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Sa1906 Efficacy and Safety of Infliximab in Intestinal BehçET's Disease
AGA Abstracts
usefulness of intravenous tacrolimus in refractory ulcerative colitis, 18 patients with refractory moderately/severely active UC (steroid-refractory, n = 11; steroid-dependent, n = 7) were enrolled. Tacrolimus (0.025ng/kg body weight per a day) was initially administered intravenously with serum levels of 10 - 17ng/mL for 7 days and later switched to the oral formulation. Clinical activity index (CAI) score and Rachmilewitz's endoscopic index (EI) at 2 and 12 weeks after tacrolimus initiation was prospectively evaluated. Mean duration between administration of tacrolimus and reaching the high concentration level (>10mg/mL) in intravenous tacrolimus group was also assessed. Results: Fifteen patients (83%) experienced a clinical and laboratory response and 10 (56%) went into remission in 2 weeks. The median CAI decreased from 13.1± 0.45 at initiation to 5.1± 0.66 after 2 weeks of treatment. The median EI decreased from 10.2± 0.32 at initiation to 6.1± 0.43 after 2 weeks of treatment and 1.9± 0.62 after 12 weeks of treatment. Serum tacrolimus concentration was achieved at high level in 24 hours intravenous tacrolimus group although previous multicenter study indicated that 5.0 days was needed to achieve at same level in oral tacrolimus group (Naganuma et al, J Gatroenterol 2011). Intravenous tacrolimus therapy was well tolerated, with only minor side effects. Conclusion: Intravenous tacrolimus therapy is safe and effective for refractory UC patients. It may be useful as salvage therapy to avoid surgery. Long-term prognosis in patients with intravenous tacrolimus should be assessed in the near future.
Figure 1: Time to re-induction dose
Sa1908 Avoidance of Repeat Surgery With Endoscopic Balloon Dilatation of Anastomotic Strictures in Crohn's Disease Kavinderjit S. Nanda, William A. Courtney, Denise Keegan, Kathryn Byrne, Blathnaid Nolan, Hugh Mulcahy, Diarmuid P. O'Donoghue, Glen A. Doherty Introduction: Despite advances in medical therapy, surgery for stricturing Crohn's disease (CD) remains common. There is a high rate of postsurgical CD recurrence particularly at the anastomosis, and over 50% of these patients will require a repeat resection. Endoscopic dilatation of CD related anastomotic strictures is an alternative to surgical resection in selected patients. Aims: To evaluate the safety and efficacy following endoscopic balloon dilatation of symptomatic anastomotic strictures in a single centre cohort. Methods: A retrospective study of CD patients who underwent balloon dilatation identified from a prospectively maintained database of 2,700 IBD patients attending a single academic centre was performed. Endoscopic balloon dilatation was performed with a controlled radial expansion (CRE) balloon (typically 15-18mm) under endoscopic vision with or without fluoroscopic guidance. Results: 53 procedures were performed on 31 patients (F= 14, M= 17). 55% were smokers. Primary surgical procedures were; right hemicolectomy/ileocaecal resection (n=23), colectomy with ileorectal anastomosis (n=6) and sigmoid colectomy with colon-colon anastomosis (n=2). 18% of patients were not on any medications at the time of first dilatation. Immunomodulator use, biologic agent, budesonide and 5 Aminosalicylate use was 41%, 8%, 3% and 30% respectively. Median follow up period was 46 months (IQR 14-62). Median time from initial surgery with anastomosis to stricture dilatation was 9 years (IQR 2-29). Median time from 1st dilatation to repeat surgery was 14.5 months (IQR 3-28 months). Median time from 1st dilatation to repeat dilatation was 13 months (IQR 4-60). 3/31 patients failed initial dilatation and required surgery <30 days. 28/31 (90%) patients had successful initial dilatation and no complications occurred. Of the 28 successful dilatations, 6 (21%) avoided further dilatations or surgery in the follow-up period. Stricture recurrence was detected in n=22 patients, of which 7 (25%) went straight for surgery and 15 (54%) patients had repeat dilatations. 8 (28%) patients required multiple dilatations of the stricture only (median dilatations=2 range 2-6) and 7 (25%) eventually needed surgery despite repeat dilatations. There were no complications related to dilatation. There was no difference in immunomodulator (IMD) use, biologics use and smoking status between the groups requiring surgery versus non surgical management. Conclusion: Endoscopic balloon dilatation of anastomotic strictures is safe and effective in providing symptomatic relief in CD patients with anastomotic strictures. 45% of patients show a sustained response to single/serial balloon dilatation with avoidance of further surgical resection for a median interval of 46 months. Neither medical therapy afterwards nor smoking status predicts recurrent dilatation or surgery.
Figure 2: Time to dose increase Sa1906 Efficacy and Safety of Infliximab in Intestinal BehçET's Disease Hiroto Kinoshita, Reiko Kunisaki, Hisae Yamamoto, Reikei Matsuda, Machiko Nakatogawa, Hideaki Kimura, Katsuaki Tanaka, Shin Maeda Background and aims; Intestinal Behçet's disease (BD) is characterized by intestinal inflammation with round and oval ulcers associated with serious comorbidity, such as GI bleeding and perforation. Although high doses of corticosteroids and immunosuppressants are used for treatment, refractory intestinal BD is difficult to manage. Furthermore, treatment of BD is dictated by the type of organ system involved, and a certain treatment for one specific organ manifestation can cause other organ involvements of BD. We investigated the shortand long-term efficacy and safety of infliximab (IFx) in patients with intestinal BD. Methods; Data were obtained using a retrospective chart review of 39 consecutive patients with intestinal BD from a single center in Japan. Diagnosis of intestinal BD was made according to the classification of Behçet's Disease Research Committee of Japan. Patients were considered for treatment with induction and maintenance IFx therapy after failing other recognized intestinal BD therapies. Demographics, clinical details, laboratory data, and endoscopic findings were collected for patients with intestinal BD who received at least one dose of IFx. Clinical response was evaluated 8 and 54 weeks after the initiation of IFx. We also assessed steroid-sparing effect, improvement of endoscopic findings and predictive factors of response to IFx treatment. Results; A total of 14 patients (7 males) with intestinal BD were treated with IFx between 2005 and 2011. The median age at diagnosis of intestinal BD was 43 years (range 16 to 61) and median follow-up duration after initial infliximab infusion was 46 months (range 2 to 76). One (7 %) patient had complete type, 11 (79 %) had incomplete type, and 2 (14 %) had suspected type disease. Four patients (29 %) were treated for fulminant intesdinal BD and 9 (64 %) were treated for refractory intestinal BD. Short term response at week 8 was achieved in 11 / 14 (79 %) patients. Seven of 11 (64 %) patients remained responders at week 54. Colonoscopy was performed in 6 responders, and endoscopic improvement was observed in 5 cases. Two of 3 non-responders required surgery, and the other was treated with high dose corticosteroid. Steroid reduction was possible in all of 4 responders out of 6 cases who were on steroid therapy at the time of initiation of IFx. Fulminant disease can be a negative predictor for response at weeks 8 and 54 (P < 0.05). The adverse events leading to cessation of IFx were an infusion reaction in one patient and drug-induced fever in another patient. No other organ involvements of BD were identified during the observation period. Conclusion; IFx is a well-tolerated and effective therapy for fulminant and refractory intestinal BD.
Sa1909 Accelerated Induction Therapy With Infliximab as a Rescue Treatment in Acute Severe Steroid Refractory Colitis Kavinderjit S. Nanda, William A. Courtney, Denise Keegan, Kathryn Byrne, Blathnaid Nolan, Hugh Mulcahy, Glen A. Doherty Introduction: Cyclosporin (CYA) and Infliximab (IFX) are well recognized rescue therapies for acute severe colitis. There is ongoing debate as to which therapy is associated with improved outcomes in the literature, with retrospective data suggesting better early response with CYA. Standard IFX induction therapy involves dosing intervals at weeks 0, 2 and 6. We hypothesized that accelerated induction therapy (AIT) with IFX at shorter intervals may improve outcomes. Aims: To assess the outcomes following accelerated IFX induction therapy in patients with acute severe colitis. Methods: We performed a retrospective review of a prospectively maintained IBD database of 2700 patients. Patients who presented with acute severe steroid refractory colitis and received IFX in an accelerated dosing regimen were identified. Outcomes following rescue therapy were investigated. Results: From 2010 to 2011, 8 patients (5 female) in total received AIT for steroid refractory acute colitis. N=6 had UC and n=2 had an indeterminate colitis. Mean age at therapy was 46.1 years (IQR 31-66) years). The dosing regimen was 5mg/kg IV infusion. 1 patient received a higher loading dose of 10mg/kg infusion. First infusion was at week 0, second dose at week 1 (5 to 7 days) and third dose between week 2-5. 50% were first presentations with acute colitis. All (n=8) were hospitalized and received IV steroids. The median length of hospital admission was 13 days (IQR 8-26 days). 2/8 patients did not show adequate response and eventually underwent subtotal colectomies within 30 days of presentation. Both were first time presenters. 6/8 (75%) have avoided colectomy with follow up, median duration 6.5 months (IQR 5-12 months). 4/8 (50%) have had excellent response to the loading regimen and achieved sustained response to IFX, however 2/6 (33%) showed only partial response to AIT and continue to have some ongoing symptoms. All 6 patients are on IFX maintenance therapy and 5/6 patients are concomitantly on thiopurines. There were no complications related to
Sa1907 Intravenous Tacrolimus Therapy Can Rapidly Induce Remission in Refractory Ulcerative Colitis Toshimitsu Fujii, Makoto Naganuma, Eiko Saito, Masakazu Nagahori, Mamoru Watanabe Introduction: Oral tacrolimus therapy has been reported to be effective for refractory ulcerative colitis (UC). Some reviews demonstrated that tacrolimus is superior to ciclosporin A (CyA) in improving graft survival and preventing acute rejection after transplantation. But indeed, some severely active UC patients treated with oral tacrolimus couldn't avoid total colectomy. We thought that it takes long time to achieve high trough concentration by oral administration so the treatment doesn't have effect rapidly and cannot arrest the disease progress. There has been no report to prospectively evaluate the efficacy of tacrolimus intravenous therapy in refractory ulcerative colitis. Aims and Methods: To evaluate the
AGA Abstracts
S-356
usefulness of intravenous tacrolimus in refractory ulcerative colitis, 18 patients with refractory moderately/severely active UC (steroid-refractory, n = 11; steroid-dependent, n = 7) were enrolled. Tacrolimus (0.025ng/kg body weight per a day) was initially administered intravenously with serum levels of 10 - 17ng/mL for 7 days and later switched to the oral formulation. Clinical activity index (CAI) score and Rachmilewitz's endoscopic index (EI) at 2 and 12 weeks after tacrolimus initiation was prospectively evaluated. Mean duration between administration of tacrolimus and reaching the high concentration level (>10mg/mL) in intravenous tacrolimus group was also assessed. Results: Fifteen patients (83%) experienced a clinical and laboratory response and 10 (56%) went into remission in 2 weeks. The median CAI decreased from 13.1± 0.45 at initiation to 5.1± 0.66 after 2 weeks of treatment. The median EI decreased from 10.2± 0.32 at initiation to 6.1± 0.43 after 2 weeks of treatment and 1.9± 0.62 after 12 weeks of treatment. Serum tacrolimus concentration was achieved at high level in 24 hours intravenous tacrolimus group although previous multicenter study indicated that 5.0 days was needed to achieve at same level in oral tacrolimus group (Naganuma et al, J Gatroenterol 2011). Intravenous tacrolimus therapy was well tolerated, with only minor side effects. Conclusion: Intravenous tacrolimus therapy is safe and effective for refractory UC patients. It may be useful as salvage therapy to avoid surgery. Long-term prognosis in patients with intravenous tacrolimus should be assessed in the near future.
Figure 1: Time to re-induction dose
Sa1908 Avoidance of Repeat Surgery With Endoscopic Balloon Dilatation of Anastomotic Strictures in Crohn's Disease Kavinderjit S. Nanda, William A. Courtney, Denise Keegan, Kathryn Byrne, Blathnaid Nolan, Hugh Mulcahy, Diarmuid P. O'Donoghue, Glen A. Doherty Introduction: Despite advances in medical therapy, surgery for stricturing Crohn's disease (CD) remains common. There is a high rate of postsurgical CD recurrence particularly at the anastomosis, and over 50% of these patients will require a repeat resection. Endoscopic dilatation of CD related anastomotic strictures is an alternative to surgical resection in selected patients. Aims: To evaluate the safety and efficacy following endoscopic balloon dilatation of symptomatic anastomotic strictures in a single centre cohort. Methods: A retrospective study of CD patients who underwent balloon dilatation identified from a prospectively maintained database of 2,700 IBD patients attending a single academic centre was performed. Endoscopic balloon dilatation was performed with a controlled radial expansion (CRE) balloon (typically 15-18mm) under endoscopic vision with or without fluoroscopic guidance. Results: 53 procedures were performed on 31 patients (F= 14, M= 17). 55% were smokers. Primary surgical procedures were; right hemicolectomy/ileocaecal resection (n=23), colectomy with ileorectal anastomosis (n=6) and sigmoid colectomy with colon-colon anastomosis (n=2). 18% of patients were not on any medications at the time of first dilatation. Immunomodulator use, biologic agent, budesonide and 5 Aminosalicylate use was 41%, 8%, 3% and 30% respectively. Median follow up period was 46 months (IQR 14-62). Median time from initial surgery with anastomosis to stricture dilatation was 9 years (IQR 2-29). Median time from 1st dilatation to repeat surgery was 14.5 months (IQR 3-28 months). Median time from 1st dilatation to repeat dilatation was 13 months (IQR 4-60). 3/31 patients failed initial dilatation and required surgery <30 days. 28/31 (90%) patients had successful initial dilatation and no complications occurred. Of the 28 successful dilatations, 6 (21%) avoided further dilatations or surgery in the follow-up period. Stricture recurrence was detected in n=22 patients, of which 7 (25%) went straight for surgery and 15 (54%) patients had repeat dilatations. 8 (28%) patients required multiple dilatations of the stricture only (median dilatations=2 range 2-6) and 7 (25%) eventually needed surgery despite repeat dilatations. There were no complications related to dilatation. There was no difference in immunomodulator (IMD) use, biologics use and smoking status between the groups requiring surgery versus non surgical management. Conclusion: Endoscopic balloon dilatation of anastomotic strictures is safe and effective in providing symptomatic relief in CD patients with anastomotic strictures. 45% of patients show a sustained response to single/serial balloon dilatation with avoidance of further surgical resection for a median interval of 46 months. Neither medical therapy afterwards nor smoking status predicts recurrent dilatation or surgery.
Figure 2: Time to dose increase Sa1906 Efficacy and Safety of Infliximab in Intestinal BehçET's Disease Hiroto Kinoshita, Reiko Kunisaki, Hisae Yamamoto, Reikei Matsuda, Machiko Nakatogawa, Hideaki Kimura, Katsuaki Tanaka, Shin Maeda Background and aims; Intestinal Behçet's disease (BD) is characterized by intestinal inflammation with round and oval ulcers associated with serious comorbidity, such as GI bleeding and perforation. Although high doses of corticosteroids and immunosuppressants are used for treatment, refractory intestinal BD is difficult to manage. Furthermore, treatment of BD is dictated by the type of organ system involved, and a certain treatment for one specific organ manifestation can cause other organ involvements of BD. We investigated the shortand long-term efficacy and safety of infliximab (IFx) in patients with intestinal BD. Methods; Data were obtained using a retrospective chart review of 39 consecutive patients with intestinal BD from a single center in Japan. Diagnosis of intestinal BD was made according to the classification of Behçet's Disease Research Committee of Japan. Patients were considered for treatment with induction and maintenance IFx therapy after failing other recognized intestinal BD therapies. Demographics, clinical details, laboratory data, and endoscopic findings were collected for patients with intestinal BD who received at least one dose of IFx. Clinical response was evaluated 8 and 54 weeks after the initiation of IFx. We also assessed steroid-sparing effect, improvement of endoscopic findings and predictive factors of response to IFx treatment. Results; A total of 14 patients (7 males) with intestinal BD were treated with IFx between 2005 and 2011. The median age at diagnosis of intestinal BD was 43 years (range 16 to 61) and median follow-up duration after initial infliximab infusion was 46 months (range 2 to 76). One (7 %) patient had complete type, 11 (79 %) had incomplete type, and 2 (14 %) had suspected type disease. Four patients (29 %) were treated for fulminant intesdinal BD and 9 (64 %) were treated for refractory intestinal BD. Short term response at week 8 was achieved in 11 / 14 (79 %) patients. Seven of 11 (64 %) patients remained responders at week 54. Colonoscopy was performed in 6 responders, and endoscopic improvement was observed in 5 cases. Two of 3 non-responders required surgery, and the other was treated with high dose corticosteroid. Steroid reduction was possible in all of 4 responders out of 6 cases who were on steroid therapy at the time of initiation of IFx. Fulminant disease can be a negative predictor for response at weeks 8 and 54 (P < 0.05). The adverse events leading to cessation of IFx were an infusion reaction in one patient and drug-induced fever in another patient. No other organ involvements of BD were identified during the observation period. Conclusion; IFx is a well-tolerated and effective therapy for fulminant and refractory intestinal BD.
Sa1909 Accelerated Induction Therapy With Infliximab as a Rescue Treatment in Acute Severe Steroid Refractory Colitis Kavinderjit S. Nanda, William A. Courtney, Denise Keegan, Kathryn Byrne, Blathnaid Nolan, Hugh Mulcahy, Glen A. Doherty Introduction: Cyclosporin (CYA) and Infliximab (IFX) are well recognized rescue therapies for acute severe colitis. There is ongoing debate as to which therapy is associated with improved outcomes in the literature, with retrospective data suggesting better early response with CYA. Standard IFX induction therapy involves dosing intervals at weeks 0, 2 and 6. We hypothesized that accelerated induction therapy (AIT) with IFX at shorter intervals may improve outcomes. Aims: To assess the outcomes following accelerated IFX induction therapy in patients with acute severe colitis. Methods: We performed a retrospective review of a prospectively maintained IBD database of 2700 patients. Patients who presented with acute severe steroid refractory colitis and received IFX in an accelerated dosing regimen were identified. Outcomes following rescue therapy were investigated. Results: From 2010 to 2011, 8 patients (5 female) in total received AIT for steroid refractory acute colitis. N=6 had UC and n=2 had an indeterminate colitis. Mean age at therapy was 46.1 years (IQR 31-66) years). The dosing regimen was 5mg/kg IV infusion. 1 patient received a higher loading dose of 10mg/kg infusion. First infusion was at week 0, second dose at week 1 (5 to 7 days) and third dose between week 2-5. 50% were first presentations with acute colitis. All (n=8) were hospitalized and received IV steroids. The median length of hospital admission was 13 days (IQR 8-26 days). 2/8 patients did not show adequate response and eventually underwent subtotal colectomies within 30 days of presentation. Both were first time presenters. 6/8 (75%) have avoided colectomy with follow up, median duration 6.5 months (IQR 5-12 months). 4/8 (50%) have had excellent response to the loading regimen and achieved sustained response to IFX, however 2/6 (33%) showed only partial response to AIT and continue to have some ongoing symptoms. All 6 patients are on IFX maintenance therapy and 5/6 patients are concomitantly on thiopurines. There were no complications related to
Sa1907 Intravenous Tacrolimus Therapy Can Rapidly Induce Remission in Refractory Ulcerative Colitis Toshimitsu Fujii, Makoto Naganuma, Eiko Saito, Masakazu Nagahori, Mamoru Watanabe Introduction: Oral tacrolimus therapy has been reported to be effective for refractory ulcerative colitis (UC). Some reviews demonstrated that tacrolimus is superior to ciclosporin A (CyA) in improving graft survival and preventing acute rejection after transplantation. But indeed, some severely active UC patients treated with oral tacrolimus couldn't avoid total colectomy. We thought that it takes long time to achieve high trough concentration by oral administration so the treatment doesn't have effect rapidly and cannot arrest the disease progress. There has been no report to prospectively evaluate the efficacy of tacrolimus intravenous therapy in refractory ulcerative colitis. Aims and Methods: To evaluate the
AGA Abstracts
S-356