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Su1205 Long-Term Outcome of Treatment With Infliximab in Patients With Steroid-Dependent Ulcerative Colitis
Su1205
AGA Abstracts
Long-Term Outcome of Treatment With Infliximab in Patients With SteroidDependent Ulcerative Colitis Alessandro Armuzzi, Daniela Pugliese, Silvio Danese, Gianluca Rizzo, Manuela Marzo, Carla Felice, Gianluca Andrisani, Gionata Fiorino, Olga Maria Nardone, Italo De Vitis, Alfredo Papa, Gian Ludovico Rapaccini, Luisa Guidi Background & Aims: Up to 40% of ulcerative colitis (UC) patients need steroids during their course and 20% of them become steroid-dependent. Thiopurines are recommended in steroid-dependent UC, but their efficacy is debated. We recently reported more than 30% of steroid-free clinical remission and mucosal healing for UC patients after 1 year of infliximab (IFX) treatment1. Aims of our study were to describe the long-term outcome of IFX treatment in active steroid-dependent UC and to investigate if predictors of sustained clinical response and colectomy could be identified. Methods: Consecutive patients with active steroid-dependent UC treated with IFX were studied. Co-primary outcomes were 1) sustained clinical response in patients who achieved clinical remission (no diarrhoea, no blood) or response (clinical improvement, despite persistent blood loss) after induction and 2) colectomy free-survival. Sustained clinical response was defined as a persistent clinical improvement during the follow-up, without need of a new course of steroids. Results: 126 steroid-dependent UC patients were included. 45% of them were Naïve to thiopurines and 56% were started on concomitant thiopurines. The median duration of follow-up was 32 months (IQR 22-62), with a median number of infusion per patient of 14 (IQR 7-24). The colectomy rate was 23% (29/126), with a median time to colectomy of 16 months (IQR 930). After induction, 77% (97/126) of patients achieved clinical benefit. Among them, 47% (46/97) had a sustained clinical response during follow-up. 88 of 126 patients were on steroids at enrolment (daily median equivalent of prednisone dose: 25 mg, IQR 15-30) and 46% (41/88) withdrew steroids during long-term IFX treatment. Cox regression identified the Mayo endoscopic score ≥2 at baseline (p=0.03, HR 2.7, 95%CI 1.1-6.9) and high Creactive protein (CRP) after induction (p=0.001, HR 5.5, 95%CI 1.9-15) as independent predictors of colectomy. Thiopurine Naïve status (p=0.03, HR 0.35, 95%CI 0.1-0.9) was protective from colectomy. Combination therapy of IFX and thiopurines (p ,0.0001, HR 6.2, 95%CI 2.6-14) was identified as independent predictor of sustained clinical response. Serious adverse events leading to IFX withdrawal were recorded in 11.1% of patients. Conclusions: Infliximab long-term treatment is effective in this large cohort of steroiddependent UC patients. The severity of endoscopic lesions at baseline and a persistently high CRP after induction are associated with higher rates of colectomy. Conversely, thiopurine Naïve status is protective from colectomy. Combination therapy is predictive of sustained clinical response. 1) Armuzzi A, et al. Gastroenterology 2012;142(Suppl. 1):S205; Inflamm Bowel Dis 2012: in press.
Su1207 Relation Between Mucosal Healing and Long-Term Outcomes in Patients With Ulcerative Colitis Kaoru Yokoyama, Kiyonori Kobayashi, Miyuki Mukae, Miwa Sada, Wasaburo Koizumi Objectives: Mucosal healing is considered an important factor in the assessment of therapeutic effectiveness and treatment goals in inflammatory bowel disease. However, long-term studies of whether mucosal healing contributes to remission maintenance remain inadequate. We performed colonoscopy in patients with ulcerative colitis (UC) who had clinical remission to clarify the relation between endoscopic findings and outcomes. Subjects and Methods: We studied 47 patients with UC in clinical remission as confirmed by total colonoscopy between January 2005 and December 2006 who were subsequently followed up for 5 years. At the initial attack, the extent of UC was pancolitis in 13 patients (28%), left-sided colitis in 14 (30%), proctitis in 12 (26%), and unknown in 8 (17%) who were transferred from other hospitals. The Mayo score was used to assess clinical response. Clinical remission was defined as a score of 0 for both daily stool frequency and bloody stools. Flare-ups were defined as the need to use additional drugs or to alter the treatment regimen. Endoscopic findings were evaluated according to the Mayo endoscopic subscore classification (0: normal or inactive disease, 1: erythema, decreased vascular pattern, 2: marked erythema, absent vascular pattern, friability, erosions, and 3: spontaneous bleeding, ulceration). The entire colorectum was examined, and sites with the most severe inflammation were evaluated. We studied the rate of mucosal healing on colonoscopic examination at the time of clinical remission and examined the relation between mucosal healing and remission maintenance. Results: 1) The Mayo endoscopic subscore was 0 in only 4 patients (8.5%), 1 in 23 patients (49%), 2 in 16 patients (34%), and 3 in 4 patients (8.5%). Some active lesions were found in 43 patients (91.5%) in clinical remission. The following medical treatments were being received at the time of colonoscopy in 46 patients (98%): 5-aminosalicylic acid preparations in 41 (89%), immunomodulators in 2 (4%), prednisolone in 8 (17%), and local therapy in 10 (22%). 2)The rate of remission maintenance according to the Kaplan-Meier method 6 months after colonoscopy was 100% in patients with a score of 0, 96% in those with a score of 1, 75% in those with a score 2, and 50% in those with a score of 3. The rates of remission maintenance after 60 months were 50%, 48%, 31%, and 0%, respectively. The differences among the 4 groups were significant on the log-rank (p ,0.001). Conclusions: The rate of mucosal healing on colonoscopic examination was low even in patients who had achieved clinical remission. Patients with residual ulcers or erosions had higher rates of flare-ups within a short period. Not only clinical findings, but also mucosal healing on colonoscopic examination should be evaluated in patients scheduled to receive remission maintenance therapy for UC.
Su1206 Mucosal Healing Is Associated With Improved Long-Term Outcome of Maintenance Therapy With Natalizumab in Crohn's Disease Atsushi Sakuraba, Maria Laura Annunziata, Russell D. Cohen, Stephen B. Hanauer, David T. Rubin Background: Natalizumab is an efficacious agent for induction and maintenance of remission in Crohn's disease (CD) patients. We aimed to assess the impact of endoscopic severity and mucosal healing on the long-term outcome of natalizumab treatment in CD. Methods: We retrospectively assessed endoscopic severity according to the Simple Endoscopic Score for Crohn's Disease (SESCD) in CD patients who received natalizumab therapy and compared the degree of endoscopic severity prior to natalizumab treatment with mucosal healing after treatment, and the correlations with outcome of therapy. Baseline SESCD was categorized into quartiles. Mucosal healing was defined as significant (reduction of SESCD of .70%), partial (20-60%), and none (,20%) based on the degree of improvement of SESCD from baseline to follow-up ileocolonoscopy. Outcome of therapy was defined as duration of continuing natalizumab along with a physician determined clinical response, which was compared between groups by Kaplan-Meier method. Results: Thirty-two CD patients (15 male, median age 32.5 years, median duration of disease 180 months) receiving natalizumab underwent at least one ileocolonoscopy before or during natalizumab treatment. One patient had isolated ileal disease, five had colonic disease and 26 had ileocolitis, and 50% had a history of Crohn's related surgery. All patients had previously failed immunomodulator(s) and 31 had failed anti-tumor necrosis factor agent(s). Mean duration of natalizumab treatment was 14.1 months. Those with a greater baseline SESCD were less likely to respond to treatment as assessed by Kaplan-Meier survival analysis (n = 32, log-rank test, p = 0.0055). Significant mucosal healing (reduction of SESCD of .70%) was achieved in 11 of 26 patients (42.3%), and correlated with an improved long-term outcome as shown by longer duration on therapy compared to those only achieving partial (n = 9) or no (n = 6) mucosal healing (log-rank test, p = 0.032). Conclusion: The degree of endoscopic inflammation correlates to duration of therapy with natalizumab. Endoscopic evaluation provides prognostic information in natalizumab treated CD patients and may be valuable in monitoring clinical responsiveness to therapy. Figure Legends Figure 1. (A) Kaplan-Meier survival analysis based on the baseline SESCD quartiles. Among all quartile groups, there was a significant difference in outcome of therapy (log-rank test, p = 0.0055). (B) Kaplan-Meier survival analysis based on the level of mucosal healing. Outcome of therapy among those who achieved significant (.70% reduction of SESCD), partial (20-70%) or no ( ,20%) improvement were significantly different (log-rank test, p = 0.032).
Su1208 Effectiveness of Split-Dose Certolizumab Pegol for the Treatment of Crohn's Disease: Experience At a Tertiary Care Center Sunanda V. Kane, Brenda D. Becker, Brittny Neis, David H. Bruining, William A. Faubion, Karen A. Hanson, John B. Kisiel, Edward V. Loftus, Darrell S. Pardi, Laura H. Raffals, Kenneth W. Schroeder, William J. Tremaine Background and Aims: To date there are several clinical trials evaluating the effectiveness of certolizumab pegol (CZP) for Crohn's Disease (CD). There are limited published data evaluating the efficacy of CZP in clinical practice, and even more limited data regarding the effectiveness of split-dose modification (200 mg every 2 weeks). We evaluated the efficacy of CZP split-dose modification in CD patients who experienced active symptoms despite a standard maintenance dose of CZP (400 mg once monthly). In addition, we evaluated patients who received split-dose modification as their initial dosing regimen. Methods: Retrospective chart review of CZP-treated CD patients seen in an inflammatory bowel disease clinic at a tertiary care center. Patients with documented prescriptions for CZP were pulled
S-427
AGA Abstracts
AGA Abstracts
Long-Term Outcome of Treatment With Infliximab in Patients With SteroidDependent Ulcerative Colitis Alessandro Armuzzi, Daniela Pugliese, Silvio Danese, Gianluca Rizzo, Manuela Marzo, Carla Felice, Gianluca Andrisani, Gionata Fiorino, Olga Maria Nardone, Italo De Vitis, Alfredo Papa, Gian Ludovico Rapaccini, Luisa Guidi Background & Aims: Up to 40% of ulcerative colitis (UC) patients need steroids during their course and 20% of them become steroid-dependent. Thiopurines are recommended in steroid-dependent UC, but their efficacy is debated. We recently reported more than 30% of steroid-free clinical remission and mucosal healing for UC patients after 1 year of infliximab (IFX) treatment1. Aims of our study were to describe the long-term outcome of IFX treatment in active steroid-dependent UC and to investigate if predictors of sustained clinical response and colectomy could be identified. Methods: Consecutive patients with active steroid-dependent UC treated with IFX were studied. Co-primary outcomes were 1) sustained clinical response in patients who achieved clinical remission (no diarrhoea, no blood) or response (clinical improvement, despite persistent blood loss) after induction and 2) colectomy free-survival. Sustained clinical response was defined as a persistent clinical improvement during the follow-up, without need of a new course of steroids. Results: 126 steroid-dependent UC patients were included. 45% of them were Naïve to thiopurines and 56% were started on concomitant thiopurines. The median duration of follow-up was 32 months (IQR 22-62), with a median number of infusion per patient of 14 (IQR 7-24). The colectomy rate was 23% (29/126), with a median time to colectomy of 16 months (IQR 930). After induction, 77% (97/126) of patients achieved clinical benefit. Among them, 47% (46/97) had a sustained clinical response during follow-up. 88 of 126 patients were on steroids at enrolment (daily median equivalent of prednisone dose: 25 mg, IQR 15-30) and 46% (41/88) withdrew steroids during long-term IFX treatment. Cox regression identified the Mayo endoscopic score ≥2 at baseline (p=0.03, HR 2.7, 95%CI 1.1-6.9) and high Creactive protein (CRP) after induction (p=0.001, HR 5.5, 95%CI 1.9-15) as independent predictors of colectomy. Thiopurine Naïve status (p=0.03, HR 0.35, 95%CI 0.1-0.9) was protective from colectomy. Combination therapy of IFX and thiopurines (p ,0.0001, HR 6.2, 95%CI 2.6-14) was identified as independent predictor of sustained clinical response. Serious adverse events leading to IFX withdrawal were recorded in 11.1% of patients. Conclusions: Infliximab long-term treatment is effective in this large cohort of steroiddependent UC patients. The severity of endoscopic lesions at baseline and a persistently high CRP after induction are associated with higher rates of colectomy. Conversely, thiopurine Naïve status is protective from colectomy. Combination therapy is predictive of sustained clinical response. 1) Armuzzi A, et al. Gastroenterology 2012;142(Suppl. 1):S205; Inflamm Bowel Dis 2012: in press.
Su1207 Relation Between Mucosal Healing and Long-Term Outcomes in Patients With Ulcerative Colitis Kaoru Yokoyama, Kiyonori Kobayashi, Miyuki Mukae, Miwa Sada, Wasaburo Koizumi Objectives: Mucosal healing is considered an important factor in the assessment of therapeutic effectiveness and treatment goals in inflammatory bowel disease. However, long-term studies of whether mucosal healing contributes to remission maintenance remain inadequate. We performed colonoscopy in patients with ulcerative colitis (UC) who had clinical remission to clarify the relation between endoscopic findings and outcomes. Subjects and Methods: We studied 47 patients with UC in clinical remission as confirmed by total colonoscopy between January 2005 and December 2006 who were subsequently followed up for 5 years. At the initial attack, the extent of UC was pancolitis in 13 patients (28%), left-sided colitis in 14 (30%), proctitis in 12 (26%), and unknown in 8 (17%) who were transferred from other hospitals. The Mayo score was used to assess clinical response. Clinical remission was defined as a score of 0 for both daily stool frequency and bloody stools. Flare-ups were defined as the need to use additional drugs or to alter the treatment regimen. Endoscopic findings were evaluated according to the Mayo endoscopic subscore classification (0: normal or inactive disease, 1: erythema, decreased vascular pattern, 2: marked erythema, absent vascular pattern, friability, erosions, and 3: spontaneous bleeding, ulceration). The entire colorectum was examined, and sites with the most severe inflammation were evaluated. We studied the rate of mucosal healing on colonoscopic examination at the time of clinical remission and examined the relation between mucosal healing and remission maintenance. Results: 1) The Mayo endoscopic subscore was 0 in only 4 patients (8.5%), 1 in 23 patients (49%), 2 in 16 patients (34%), and 3 in 4 patients (8.5%). Some active lesions were found in 43 patients (91.5%) in clinical remission. The following medical treatments were being received at the time of colonoscopy in 46 patients (98%): 5-aminosalicylic acid preparations in 41 (89%), immunomodulators in 2 (4%), prednisolone in 8 (17%), and local therapy in 10 (22%). 2)The rate of remission maintenance according to the Kaplan-Meier method 6 months after colonoscopy was 100% in patients with a score of 0, 96% in those with a score of 1, 75% in those with a score 2, and 50% in those with a score of 3. The rates of remission maintenance after 60 months were 50%, 48%, 31%, and 0%, respectively. The differences among the 4 groups were significant on the log-rank (p ,0.001). Conclusions: The rate of mucosal healing on colonoscopic examination was low even in patients who had achieved clinical remission. Patients with residual ulcers or erosions had higher rates of flare-ups within a short period. Not only clinical findings, but also mucosal healing on colonoscopic examination should be evaluated in patients scheduled to receive remission maintenance therapy for UC.
Su1206 Mucosal Healing Is Associated With Improved Long-Term Outcome of Maintenance Therapy With Natalizumab in Crohn's Disease Atsushi Sakuraba, Maria Laura Annunziata, Russell D. Cohen, Stephen B. Hanauer, David T. Rubin Background: Natalizumab is an efficacious agent for induction and maintenance of remission in Crohn's disease (CD) patients. We aimed to assess the impact of endoscopic severity and mucosal healing on the long-term outcome of natalizumab treatment in CD. Methods: We retrospectively assessed endoscopic severity according to the Simple Endoscopic Score for Crohn's Disease (SESCD) in CD patients who received natalizumab therapy and compared the degree of endoscopic severity prior to natalizumab treatment with mucosal healing after treatment, and the correlations with outcome of therapy. Baseline SESCD was categorized into quartiles. Mucosal healing was defined as significant (reduction of SESCD of .70%), partial (20-60%), and none (,20%) based on the degree of improvement of SESCD from baseline to follow-up ileocolonoscopy. Outcome of therapy was defined as duration of continuing natalizumab along with a physician determined clinical response, which was compared between groups by Kaplan-Meier method. Results: Thirty-two CD patients (15 male, median age 32.5 years, median duration of disease 180 months) receiving natalizumab underwent at least one ileocolonoscopy before or during natalizumab treatment. One patient had isolated ileal disease, five had colonic disease and 26 had ileocolitis, and 50% had a history of Crohn's related surgery. All patients had previously failed immunomodulator(s) and 31 had failed anti-tumor necrosis factor agent(s). Mean duration of natalizumab treatment was 14.1 months. Those with a greater baseline SESCD were less likely to respond to treatment as assessed by Kaplan-Meier survival analysis (n = 32, log-rank test, p = 0.0055). Significant mucosal healing (reduction of SESCD of .70%) was achieved in 11 of 26 patients (42.3%), and correlated with an improved long-term outcome as shown by longer duration on therapy compared to those only achieving partial (n = 9) or no (n = 6) mucosal healing (log-rank test, p = 0.032). Conclusion: The degree of endoscopic inflammation correlates to duration of therapy with natalizumab. Endoscopic evaluation provides prognostic information in natalizumab treated CD patients and may be valuable in monitoring clinical responsiveness to therapy. Figure Legends Figure 1. (A) Kaplan-Meier survival analysis based on the baseline SESCD quartiles. Among all quartile groups, there was a significant difference in outcome of therapy (log-rank test, p = 0.0055). (B) Kaplan-Meier survival analysis based on the level of mucosal healing. Outcome of therapy among those who achieved significant (.70% reduction of SESCD), partial (20-70%) or no ( ,20%) improvement were significantly different (log-rank test, p = 0.032).
Su1208 Effectiveness of Split-Dose Certolizumab Pegol for the Treatment of Crohn's Disease: Experience At a Tertiary Care Center Sunanda V. Kane, Brenda D. Becker, Brittny Neis, David H. Bruining, William A. Faubion, Karen A. Hanson, John B. Kisiel, Edward V. Loftus, Darrell S. Pardi, Laura H. Raffals, Kenneth W. Schroeder, William J. Tremaine Background and Aims: To date there are several clinical trials evaluating the effectiveness of certolizumab pegol (CZP) for Crohn's Disease (CD). There are limited published data evaluating the efficacy of CZP in clinical practice, and even more limited data regarding the effectiveness of split-dose modification (200 mg every 2 weeks). We evaluated the efficacy of CZP split-dose modification in CD patients who experienced active symptoms despite a standard maintenance dose of CZP (400 mg once monthly). In addition, we evaluated patients who received split-dose modification as their initial dosing regimen. Methods: Retrospective chart review of CZP-treated CD patients seen in an inflammatory bowel disease clinic at a tertiary care center. Patients with documented prescriptions for CZP were pulled
S-427
AGA Abstracts