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Efficacy and tolerability of rifaximin, a nonabsorbed oral antibiotic, in the treatment of active Crohn’s disease: results of an open-label study
S250
Abstracts
of circulating lymphocytes, an effect that is believed to contribute to the increased risk of infection in patients receiving such treatment. Medroxyprogesterone acetate (MPA), a progestational agent and partial glucocorticoid agonist/antagonist, differs strikingly from glucocorticoids in the degree to which it activates genes associated with glucocorticoid side effects. MPA has been evaluated with encouraging results in an animal model for IBD and in three open-label clinical trials in three disorders responsive to glucocorticoid therapy: Crohn’s disease, ulcerative colitis and the autoimmune disorder, idiopathic thrombocytopenic purpura (ITP). Methods: We determined serial lymphocyte and granulocyte counts prospectively in patients during 6-8 week clinical trials in IBD and ITP. Results: In contrast to glucocorticoids, MPA did not cause a decrease in the absolute lymphocyte count. Rather, MPA induced an increase in the lymphocyte count in each trial. The increase in lymphocyte count was observed after one week of treatment and was sustained over 6-8 weeks of therapy. MPA did not induce a consistent increase in the percentage of neutrophils, also differing in this respect from glucocorticoids, which typically induce an increase in neutrophil count. Conclusions: A possible explanation for the differential effects of MPA and classic glucocorticoids is that MPA-bound glucocorticoid receptors may have conformational changes that differentially affect interactions with genes related to glucocorticoid side effects, but not genes related to glucocorticoid anti-inflammatory effects. In summary, data derived from 3 clinical trials indicate that the use of MPA as an anti-inflammatory agent to treat glucocorticoid responsive disorders protects against the glucocorticoid lymphopenic effect.
753 THE EFFECT OF A 24-WEEK EXERCISE PROGRAM ON BONE MINERAL DENSITY AMONG PATIENTS WITH CROHN’S DISEASE: A RANDOMIZED CONTROL TRIAL Terry P. Ponich, M.D.*, Sinead P. O’Sullivan, M.Sc., Keith Sparrow, M.D., Pauline Walton-Mennill, R.N. University of Western Ontario, London, ON, Canada. Purpose: A growing body of evidence suggests that individuals with inflammatory bowel disease (IBD), especially Crohn’s disease (CD) are at an increased risk for developing reduced bone mineral density (BMD). Weight bearing exercise is regularly prescribed as a treament and prevention strategy for post-menopausal osteoporosis. However, there is very little literature investigating the effects of exercise on secondary osteoporosis. The purpose of this study was to determine the effects of a 24-week supervised resistance training program on patients with CD. Methods: Patients with a diagnosis of CD who attended the IBD out patient clinic at London Health Sciences Center, Victoria Campus, were invited to participate in the study. Patients were recruited consecutively until 24 patients were enrolled. Patients were then assigned to either the exercise group or control group by means of a random draw. All participants in the study received the same standardized supplementry calcium and vitamin D throught the duration of the study. Participants randomized to the exercise group underwent 24 weeks of progressive resistance training, three times a week. The primary outcome measure of this study is BMD test scores. Secondary outcomes include the SF-36 self perceived health questionnaire, grip strength and 2-Minute Walk Test (2MW). Measures were taken at baseline, 12 and 24 weeks. Results: Independant samples t-tests were condcuted to determine significance bewteen the exercise group and control group from baseline to 12 weeks (pⱕ0.05). All variables improved to a greater degree for the exercise group compared to the control group. SF-36 increased significantly in the first 12-weeks in the exercise group (p⫽0.042), likewise grip strength (p⫽0.038) and 2MW scores (p⫽0.003) improved significally compared to the control group. While BMD overall did not improve significanly in either group, there was a tread toward significance for hip BMD for the exercise group (p⫽0.075). Final analysis is currenly underway. Conclusions: A structured exercise program has a multitude of befefits for patients with CD. Fitness level and perceived overall health are signifi-
AJG – Vol. 98, No. 9, Suppl., 2003
cantly enhanced with structured exercise among this population. Additionally, resistance exercise has a positive yet not significant effect of BMD. This study provides evidence to support exercise prescription as an adjuct therapy for patients with CD.
754 EFFICACY AND TOLERABILITY OF RIFAXIMIN, A NONABSORBED ORAL ANTIBIOTIC, IN THE TREATMENT OF ACTIVE CROHN’S DISEASE: RESULTS OF AN OPENLABEL STUDY Ira Shafran, M.D.*, Lorin K. Johnson, Ph.D., Lynne Hamm, Robert H. Murdock, Jr. Shafran Gastroenterology Center, Winter Park, FL and Salix Pharmaceuticals, Inc., Raleigh, NC. Purpose: Rifaximin is a nonabsorbed (⬍0.5%), gut-selective oral antibiotic with broad-spectrum activity against gram-positive and gram-negative enteric organisms. This open-label study was conducted to evaluate the efficacy and safety of rifaximin for active Crohn’s disease. Methods: The efficacy and safety of rifaximin (200 mg tid for 16 weeks) for Crohn’s disease (confirmed by endoscopy, surgical pathology, or X-ray) were assessed in patients with symptoms of active Crohn’s disease for at least 3 months before screening and a Crohn’s Disease Activity Index (CDAI) score ⬎220 and ⬍400. Preliminary analyses were performed on data from 21 patients. Results: The results show that, at the end of treatment week 16, rifaximin reduced mean CDAI score by 43% compared with baseline (baseline mean⫽280; week 16 mean⫽161; primary endpoint). More than half of patients (57%) exhibited a ⬎70-point improvement in CDAI score beginning with the first assessment at the end treatment week 4. By the end of the treatment period, 81% of patients showed a ⬎70-point improvement in CDAI score. Clinical remission, defined as CDAI score ⬍150, was achieved at the end of treatment weeks 4, 8, 12, and 16 by 33%, 52%, 52%, and 62% of patients, respectively. The corresponding proportions of patients with improvement in daily diary ratings of clinical status were 81%, 90%, 86%, and 86%, respectively. Rifaximin was well-tolerated. Conclusions: These data, which suggest that rifaximin may be effective and well-tolerated in the treatment of active Crohn’s disease, warrant confirmation in a randomized, double-blind, placebo-controlled trial.
755 TREATMENT OF CUTANEOUS CROHN’S DISEASE WITH INFLIXIMAB Sara H. Mitchell, M.D., Vincent J. Varano, M.D.*, Michael J. Komar, M.D. Geisinger Medical Center, Danville, PA. Purpose: Cutaneous or metastatic Crohn’s disease is extremely rare. Treatment to this date has been sub optimal, but normally consists of steroids, immunosuppression, and occasionally intralesional injection of steroids. We present a case of cutaneous Crohn’s disease that was successfully treated with Infliximab. Methods: A 60 year-old white male with history hypertension, asthma, hypertrophic obstructive cardiomyopathy, and Crohn’s disease since 1985 presented with a flare of his Crohn’s disease in April 2001. He was treated with oral mesalamine and steroids, but developed painful skin lesions one month later. On examination he had multiple inflammatory nodules on his arms and legs with erythema and central ulceration. There was some central hemorrhage and peripheral scaling. Biopsies showed granulomatous dermatitis with mixed inflammatory infiltrate, reactive epidermal hyperplasia, and dermal fibrosis, consistent with cutaneous Crohn’s disease. No features of pyoderma gangrenosum were noted, or evidence for acid-fast bacilli, fungi or bacteria seen on specialized stains. The patient was treated with oral steroids and metronidazole. He had mild improvement, and was then treated with intralesional steroids. Ultimately, he was started on IV Infliximab for continued flares of Crohn’s symptoms. This helped both bowel and skin symptoms, and he was started on maintenance Infliximab therapy.
Abstracts
of circulating lymphocytes, an effect that is believed to contribute to the increased risk of infection in patients receiving such treatment. Medroxyprogesterone acetate (MPA), a progestational agent and partial glucocorticoid agonist/antagonist, differs strikingly from glucocorticoids in the degree to which it activates genes associated with glucocorticoid side effects. MPA has been evaluated with encouraging results in an animal model for IBD and in three open-label clinical trials in three disorders responsive to glucocorticoid therapy: Crohn’s disease, ulcerative colitis and the autoimmune disorder, idiopathic thrombocytopenic purpura (ITP). Methods: We determined serial lymphocyte and granulocyte counts prospectively in patients during 6-8 week clinical trials in IBD and ITP. Results: In contrast to glucocorticoids, MPA did not cause a decrease in the absolute lymphocyte count. Rather, MPA induced an increase in the lymphocyte count in each trial. The increase in lymphocyte count was observed after one week of treatment and was sustained over 6-8 weeks of therapy. MPA did not induce a consistent increase in the percentage of neutrophils, also differing in this respect from glucocorticoids, which typically induce an increase in neutrophil count. Conclusions: A possible explanation for the differential effects of MPA and classic glucocorticoids is that MPA-bound glucocorticoid receptors may have conformational changes that differentially affect interactions with genes related to glucocorticoid side effects, but not genes related to glucocorticoid anti-inflammatory effects. In summary, data derived from 3 clinical trials indicate that the use of MPA as an anti-inflammatory agent to treat glucocorticoid responsive disorders protects against the glucocorticoid lymphopenic effect.
753 THE EFFECT OF A 24-WEEK EXERCISE PROGRAM ON BONE MINERAL DENSITY AMONG PATIENTS WITH CROHN’S DISEASE: A RANDOMIZED CONTROL TRIAL Terry P. Ponich, M.D.*, Sinead P. O’Sullivan, M.Sc., Keith Sparrow, M.D., Pauline Walton-Mennill, R.N. University of Western Ontario, London, ON, Canada. Purpose: A growing body of evidence suggests that individuals with inflammatory bowel disease (IBD), especially Crohn’s disease (CD) are at an increased risk for developing reduced bone mineral density (BMD). Weight bearing exercise is regularly prescribed as a treament and prevention strategy for post-menopausal osteoporosis. However, there is very little literature investigating the effects of exercise on secondary osteoporosis. The purpose of this study was to determine the effects of a 24-week supervised resistance training program on patients with CD. Methods: Patients with a diagnosis of CD who attended the IBD out patient clinic at London Health Sciences Center, Victoria Campus, were invited to participate in the study. Patients were recruited consecutively until 24 patients were enrolled. Patients were then assigned to either the exercise group or control group by means of a random draw. All participants in the study received the same standardized supplementry calcium and vitamin D throught the duration of the study. Participants randomized to the exercise group underwent 24 weeks of progressive resistance training, three times a week. The primary outcome measure of this study is BMD test scores. Secondary outcomes include the SF-36 self perceived health questionnaire, grip strength and 2-Minute Walk Test (2MW). Measures were taken at baseline, 12 and 24 weeks. Results: Independant samples t-tests were condcuted to determine significance bewteen the exercise group and control group from baseline to 12 weeks (pⱕ0.05). All variables improved to a greater degree for the exercise group compared to the control group. SF-36 increased significantly in the first 12-weeks in the exercise group (p⫽0.042), likewise grip strength (p⫽0.038) and 2MW scores (p⫽0.003) improved significally compared to the control group. While BMD overall did not improve significanly in either group, there was a tread toward significance for hip BMD for the exercise group (p⫽0.075). Final analysis is currenly underway. Conclusions: A structured exercise program has a multitude of befefits for patients with CD. Fitness level and perceived overall health are signifi-
AJG – Vol. 98, No. 9, Suppl., 2003
cantly enhanced with structured exercise among this population. Additionally, resistance exercise has a positive yet not significant effect of BMD. This study provides evidence to support exercise prescription as an adjuct therapy for patients with CD.
754 EFFICACY AND TOLERABILITY OF RIFAXIMIN, A NONABSORBED ORAL ANTIBIOTIC, IN THE TREATMENT OF ACTIVE CROHN’S DISEASE: RESULTS OF AN OPENLABEL STUDY Ira Shafran, M.D.*, Lorin K. Johnson, Ph.D., Lynne Hamm, Robert H. Murdock, Jr. Shafran Gastroenterology Center, Winter Park, FL and Salix Pharmaceuticals, Inc., Raleigh, NC. Purpose: Rifaximin is a nonabsorbed (⬍0.5%), gut-selective oral antibiotic with broad-spectrum activity against gram-positive and gram-negative enteric organisms. This open-label study was conducted to evaluate the efficacy and safety of rifaximin for active Crohn’s disease. Methods: The efficacy and safety of rifaximin (200 mg tid for 16 weeks) for Crohn’s disease (confirmed by endoscopy, surgical pathology, or X-ray) were assessed in patients with symptoms of active Crohn’s disease for at least 3 months before screening and a Crohn’s Disease Activity Index (CDAI) score ⬎220 and ⬍400. Preliminary analyses were performed on data from 21 patients. Results: The results show that, at the end of treatment week 16, rifaximin reduced mean CDAI score by 43% compared with baseline (baseline mean⫽280; week 16 mean⫽161; primary endpoint). More than half of patients (57%) exhibited a ⬎70-point improvement in CDAI score beginning with the first assessment at the end treatment week 4. By the end of the treatment period, 81% of patients showed a ⬎70-point improvement in CDAI score. Clinical remission, defined as CDAI score ⬍150, was achieved at the end of treatment weeks 4, 8, 12, and 16 by 33%, 52%, 52%, and 62% of patients, respectively. The corresponding proportions of patients with improvement in daily diary ratings of clinical status were 81%, 90%, 86%, and 86%, respectively. Rifaximin was well-tolerated. Conclusions: These data, which suggest that rifaximin may be effective and well-tolerated in the treatment of active Crohn’s disease, warrant confirmation in a randomized, double-blind, placebo-controlled trial.
755 TREATMENT OF CUTANEOUS CROHN’S DISEASE WITH INFLIXIMAB Sara H. Mitchell, M.D., Vincent J. Varano, M.D.*, Michael J. Komar, M.D. Geisinger Medical Center, Danville, PA. Purpose: Cutaneous or metastatic Crohn’s disease is extremely rare. Treatment to this date has been sub optimal, but normally consists of steroids, immunosuppression, and occasionally intralesional injection of steroids. We present a case of cutaneous Crohn’s disease that was successfully treated with Infliximab. Methods: A 60 year-old white male with history hypertension, asthma, hypertrophic obstructive cardiomyopathy, and Crohn’s disease since 1985 presented with a flare of his Crohn’s disease in April 2001. He was treated with oral mesalamine and steroids, but developed painful skin lesions one month later. On examination he had multiple inflammatory nodules on his arms and legs with erythema and central ulceration. There was some central hemorrhage and peripheral scaling. Biopsies showed granulomatous dermatitis with mixed inflammatory infiltrate, reactive epidermal hyperplasia, and dermal fibrosis, consistent with cutaneous Crohn’s disease. No features of pyoderma gangrenosum were noted, or evidence for acid-fast bacilli, fungi or bacteria seen on specialized stains. The patient was treated with oral steroids and metronidazole. He had mild improvement, and was then treated with intralesional steroids. Ultimately, he was started on IV Infliximab for continued flares of Crohn’s symptoms. This helped both bowel and skin symptoms, and he was started on maintenance Infliximab therapy.