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2-Year maintenance treatment of ileocecal Crohn’s disease with budesonide capsules or prednisolone: which patients are eligible?
S252
Abstracts
AJG – Vol. 98, No. 9, Suppl., 2003
759 2-YEAR MAINTENANCE TREATMENT OF ILEOCECAL CROHN’S DISEASE WITH BUDESONIDE CAPSULES OR PREDNISOLONE: WHICH PATIENTS ARE ELIGIBLE? R. W. Stockbrugger, M.D.*, E. Schoon, M.D., S. Bollani, M.D., T. Persson, Ph.D., L. Hapten-White, R.N., M. Vatn, M.D., G. Bianchi-Porro, M.D. University Hospital Maastricht, Maastricht, Netherlands; University Hospital L. Sacco, Milan, Italy; Rikshospitalet, Oslo, Norway and AstraZeneca R & D, Lund, Sweden. Purpose: Although frequently practiced, maintenance treatment of Crohn’s disease (CD) with systemic glucocorticosteroids (GCS) is not well accepted due to concerns about associated side effects. In the recently published MATRIX study (Gastroenterology 2003; 124:Suppl 1, A-26), budesonide (BUD) was as effective as prednisolone (PRED) in the management of ileocecal CD, but with significantly less adverse effects in general and on bone matrix in particular. The purpose of this study was to explore the characteristics of patients maintained on GCS for the 2 year study. Methods: In a multinational trial, 181 presently steroid-free patients with mild to moderate CD (98 steroid-naı¨ve [STN]; 83 with previous steroid treatment [STP]) and 90 steroid-dependent patients with stable CD (STD) were randomized to PRED 0 – 40 mg or BUD capsules 0 - 9 mg daily in a dose-adapting manner for 24 months. Characteristics of patients completing (maintaining remission of CD) and those not completing the study (failure to remain in quiescent state and/or severe side effects) were evaluated. Results: At 24 months, 136/271 patients (49% BUD, 51% PRED) remained in the study. Characteristic Male gender Age Stratum STN STP STD Disease duration Previous resection Lifetime steroids On 5-ASA On azathioprine CDAI at start ESR at start IBDQ at start
Completers
Non-completers
P-value
56% 36.2
41% 37.5
.018 .380 .980
37% 30% 33% 8.5 33% 5685 64% 13% 185 23 150
36% 31% 33% 9.1 32% 5016 55% 25% 219 30 139
.520 .830 .630 .120 .013 .001 .008 .003
Reasons for not completing were similar for patients treated with BUD or PRED. In completers, CDAI decreased with BUD from 191 to 116 and with PRED from 180 to 135 (NS). BUD completers had less treatment-emergent GCS side effects than those on PRED (P ⫽ .041).
Conclusions: Fifty percent of patients with CD were kept in remission over 2 years with BUD or PRED doses adapted to disease activity. Factors positively influencing success of maintenance treatment were male gender, mild to moderate disease activity, acceptable IBDQ. In maintenance treatment of CD, BUD is preferable to PRED as it causes less GCS-related side effects at equal efficacy. 760 ARE GASTROENTEROLOGISTS OPTIMIZING THERAPY IN IBD? Sarathchandra I. Reddy, M.D., Sonia Friedman, M.D., Lisa L. Strate, M.D., Jennifer J. Telford, M.D., Peter A. Banks, M.D.*. Brigham and Women’s Hospital, Boston, MA. Purpose: Guidelines have been published outlining the optimal therapy of patients with inflammatory bowel disease (IBD). The purpose of this study was to determine whether patients referred for a second opinion were receiving optimal therapy for IBD.
Methods: Patients with IBD who were referred by a gastroenterologist for a second opinion to Brigham and Women’s Hospital between January 2001 and April 2003 were enrolled in this study. Patients who were referred by non-gastroenterologists were excluded. Clinical information was obtained by direct patient interview at the time of initial patient visit as well as by a review of prior clinical, radiologic, and pathologic records. Data included the diagnosis, clinical symptoms, prior medical therapy, dosage of maintenance medications, use of steroid-sparing medications, and preventive measures for metabolic bone disease. Results: The study population consisted of 64 consecutive patients: 18 with ulcerative colitis, 44 with Crohn’s disease, and 2 in whom the original diagnosis of IBD could not be confirmed. Of the 62 patients with confirmed inflammatory bowel disease, 53 patients had symptoms of active disease and 9 patients were asymptomatic on their present medical regimen. All subsequent analyses were carried out on the 53 patients with active disease. Of 38 patients treated with aminosalicylates, 24 (63%) were not receiving maximal doses. Of 28 patients treated with oral corticosteroids within 6 months of their clinic visit, 21 (75%) patients had been treated for greater than 3 months. In 12/21 (57%) there was no attempt to start steroid-sparing medications such as 6-mercaptopurine (6MP), azathioprine, or infliximab; in 17/21 (81%) there were inadequate measures to prevent or monitor metabolic bone disease by medications or bone mineral density scan. Of 7 patients treated with either 6MP or azathioprine, 6 (86%) were suboptimally dosed (less than 1.0 mg/kg of 6MP or less than 2.0 mg/kg of azathioprine) without an attempt to increase dosage. Overall, only 14/53 (26%) had ever been treated with 6MP or azathioprine. Conclusions: Gastroenterologists often fail to optimize medical therapy in patients with active symptoms of inflammatory bowel disease. In particular, there is suboptimal dosing of medications, underutilization of steroidsparing agents, and inadequate attention to metabolic bone disease.
761 INFLIXIMAB TREATMENT FOR CROHN’S DISEASE TREATED WITH ELEMENTAL DIET: THE TOKYO EXPERIENCE Torao Tanaka, M.D., Masakazu Takazoe, M.D.*, Eijirou Morita, M.D., Fumitaka Terabe, M.D. Social Insuarance Medical Center, Tokyo, Japan. Purpose: The efficacy and safety of infliximab for CD have been shown in western countries. In Japan, the prevalence of CD is increasing approximately 15% per year and elemental diet has been the first line therapy for CD from 1980s. Recently, infliximab was registered in Japan (May 2002). In this setting, we report our experience with the use of infliximab in patients with refractory luminal (L) or fistulizing (F) CD. Methods: We followed 61 consecutive patients with refractory CD (ineffective therapy with ⬎900 kcal elemental diet or ⬎10mg predonisone) and a CDAI from 222– 428 who treated with infliximab between July 2002 and May 2003. Patients received Infliximab (5mg/kg) at week 0 only (L: 43pts) or at weeks 0,2,6 (F 18pts) and prospectively monitored. The assessment was based on Harvey-Bradshaw Index for luminal disease (L) and the closure of fistulas for fistulizing disease (F). Results: Initial infusion course response and remission rate at 4 weeks was 89% and 63% in L, 78% and 32% in F respectively. Patients received one to five infusions of infliximab and followed for a median of 25 weeks (range 3 to 52). The median duration of response was 14 weeks (range 5 to 44 weeks). Relapse occurred in 72% of at mean 11.2 weeks L and in 55% at a mean of 18 weeks F. Patients concurrently treated with elementary diet (⬎900 kcal/day) had longer times to relapse (4.1 mo vs. 2.1mo) compared to patients treated with infliximab alone but did not reach to significance. Adverse events were seen in up 8 patients (12%). These events were characterized mild, except in one patient who had a treatable severe headache and anaphylactic-like infusion reaction was not observed. Conclusions: The patient group in the present study realized significant clinical benefit, with minimal adverse effect, following treatment of Inflix-
Abstracts
AJG – Vol. 98, No. 9, Suppl., 2003
759 2-YEAR MAINTENANCE TREATMENT OF ILEOCECAL CROHN’S DISEASE WITH BUDESONIDE CAPSULES OR PREDNISOLONE: WHICH PATIENTS ARE ELIGIBLE? R. W. Stockbrugger, M.D.*, E. Schoon, M.D., S. Bollani, M.D., T. Persson, Ph.D., L. Hapten-White, R.N., M. Vatn, M.D., G. Bianchi-Porro, M.D. University Hospital Maastricht, Maastricht, Netherlands; University Hospital L. Sacco, Milan, Italy; Rikshospitalet, Oslo, Norway and AstraZeneca R & D, Lund, Sweden. Purpose: Although frequently practiced, maintenance treatment of Crohn’s disease (CD) with systemic glucocorticosteroids (GCS) is not well accepted due to concerns about associated side effects. In the recently published MATRIX study (Gastroenterology 2003; 124:Suppl 1, A-26), budesonide (BUD) was as effective as prednisolone (PRED) in the management of ileocecal CD, but with significantly less adverse effects in general and on bone matrix in particular. The purpose of this study was to explore the characteristics of patients maintained on GCS for the 2 year study. Methods: In a multinational trial, 181 presently steroid-free patients with mild to moderate CD (98 steroid-naı¨ve [STN]; 83 with previous steroid treatment [STP]) and 90 steroid-dependent patients with stable CD (STD) were randomized to PRED 0 – 40 mg or BUD capsules 0 - 9 mg daily in a dose-adapting manner for 24 months. Characteristics of patients completing (maintaining remission of CD) and those not completing the study (failure to remain in quiescent state and/or severe side effects) were evaluated. Results: At 24 months, 136/271 patients (49% BUD, 51% PRED) remained in the study. Characteristic Male gender Age Stratum STN STP STD Disease duration Previous resection Lifetime steroids On 5-ASA On azathioprine CDAI at start ESR at start IBDQ at start
Completers
Non-completers
P-value
56% 36.2
41% 37.5
.018 .380 .980
37% 30% 33% 8.5 33% 5685 64% 13% 185 23 150
36% 31% 33% 9.1 32% 5016 55% 25% 219 30 139
.520 .830 .630 .120 .013 .001 .008 .003
Reasons for not completing were similar for patients treated with BUD or PRED. In completers, CDAI decreased with BUD from 191 to 116 and with PRED from 180 to 135 (NS). BUD completers had less treatment-emergent GCS side effects than those on PRED (P ⫽ .041).
Conclusions: Fifty percent of patients with CD were kept in remission over 2 years with BUD or PRED doses adapted to disease activity. Factors positively influencing success of maintenance treatment were male gender, mild to moderate disease activity, acceptable IBDQ. In maintenance treatment of CD, BUD is preferable to PRED as it causes less GCS-related side effects at equal efficacy. 760 ARE GASTROENTEROLOGISTS OPTIMIZING THERAPY IN IBD? Sarathchandra I. Reddy, M.D., Sonia Friedman, M.D., Lisa L. Strate, M.D., Jennifer J. Telford, M.D., Peter A. Banks, M.D.*. Brigham and Women’s Hospital, Boston, MA. Purpose: Guidelines have been published outlining the optimal therapy of patients with inflammatory bowel disease (IBD). The purpose of this study was to determine whether patients referred for a second opinion were receiving optimal therapy for IBD.
Methods: Patients with IBD who were referred by a gastroenterologist for a second opinion to Brigham and Women’s Hospital between January 2001 and April 2003 were enrolled in this study. Patients who were referred by non-gastroenterologists were excluded. Clinical information was obtained by direct patient interview at the time of initial patient visit as well as by a review of prior clinical, radiologic, and pathologic records. Data included the diagnosis, clinical symptoms, prior medical therapy, dosage of maintenance medications, use of steroid-sparing medications, and preventive measures for metabolic bone disease. Results: The study population consisted of 64 consecutive patients: 18 with ulcerative colitis, 44 with Crohn’s disease, and 2 in whom the original diagnosis of IBD could not be confirmed. Of the 62 patients with confirmed inflammatory bowel disease, 53 patients had symptoms of active disease and 9 patients were asymptomatic on their present medical regimen. All subsequent analyses were carried out on the 53 patients with active disease. Of 38 patients treated with aminosalicylates, 24 (63%) were not receiving maximal doses. Of 28 patients treated with oral corticosteroids within 6 months of their clinic visit, 21 (75%) patients had been treated for greater than 3 months. In 12/21 (57%) there was no attempt to start steroid-sparing medications such as 6-mercaptopurine (6MP), azathioprine, or infliximab; in 17/21 (81%) there were inadequate measures to prevent or monitor metabolic bone disease by medications or bone mineral density scan. Of 7 patients treated with either 6MP or azathioprine, 6 (86%) were suboptimally dosed (less than 1.0 mg/kg of 6MP or less than 2.0 mg/kg of azathioprine) without an attempt to increase dosage. Overall, only 14/53 (26%) had ever been treated with 6MP or azathioprine. Conclusions: Gastroenterologists often fail to optimize medical therapy in patients with active symptoms of inflammatory bowel disease. In particular, there is suboptimal dosing of medications, underutilization of steroidsparing agents, and inadequate attention to metabolic bone disease.
761 INFLIXIMAB TREATMENT FOR CROHN’S DISEASE TREATED WITH ELEMENTAL DIET: THE TOKYO EXPERIENCE Torao Tanaka, M.D., Masakazu Takazoe, M.D.*, Eijirou Morita, M.D., Fumitaka Terabe, M.D. Social Insuarance Medical Center, Tokyo, Japan. Purpose: The efficacy and safety of infliximab for CD have been shown in western countries. In Japan, the prevalence of CD is increasing approximately 15% per year and elemental diet has been the first line therapy for CD from 1980s. Recently, infliximab was registered in Japan (May 2002). In this setting, we report our experience with the use of infliximab in patients with refractory luminal (L) or fistulizing (F) CD. Methods: We followed 61 consecutive patients with refractory CD (ineffective therapy with ⬎900 kcal elemental diet or ⬎10mg predonisone) and a CDAI from 222– 428 who treated with infliximab between July 2002 and May 2003. Patients received Infliximab (5mg/kg) at week 0 only (L: 43pts) or at weeks 0,2,6 (F 18pts) and prospectively monitored. The assessment was based on Harvey-Bradshaw Index for luminal disease (L) and the closure of fistulas for fistulizing disease (F). Results: Initial infusion course response and remission rate at 4 weeks was 89% and 63% in L, 78% and 32% in F respectively. Patients received one to five infusions of infliximab and followed for a median of 25 weeks (range 3 to 52). The median duration of response was 14 weeks (range 5 to 44 weeks). Relapse occurred in 72% of at mean 11.2 weeks L and in 55% at a mean of 18 weeks F. Patients concurrently treated with elementary diet (⬎900 kcal/day) had longer times to relapse (4.1 mo vs. 2.1mo) compared to patients treated with infliximab alone but did not reach to significance. Adverse events were seen in up 8 patients (12%). These events were characterized mild, except in one patient who had a treatable severe headache and anaphylactic-like infusion reaction was not observed. Conclusions: The patient group in the present study realized significant clinical benefit, with minimal adverse effect, following treatment of Inflix-