- Email: [email protected]
Low-dose heparin in active ulcerative colitis refractory to steroid therapy
2 7 -+ 2,7g/dl) There" was a positive correlation between s#rum hemoglobin and erythropoietin before treatment (r=0,720p<0,O01) and alier treatment (r=O,314,p=O,015) Mean e~/lhmpoietin concentration showed mild decrease (NS), The mean levels of proinflammatory cytokines 1I_-6, IL-8 and "INFa were slightly decreased post treatment (NS) The post treatment mean levels of IL-10 increased from 22,14 + 45,9 to 30,2 +_71,9 pg/ml (p<0,O01) The quality of life s
intravenous inflaston. Current doses of mesalamine (0 75g, rectally), sulhsalazine (lg t.id) and'or mesalamine (0.Sg t.id) were maintained, and prednisohme was tapered and stopped. Patients were assessed by tire Di~ase Activity Index, colonoscopically and histologically before and after tfiis therapy Results: Nine of the 11 patients responded to the therapy and achieved clinical and endoscopical remissions after an aw.rage of 6 weeks Two patients ,,;'ere withdrawn because of the worsening conditions and required colectomy Nine patients who completed the trial showed a significant change m the median Disease Activity index score fi'om 8 (range; 4-9) to 1 (range; 0-3) (p< 0 0 1 ) in the median colonoseopic score from 3 (range; 2-4) to 1 (range; 0-4) (p< 0.05), and in the median histological score fiom 2 (range; 1-3) to i (range; 1-2) (p< 0 0 5 ) There was no significant change in a partial thromboplastin time of these palients during this trial No serious complications were associated with this use of heparin Seven ot the nine patmnts are still in clinical remission after a median follow-up period of 4 months Conclusions: Low-dose heparin combined with 5-aminosaficylic acids proved to be a safe and usetul adjuvant therapy tbr treating patients "~vith active ulcerative cnfitis retkactory to steroid therapy A controlled study is necessary to confirm our results
T1394 Thalidomide Therapy for Pediatric Patients with Refractory Crohn's Disease Not Responding to Infliximab i%neet Gnpta, Haikaeli Andrew Barbara S Knsehner Background: Ihalidomide, a drag ruth anti-tumor necrosis tactm~alpha activity has been successfully used to treat patients with refractory Crohn's Disease (CD) including those initially responding to inlhximab Aim: To evaluate effectiveness of thalidomide as rescue therapy tor children with refi'actm'y CD who failed to respond to infliximab Methods: A computerized database at University of Chicago Children's Hospital was used to ldentit}~ children with CD who tailed infl/ximab treatment and subsequently received thalidomide rescue therapy. Six patients (4 males, mean age 16 }*ears, range 9-19 years) were given daily dose of thalidomide in an own-labeled method All had evidence of ileocofitis. Three patients also had tlstulizing Cf) (1 fleocolonie, 1 colocutaneous, and 1 rectovaginal) One patient lu~d severe gm,s~h failtu~, and one had chronic mufiifocal osteranyelitis and anemia These patients had previously tailed immunosnppressant therapy (6MP, methotrexate or tacroliruns) Pediatric Crohn's Disease Activity Index (PCDAi) and steroid dose were calculated /mfhre and afler 2 months of thalidomide treatment Resuhs were: compared using paired Student's t- test Resahs: The palients lvceived a mean of 2 3 infliximab intusions (range 14) without irnpmvement in their symptoms. They were subsequently treated wTth thalidomide (mean dose 50 rag, range 25q00 rag) for an average duration of 14 months (range 1-24 nmnths) During treatment with thalidomide, PCDAI score improved significantly (P<0 01; "Fable) Average dose of prednisone decreased fror~ 15.5 to 8 5 mg (P<0.05; Table) Of the three patients with fistulae, 2 had complete fistula closure on thalidomide and one patient had ileocecal resection betore starting thalidomide. No side etfecta usually associated ,with thalidomide (like dm*`vsiness rash or peripheral neuropathy) w'ere reported Conclusions: Pha/idomide is a safe arid effective rescue therapy for rehactory CD in children railing inflixia~ab
T1397 Parenteral Methotrexate Is Not Effective Treatment for Refractory Ulcerative Colitis Gerald M. Fraser, Ofer Ben-Bassat, Negba Segal, Michal Fishmau-Mor, Yaron Niv Background: Few treatment options other than surgeD" am available to patients with chronically active ulcerative colitis (UC) refiactory to treatment with corticosteroids and azathioprine/6-MP Previous studies peflbrmed to establish a treatment protocol tor methotrexate (MTX) have tailed to provide a consensus concerning dosage, route of administration or efficacy. Aim: To investigate the etfica{T of parenteral methotrexate in patients with re fi'actory UC Me~hods: Eight patients w~th moderate to severe refractory UC confirmed by sigmoidoscopy were treated with 25mg im MTX (and folic acid) tot 16 weeks. Bloodwork was performed weekly Seventy of disease was assessed by the Mayo Clinic score at the beginning and end of treatment Results: Five male and 3 temale patients, mean age 38 y, were recruited Median Mayo Clinic score at entry was 9 (range 7-11). Six patients had left-sided disuse, i pancolitis and 1 proctosigmoiditis. All patients had received corticosteroids and azathioprine/ 6-MP without achieving remission, and 2 had relapsed after cyclosponn-A treamrent 6/8 patients completed 16w of MTX treatment. One patient withdrew due to a severe exacerbation and 1 withdrew because of thi/nre to improve Two patients developed anemia and 1 patient hypertransammasemia The median Mayo Clinic score at 16 w was 8 (range 6-11). Two patients were referred for proctocolectomy at the end of the study Conclusion: Treatment with 25rag MTX im for 16 w was ineffective in this small group of patients with refractory UC
Responseto Thalidomidein Refrl~:toryCD failing lufliximab Before Thalidomide 2 Months aft.orThalidomide PCDAI (mean) 39.5 20 Prednisone(nlg) 15 8 Fistulae* 2 0 *3rd patentwith fistulahad surgicalresectionpriorto startingIhalidomir
T1398
P value <0.01 <0,05 ND
Long-term Patient-led Maintenance of Remission in Ulcerative Colitis with Balsalazide: Is it Effective and Safe? Jonathan R Green, Charles H Swan, john A Gibson, Graeme D Kerr, Edwin Swarbrick, Philip C Fhornton The use of a single 5-aminusalicylate (5-ASA), previously shown to be effective tbr acute relapse and maintenance of remission in ulcerative colitis (UC), could enhance and simplity longer-term management by aIIowmg the patient to decide their appropriate dose of (herapy. The efficacy and safety of this approach has not previouaIy been tested over a prolonged period. Balsalazide, a 5-ASA prodmg, was used to assess the strategy of patientded dosing m two groups of patients in remission from UC Fifty-two patients in long-term (stable) remission (SR) and 76 m recent remission (RR) were given guidelines about changes and limits of therapy and ,#ere followed prospectively tot 3 years. Assessments of symptoms, mucosa] inflammation, general ;veil-being and adverse events were made every 3 momhs with laboratory assessments every 6 months. Patients were very satisfied with this approach Analysis of the dosages used showed a wide range (1 5-6.0g/day) in both groups, but an average daily dose of balsalazide over 3 ),ears of 3.0g in both groups Relapse needing steroid therapy occurred in 23 SR patients (45%) at 3 ),ears (median time to relapse: 36 montfis) compared with 45 RR patients (59%) (median time to relapse: 22 months) Fewer patients experienced a relapse in each successive year in both groups, clitoral scores (well hemg, signs/symptonrs, underlying disease) for SR patients were consistent over 3 years while RR patients still in remission showed a slight improvement Both groups needed less dose increases as time progressed "lime since last relapse was significantly associated with relapse during the first year of treatment (p<0.033) flrr SR patients Laboratory a~lalyses showed no adverse medication-related haematologiea/ or bioci~emical changes and there was no mortality or significant morbidity (eg, need for colecmmy) in either patient group In conclusion, this long-term patient-led maintenance therapy with balsalazide appears to be well tolerated, safe and ef[?'ctive tot patients with UC
T1395 Antisense Inhibitor of ICAM4 Given as Enema Improves Symptomatic Pouehitis Philip B. Miner Jr., Barbara L Bane, Syed A, Sadiq, Joann D Bradley, Mark Wedel Backgronnd and Siguificance: The surgical constmcti~ra of an ileal pouch cmmected to the anal canal creating a comment ileomml anastamosis Ires revolutionized the treatment ot patients requiring a total colectomy tot ulcerative colitis or familial polyposis. Unfortunately, inflammation m the pouch ofleu causes symptoms of pain, urgency and bleeding as troublesome as Ihe ongmal disease Treatment of pouchitis is olden disappointing. ICAM-1 influences lymphocyte inaction, is pivotal m cell tralhcking, and is over expressed in pouchitis. ISIS 2302 is an antisense inhibitor of I(i?~M-1 Our aim was to determine if enema administration of ISiS 2302 would improve the symptom score, endo~opic appearance and pouch mucosal histology in patients with chronic pouchitis, Methods: 6 patients with chronic unremitting pouchRis with a Pouchitis Disease Activity Index (PDA1) of glvater than 7 were giwm 240 mg 15IS 2302 antisense enemas nightly for 6 weeks in an unblmded, open-label study. Clinical evaluation arid endoscopy were perfbrmed at baseline and at 3 and 6 weeks of treatment Histologlc a~essment ,*as done at baseline and 6 weeks. Results: Median PDAI (symptom score, endoscopy and histology) fell from a baselnie value of 115 (range 10 to 13) after 6 weeks (p=003). Benefit was seen in the Clinical PDAI (symptom score and endoscopy) with a median score of 8 5 (range 8 to I l) at baseline, 55 (range 1 to 8) at 3 weeks ( p = 0 03) and 3.0 (range 3 to 8) at 6 weeks (p=0.03) with rio change in histology'. Conclusion: Topically admmiatered antisense nihibition of ICAM- 1 holds promise for managing patients with chronic unremitting pouchitis
T1396
T1399
Low-dose Heparin in Active Ulcerative Colitis Refractory to Steroid Therapy Atsushi lkehata, Mitsunl Yamakawa, Takao Fujiwara, Masaki Kitagawa, Tatsuya Miura, Akihiko Murakami, Mitsum Ono~ Sadahide Ono
Effects of Rebamipide on Cytokine Production and Restitution by Epithelial Cells May Be Related to Its Clinical Efficacy in Ulcerative Colitis Patients Kenji Ina, Ryuu-hi Fnmta, Ynji Kuno Kazuo Nobata, Tomoyuki Tsuzuki, Takahlmi Ando, Kazuo Kusugami
Background: Untractionated heparin has ~ e n tound to be beneficial in the treatment ot severe ulcerative colitis. The effect of heparin was assumed to be due to a promotion of epithelial wound healing as ;*,'ell as its anticoagulant and anti-inflammatmT properties. However, it has been sometimes associated with serious bleeding complications by using of high dose without 5-aminosalicylic acid, Methods: We evaluated the efficacy and safety oflow-dose heparin combined with 5-amino~licylic acids in the treatment of active ulcerative colitis rekactory to steroid therapy Eleven patients whose condition had not improved after at least seven days of intravenous corticosteroid thenapy were included in an open-labelled tnal These patients received 5,000 units of unfi'actionated heparin daily by continuous
Background: Immunomodulatory treatment is accepted as corticostemid-sparing therapy t\)r ulcerative colitis (UC) patients Rebamipide, a cytoprotective agent, has been reported to attenuate the, inflammatory events in animal colitis models. There are preliminary reports suggesting the effectiveness of rebamipide enema therapy in UC patients, however, its precise mechanism remains unclear Methods: The anti-inflammatory potential of rebanrtpide *`vas examined by the cBanges in c}'tokine production by (he colon ic epithelial cell line, T84 cells, in vitro. Its modulatory ettiects on mucosal repair were tested using the wound model
A-525
AGA Abstracts
intravenous inflaston. Current doses of mesalamine (0 75g, rectally), sulhsalazine (lg t.id) and'or mesalamine (0.Sg t.id) were maintained, and prednisohme was tapered and stopped. Patients were assessed by tire Di~ase Activity Index, colonoscopically and histologically before and after tfiis therapy Results: Nine of the 11 patients responded to the therapy and achieved clinical and endoscopical remissions after an aw.rage of 6 weeks Two patients ,,;'ere withdrawn because of the worsening conditions and required colectomy Nine patients who completed the trial showed a significant change m the median Disease Activity index score fi'om 8 (range; 4-9) to 1 (range; 0-3) (p< 0 0 1 ) in the median colonoseopic score from 3 (range; 2-4) to 1 (range; 0-4) (p< 0.05), and in the median histological score fiom 2 (range; 1-3) to i (range; 1-2) (p< 0 0 5 ) There was no significant change in a partial thromboplastin time of these palients during this trial No serious complications were associated with this use of heparin Seven ot the nine patmnts are still in clinical remission after a median follow-up period of 4 months Conclusions: Low-dose heparin combined with 5-aminosaficylic acids proved to be a safe and usetul adjuvant therapy tbr treating patients "~vith active ulcerative cnfitis retkactory to steroid therapy A controlled study is necessary to confirm our results
T1394 Thalidomide Therapy for Pediatric Patients with Refractory Crohn's Disease Not Responding to Infliximab i%neet Gnpta, Haikaeli Andrew Barbara S Knsehner Background: Ihalidomide, a drag ruth anti-tumor necrosis tactm~alpha activity has been successfully used to treat patients with refractory Crohn's Disease (CD) including those initially responding to inlhximab Aim: To evaluate effectiveness of thalidomide as rescue therapy tor children with refi'actm'y CD who failed to respond to infliximab Methods: A computerized database at University of Chicago Children's Hospital was used to ldentit}~ children with CD who tailed infl/ximab treatment and subsequently received thalidomide rescue therapy. Six patients (4 males, mean age 16 }*ears, range 9-19 years) were given daily dose of thalidomide in an own-labeled method All had evidence of ileocofitis. Three patients also had tlstulizing Cf) (1 fleocolonie, 1 colocutaneous, and 1 rectovaginal) One patient lu~d severe gm,s~h failtu~, and one had chronic mufiifocal osteranyelitis and anemia These patients had previously tailed immunosnppressant therapy (6MP, methotrexate or tacroliruns) Pediatric Crohn's Disease Activity Index (PCDAi) and steroid dose were calculated /mfhre and afler 2 months of thalidomide treatment Resuhs were: compared using paired Student's t- test Resahs: The palients lvceived a mean of 2 3 infliximab intusions (range 14) without irnpmvement in their symptoms. They were subsequently treated wTth thalidomide (mean dose 50 rag, range 25q00 rag) for an average duration of 14 months (range 1-24 nmnths) During treatment with thalidomide, PCDAI score improved significantly (P<0 01; "Fable) Average dose of prednisone decreased fror~ 15.5 to 8 5 mg (P<0.05; Table) Of the three patients with fistulae, 2 had complete fistula closure on thalidomide and one patient had ileocecal resection betore starting thalidomide. No side etfecta usually associated ,with thalidomide (like dm*`vsiness rash or peripheral neuropathy) w'ere reported Conclusions: Pha/idomide is a safe arid effective rescue therapy for rehactory CD in children railing inflixia~ab
T1397 Parenteral Methotrexate Is Not Effective Treatment for Refractory Ulcerative Colitis Gerald M. Fraser, Ofer Ben-Bassat, Negba Segal, Michal Fishmau-Mor, Yaron Niv Background: Few treatment options other than surgeD" am available to patients with chronically active ulcerative colitis (UC) refiactory to treatment with corticosteroids and azathioprine/6-MP Previous studies peflbrmed to establish a treatment protocol tor methotrexate (MTX) have tailed to provide a consensus concerning dosage, route of administration or efficacy. Aim: To investigate the etfica{T of parenteral methotrexate in patients with re fi'actory UC Me~hods: Eight patients w~th moderate to severe refractory UC confirmed by sigmoidoscopy were treated with 25mg im MTX (and folic acid) tot 16 weeks. Bloodwork was performed weekly Seventy of disease was assessed by the Mayo Clinic score at the beginning and end of treatment Results: Five male and 3 temale patients, mean age 38 y, were recruited Median Mayo Clinic score at entry was 9 (range 7-11). Six patients had left-sided disuse, i pancolitis and 1 proctosigmoiditis. All patients had received corticosteroids and azathioprine/ 6-MP without achieving remission, and 2 had relapsed after cyclosponn-A treamrent 6/8 patients completed 16w of MTX treatment. One patient withdrew due to a severe exacerbation and 1 withdrew because of thi/nre to improve Two patients developed anemia and 1 patient hypertransammasemia The median Mayo Clinic score at 16 w was 8 (range 6-11). Two patients were referred for proctocolectomy at the end of the study Conclusion: Treatment with 25rag MTX im for 16 w was ineffective in this small group of patients with refractory UC
Responseto Thalidomidein Refrl~:toryCD failing lufliximab Before Thalidomide 2 Months aft.orThalidomide PCDAI (mean) 39.5 20 Prednisone(nlg) 15 8 Fistulae* 2 0 *3rd patentwith fistulahad surgicalresectionpriorto startingIhalidomir
T1398
P value <0.01 <0,05 ND
Long-term Patient-led Maintenance of Remission in Ulcerative Colitis with Balsalazide: Is it Effective and Safe? Jonathan R Green, Charles H Swan, john A Gibson, Graeme D Kerr, Edwin Swarbrick, Philip C Fhornton The use of a single 5-aminusalicylate (5-ASA), previously shown to be effective tbr acute relapse and maintenance of remission in ulcerative colitis (UC), could enhance and simplity longer-term management by aIIowmg the patient to decide their appropriate dose of (herapy. The efficacy and safety of this approach has not previouaIy been tested over a prolonged period. Balsalazide, a 5-ASA prodmg, was used to assess the strategy of patientded dosing m two groups of patients in remission from UC Fifty-two patients in long-term (stable) remission (SR) and 76 m recent remission (RR) were given guidelines about changes and limits of therapy and ,#ere followed prospectively tot 3 years. Assessments of symptoms, mucosa] inflammation, general ;veil-being and adverse events were made every 3 momhs with laboratory assessments every 6 months. Patients were very satisfied with this approach Analysis of the dosages used showed a wide range (1 5-6.0g/day) in both groups, but an average daily dose of balsalazide over 3 ),ears of 3.0g in both groups Relapse needing steroid therapy occurred in 23 SR patients (45%) at 3 ),ears (median time to relapse: 36 montfis) compared with 45 RR patients (59%) (median time to relapse: 22 months) Fewer patients experienced a relapse in each successive year in both groups, clitoral scores (well hemg, signs/symptonrs, underlying disease) for SR patients were consistent over 3 years while RR patients still in remission showed a slight improvement Both groups needed less dose increases as time progressed "lime since last relapse was significantly associated with relapse during the first year of treatment (p<0.033) flrr SR patients Laboratory a~lalyses showed no adverse medication-related haematologiea/ or bioci~emical changes and there was no mortality or significant morbidity (eg, need for colecmmy) in either patient group In conclusion, this long-term patient-led maintenance therapy with balsalazide appears to be well tolerated, safe and ef[?'ctive tot patients with UC
T1395 Antisense Inhibitor of ICAM4 Given as Enema Improves Symptomatic Pouehitis Philip B. Miner Jr., Barbara L Bane, Syed A, Sadiq, Joann D Bradley, Mark Wedel Backgronnd and Siguificance: The surgical constmcti~ra of an ileal pouch cmmected to the anal canal creating a comment ileomml anastamosis Ires revolutionized the treatment ot patients requiring a total colectomy tot ulcerative colitis or familial polyposis. Unfortunately, inflammation m the pouch ofleu causes symptoms of pain, urgency and bleeding as troublesome as Ihe ongmal disease Treatment of pouchitis is olden disappointing. ICAM-1 influences lymphocyte inaction, is pivotal m cell tralhcking, and is over expressed in pouchitis. ISIS 2302 is an antisense inhibitor of I(i?~M-1 Our aim was to determine if enema administration of ISiS 2302 would improve the symptom score, endo~opic appearance and pouch mucosal histology in patients with chronic pouchitis, Methods: 6 patients with chronic unremitting pouchRis with a Pouchitis Disease Activity Index (PDA1) of glvater than 7 were giwm 240 mg 15IS 2302 antisense enemas nightly for 6 weeks in an unblmded, open-label study. Clinical evaluation arid endoscopy were perfbrmed at baseline and at 3 and 6 weeks of treatment Histologlc a~essment ,*as done at baseline and 6 weeks. Results: Median PDAI (symptom score, endoscopy and histology) fell from a baselnie value of 115 (range 10 to 13) after 6 weeks (p=003). Benefit was seen in the Clinical PDAI (symptom score and endoscopy) with a median score of 8 5 (range 8 to I l) at baseline, 55 (range 1 to 8) at 3 weeks ( p = 0 03) and 3.0 (range 3 to 8) at 6 weeks (p=0.03) with rio change in histology'. Conclusion: Topically admmiatered antisense nihibition of ICAM- 1 holds promise for managing patients with chronic unremitting pouchitis
T1396
T1399
Low-dose Heparin in Active Ulcerative Colitis Refractory to Steroid Therapy Atsushi lkehata, Mitsunl Yamakawa, Takao Fujiwara, Masaki Kitagawa, Tatsuya Miura, Akihiko Murakami, Mitsum Ono~ Sadahide Ono
Effects of Rebamipide on Cytokine Production and Restitution by Epithelial Cells May Be Related to Its Clinical Efficacy in Ulcerative Colitis Patients Kenji Ina, Ryuu-hi Fnmta, Ynji Kuno Kazuo Nobata, Tomoyuki Tsuzuki, Takahlmi Ando, Kazuo Kusugami
Background: Untractionated heparin has ~ e n tound to be beneficial in the treatment ot severe ulcerative colitis. The effect of heparin was assumed to be due to a promotion of epithelial wound healing as ;*,'ell as its anticoagulant and anti-inflammatmT properties. However, it has been sometimes associated with serious bleeding complications by using of high dose without 5-aminosalicylic acid, Methods: We evaluated the efficacy and safety oflow-dose heparin combined with 5-amino~licylic acids in the treatment of active ulcerative colitis rekactory to steroid therapy Eleven patients whose condition had not improved after at least seven days of intravenous corticosteroid thenapy were included in an open-labelled tnal These patients received 5,000 units of unfi'actionated heparin daily by continuous
Background: Immunomodulatory treatment is accepted as corticostemid-sparing therapy t\)r ulcerative colitis (UC) patients Rebamipide, a cytoprotective agent, has been reported to attenuate the, inflammatory events in animal colitis models. There are preliminary reports suggesting the effectiveness of rebamipide enema therapy in UC patients, however, its precise mechanism remains unclear Methods: The anti-inflammatory potential of rebanrtpide *`vas examined by the cBanges in c}'tokine production by (he colon ic epithelial cell line, T84 cells, in vitro. Its modulatory ettiects on mucosal repair were tested using the wound model
A-525
AGA Abstracts