid; the median time to achieve clinical response was 4 days, and the median time to relapse was 8 weeks. 95% of relapses responded to repeat infusions. Conclusions: Anti-TNF-␣ directed therapy, infliximab, may be effective in the treatment of patients with UC. Those patients with steroid refractory disease appear to be less likely to respond. Additionally, our preliminary data suggests efficacy of infliximab as a steroid sparing and maintenance agent. A large, randomized controlled trial is necessary to further investigate its efficacy.
983 Incidence of Helicobacter pylori infection in pediatric inflammatory bowel disease patients Husam H Sukerek, MD1, Ronald L Thomas, PhD1 and Vasundhara K Tolia, MD1*. 1Division of Gastroenterology, Children’s Hospital of Michigan, Detroit, Michigan, United States. Purpose: Gastritis as part of Upper gastrointestinal tract involvement, is a common finding in patients with inflammatory bowel disease (IBD), however, concurrent Helicobacter pylori (H. pylori) infection has been reported infrequently. We performed a study to compare the incidence of H. pylori infection in pediatric IBD and in an age and sex matched control group without IBD, requiring an upper endoscopy. Methods: Charts of 38 patients with IBD and 38 age and sex matched controls were reviewed. Amongst patients with IBD, 20 had Crohn’s
AJG – Vol. 96, No. 9, Suppl., 2001
disease (CD), 13 ulcerative colitis (UC), and 5 indeterminate colitis. Their mean disease duration was 4.7 years; range 1–14 years, and most were on maintenance treatment with mesalamine and azathioprine. A few were on prednisone. H. pylori IgG titers were measured by a validated enzyme immunoassay for pediatric age group in both groups. An esophagogastroduodenoscopy (EGD) was performed on all patients for routine clinical indications and biopsies were obtained from distal esophagus, gastric corpus, gastric antrum, and duodenum. A CLO test was performed in all antral biopsies.
Mean age (years) Male/female % of patients Positive for H. pylori on serology % of patients Positive for H. pylori on histology/CLO test Other abnormalities (esophagitis, H. pylori negative gastritis, duodenitis)
IBD patients
Controls
P Value
15.3 18/20 7.9
12.7 18/20 13.2
0.647
5.3/5.3
13.2/13.2
0.364
84.3
73.3
Conclusions: Our findings suggest lower incidence of H. pylori infection in Pediatric IBD patients in comparison with controls (5.3% vs. 13.2%, P ⫽ 0.364). Although, these findings were not statistically significant, it is interesting to find that despite being on chronic immunosuppression, H. pylori infection in IBD patients was low.
984 Herpetic esophagitis secondary to infliximab infusion Shams Tabrez, M.D., Ofelia Balta, M.D., Houssam Alkharrat, M.D., Alan Nelson, M.D., David Grayer, M.D.* and Ingram Roberts, M.D. Gastroenterology, Yale-New Haven Health, Bridgeport Hospital., Bridgeport, CT. Purpose: Infliximab is one of the Tumor necrosis factor-alpha (TNF-alpha) antibody which has been used since August 1998 when US Food and Drug Administration approved it for patients with active enteric and fistulizing Crohn’s disease. Side effects of therapy include upper respiratory tract infection, abdominal pain, myalgias, nausea, fatigue, lupus-like reactions, and lymphomas. As infliximab has been used with increasing frequency, new side effects are now being described. Methods: We had encountered an 82-year-old female, with known Crohn’s Disease for 40 years; status post left hemicolectomy with colostomy several years ago. She was admitted with severe colicky abdominal pain, bloody diarrhea, and weakness. CT scan of the abdomen and colonoscopy through the stoma demonstrated severe Crohn’s disease with crypt-abcesses and multiple deep ulcerations extending through the muscularis mucosae. The work-up of infectious etiology was negative. She was treated with intravenous steroids and antibiotics for 48 hours, but continued to have profuse bleeding, necessitating transfusion of several units of blood. She was given a course of infliximab (5 mg/kg over 2 hours) with great improvement in her bleeding, diarrhea and pain. Few days later she noted dysphagia and odynophagia. She underwent upper endoscopy, which showed multiple large esophageal ulcers, biopsy revealed “extensive Herpetic inclusion bodies”. The patient was started on Famciclovir 250 mg PO TID, and over the next seven days she had a dramatic improvement. She was able to be discharged home on Famciclovir, Carafate, Asacol, and hydrocortisone enema. Conclusions: Although efficacy of infliximab in moderately severe active Crohn’s Disease has already been proven in large studies, side effects remain to be explored. This is an unusual adverse effect of infliximab. There is data to suggest that TNF-alpha antagonism may specifically augment apoptosis of proliferating T-cells. It could be hypothesized that the reduction in the T-lymphocytes described as infliximab effect might predispose to viral infections. Additional long-term data being necessary to determine side effects, we thought that such reports are necessary to complete the picture of this wonderful drug.
Abstracts
982 Efficacy of anti-tumor necrosis factor therapy in patients with ulcerative colitis Chinyu G Su1, Bruce Salzberg2, James Lewis1, Julius Deren1, Asher Kornbluth3, David Katzka1, Robert Stein1, Douglas Adler4 and Gary R Lichtenstein1*. 1Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States; 2Atlanta Gastroenterology Associates, Atlanta, Georgia, United States; 3 Medicine, Mount Sinai School of Medicine, New York, New York, United States; and 4Lutheran General Hospital, Park Ridge, Illinois, United States. Purpose: Tumor Necrosis Factor-alpha (TNF-␣) is an important cytokine in inflammatory bowel disease. Antibody to TNF-␣, infliximab is effective therapy for Crohn’s disease. Two pilot studies have suggested efficacy of one or two infliximab infusions in patients with severe UC. The role of infliximab in repeat infusions and analysis of variables that predict patient nonresponse to infliximab have not been critically analyzed. This study reports the efficacy of infliximab in these patient populations. Methods: UC patients who received infliximab at 4 centers were analyzed. Outcomes defined by clinical response included remission-return to baseline stool frequency and absence of rectal bleeding; partial responsesubstantial but incomplete clinical improvement based on stool frequency and rectal bleeding; and no response. Results: 28 patients received inpatient (36%) and outpatient (64%) infliximab at single (50% of all patients) or multiple (2–15) infusions (50% of all patients). One patient received 5 mg/kg of infliximab as maintenance therapy after 3 infusions at 3 mg/kg for recurrence. Other patients received infliximab at 5 mg/kg, including one patient receiving three infusions at 5 mg/kg at week 0, 2, and 6 from the onset. 24 patients (86%) had severe UC, 2 patients had moderately active UC, one had mildly active UC, and one had refractory chronic pouchitis with cuffitis following total proctocolectomy with ileoanal J pouch for pancolitis. 10 patients (36%) were steroiddependent, and 9 (32%) were steroid-refractory. Most patients had been treated with (57%) or refused (25%) immunomodulatory therapy. 19 patients responded (67%) and 13 of these patients (46%) achieved clinical remission. 9 patients had no response, 5 of them subsequently underwent total colectomy. The remission rate at 6 months following the initial infusion was 55%. Steroid-reduction was demonstrated in 90% of steroiddependent patients. Patients with steroid refractory disease were less likely to respond than those without steroid-refractory disease (33% vs. 84%, p ⫽ 0.013). The response was rapid; the median time to achieve clinical response was 4 days, and the median time to relapse was 8 weeks. 95% of relapses responded to repeat infusions. Conclusions: Anti-TNF-␣ directed therapy, infliximab, may be effective in the treatment of patients with UC. Those patients with steroid refractory disease appear to be less likely to respond. Additionally, our preliminary data suggests efficacy of infliximab as a steroid sparing and maintenance agent. A large, randomized controlled trial is necessary to further investigate its efficacy.
983 Incidence of Helicobacter pylori infection in pediatric inflammatory bowel disease patients Husam H Sukerek, MD1, Ronald L Thomas, PhD1 and Vasundhara K Tolia, MD1*. 1Division of Gastroenterology, Children’s Hospital of Michigan, Detroit, Michigan, United States. Purpose: Gastritis as part of Upper gastrointestinal tract involvement, is a common finding in patients with inflammatory bowel disease (IBD), however, concurrent Helicobacter pylori (H. pylori) infection has been reported infrequently. We performed a study to compare the incidence of H. pylori infection in pediatric IBD and in an age and sex matched control group without IBD, requiring an upper endoscopy. Methods: Charts of 38 patients with IBD and 38 age and sex matched controls were reviewed. Amongst patients with IBD, 20 had Crohn’s
AJG – Vol. 96, No. 9, Suppl., 2001
disease (CD), 13 ulcerative colitis (UC), and 5 indeterminate colitis. Their mean disease duration was 4.7 years; range 1–14 years, and most were on maintenance treatment with mesalamine and azathioprine. A few were on prednisone. H. pylori IgG titers were measured by a validated enzyme immunoassay for pediatric age group in both groups. An esophagogastroduodenoscopy (EGD) was performed on all patients for routine clinical indications and biopsies were obtained from distal esophagus, gastric corpus, gastric antrum, and duodenum. A CLO test was performed in all antral biopsies.
Mean age (years) Male/female % of patients Positive for H. pylori on serology % of patients Positive for H. pylori on histology/CLO test Other abnormalities (esophagitis, H. pylori negative gastritis, duodenitis)
IBD patients
Controls
P Value
15.3 18/20 7.9
12.7 18/20 13.2
0.647
5.3/5.3
13.2/13.2
0.364
84.3
73.3
Conclusions: Our findings suggest lower incidence of H. pylori infection in Pediatric IBD patients in comparison with controls (5.3% vs. 13.2%, P ⫽ 0.364). Although, these findings were not statistically significant, it is interesting to find that despite being on chronic immunosuppression, H. pylori infection in IBD patients was low.
984 Herpetic esophagitis secondary to infliximab infusion Shams Tabrez, M.D., Ofelia Balta, M.D., Houssam Alkharrat, M.D., Alan Nelson, M.D., David Grayer, M.D.* and Ingram Roberts, M.D. Gastroenterology, Yale-New Haven Health, Bridgeport Hospital., Bridgeport, CT. Purpose: Infliximab is one of the Tumor necrosis factor-alpha (TNF-alpha) antibody which has been used since August 1998 when US Food and Drug Administration approved it for patients with active enteric and fistulizing Crohn’s disease. Side effects of therapy include upper respiratory tract infection, abdominal pain, myalgias, nausea, fatigue, lupus-like reactions, and lymphomas. As infliximab has been used with increasing frequency, new side effects are now being described. Methods: We had encountered an 82-year-old female, with known Crohn’s Disease for 40 years; status post left hemicolectomy with colostomy several years ago. She was admitted with severe colicky abdominal pain, bloody diarrhea, and weakness. CT scan of the abdomen and colonoscopy through the stoma demonstrated severe Crohn’s disease with crypt-abcesses and multiple deep ulcerations extending through the muscularis mucosae. The work-up of infectious etiology was negative. She was treated with intravenous steroids and antibiotics for 48 hours, but continued to have profuse bleeding, necessitating transfusion of several units of blood. She was given a course of infliximab (5 mg/kg over 2 hours) with great improvement in her bleeding, diarrhea and pain. Few days later she noted dysphagia and odynophagia. She underwent upper endoscopy, which showed multiple large esophageal ulcers, biopsy revealed “extensive Herpetic inclusion bodies”. The patient was started on Famciclovir 250 mg PO TID, and over the next seven days she had a dramatic improvement. She was able to be discharged home on Famciclovir, Carafate, Asacol, and hydrocortisone enema. Conclusions: Although efficacy of infliximab in moderately severe active Crohn’s Disease has already been proven in large studies, side effects remain to be explored. This is an unusual adverse effect of infliximab. There is data to suggest that TNF-alpha antagonism may specifically augment apoptosis of proliferating T-cells. It could be hypothesized that the reduction in the T-lymphocytes described as infliximab effect might predispose to viral infections. Additional long-term data being necessary to determine side effects, we thought that such reports are necessary to complete the picture of this wonderful drug.