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Tu1151 Re-Introduction of Infliximab After Consecutive Failure of Infliximab and Adalimumab Is Beneficial in Refractory Crohn's Disease
AGA Abstracts
Tu1151
Tu1153
Re-Introduction of Infliximab After Consecutive Failure of Infliximab and Adalimumab Is Beneficial in Refractory Crohn's Disease Johannan F. Brandse, Charlotte P. Peters, Emma J. Eshuis, M. Lowenberg, Cyriel Ponsioen, Gijs R. van den Brink, Geert R. D'Haens
Predictive Factors for Mucosal Healing in Crohn's Disease Patients With Unelevated Serum CRP Levels Asuka Nakarai, Sakiko Hiraoka, Jun Kato, Toshihiro Inokuchi, Mitsuhiro Akita, Tomoko Hirakawa, Keisuke Hori, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto
BACKGROUND In the last decade, Infliximab (IFX) and Adalimumab (ADA) have dramatically improved the management of steroid refractory Crohn's disease (CD). In clinical practice a considerable group of patients are switched from one agent to the other because of failure, intolerance and patient preference. There are no data regarding the long term clinical response of re-exposure to IFX in patients who sequentially used and discontinued IFX and ADA. Therefore we retrospectively assessed clinical response to IFX in CD patients that failed subsequently IFX and ADA and were re-exposed to IFX. METHODS For this survey we used a multicenter North-Holland cohort of 438 CD patients treated with ADA. Twentynine of these had previously been treated with IFX and received a second IFX treatment after failing ADA. Short-term and prolonged response to IFX was assessed retrospectively by reviewing clinical records. RESULTS 29 patients (62% luminal CD, 7% fistulizing CD, 31% both) from 8 hospitals were included with complete follow-up data up to 18 months. IFX was re-started at 5mg/kg in 20/39 (69%), 7.5 mg/kg in 1 patient and at 10 mg/kg in 8/29 (28%), at intervals varying between 4 and 8 weeks. Dose escalation was done in 8/29 (28%) of patients during retreatment with IFX. Twenty patients (69%) were on concomitant immune modulators at the re-introduction of IFX and 3 (10%) patients experienced adverse events: acute infusion reaction (n=2, 7%) and delayed hypersensitivity reaction (n=1, 3%). Clinical response is shown in figure 1: 20/29 (69%) patients were still on continued Infliximab therapy after 18 months. Reasons for discontinuing the second Infliximab therapy included: non-response (n=2, 7%), loss of response (n=3, 10%), intolerance (n=3, 10%) or noncompliance (n=1, 3%). CONCLUSION The majority of CD patients, failing prior treatment with IFX and ADA, benefit from re-introduction of Infliximab for at least 18 months. Only a small proportion of 9 patients failed on retreatment with IFX. Retreatment with Infliximab is to be considered a valuable strategy in this group of refractory CD patients.
Background & aims: Accumulating evidence has underlined the importance of mucosal healing (MH) as a treatment goal of Crohn's disease (CD). Evaluation of MH in CD is rather difficult because CD can involve entire gastrointestinal system, particularly the small bowel. In general, endoscopy including colonoscopy, capsule endoscopy, and balloon enteroscopy, and/or radiologic modalities including computed tomography, magnetic resonance imaging and fluoroscopy are necessary. In addition, repeated examinations with such modalities are required during a long-term disease course. Therefore, predictive factors for MH in place of imaging techniques are desirable. Serum C-reactive protein (CRP) levels are one of the candidates for this purpose. However, it has previously been reported that CRP levels do not elevate in 20-30% of active CD patients despite presence of disease activity. The aim of this study is to determine predictive factors for MH in CD patients without elevation of serum CRP levels. Methods: A total of 128 CD patients of whom mucosal status was evaluated by performing endoscopic and/or radiologic modalities were included in this study. Patients were divided into two groups according to serum CRP levels: CRP , 10 mg/L and . 10 mg/L. The correlation between presence of MH and values of clinical variables including CDAI, leukocyte count, platelet count, hemoglobin, serum albumin, CRP, and total cholesterol were examined in the low CRP ( , 10 mg/L) group, and predictive factors for MH in those patients were explored. Results: Of 128 patients, 33 were included in the high ( . 10 mg/L) CRP group, whereas 95 were in the low CRP group. All but one in the high CRP patients showed mucosal active inflammation, while in contrast, 41 (43%) of 95 low CRP patients manifested MH (p , 0.0001, chi-square test). In the low CRP patients, presence of MH was correlated with CDAI, hemoglobin, platelet count (PLT), and serum CRP and albumin. Multivariate analysis revealed that CDAI , 115 and PLT , 330000/μl were significant predictive factors for MH in the low CRP patients (CDAI , 115, OR = 4.66;95% CI, 1.36-17.83, p = 0.014,PLT , 330000 /μl, OR = 5.04;95% CI, 1.62-17.99, p = 0.0047). Fulfillment of these two criteria predicted MH with 0.78 (95% CI, 0.67-0.86) sensitivity, 0.74 (95% CI, 0.66-0.80) specificity, and 0.76 (95% CI, 0.66-0.83) accuracy in the low CRP patients. Conclusion: MH could be predicted noninvasively by using CDAI and platelet count in CD patients with unelevated serum CRP levels. Tu1154 Mucosal Healing Without Endoscopic Activity Predicts Long-Term Clinical Remission in Patients With Ulcerative Colitis Nagamu Inoue, Kaoru Takabayashi, Tetsuro Takayama, Katsuyoshi Matsuoka, Makoto Naganuma, Tadakazu Hisamatsu, Yuichiro Hayashi, Takanori Kanai, Haruhiko Ogata, Yasushi Iwao, Toshifumi Hibi INTRODUCTION: Mucosal healing (MH) has emerged as not only an endpoint in clinical trials but also a desirable treatment goal in clinical practice in patients with ulcerative colitis (UC). However, the role of MH on long-term disease outcomes has been evaluated in very few studies and whether MH includes endoscopic mild activity, which corresponds to Mayo endoscopic score 1, remained obscure. Therefore, in the present study, we explored the association of endoscopic activity of patients in clinical remission with their long-term clinical outcome. METHODS: We conducted a retrospective cohort study in clinical practice at a single center. Among 724 UC patients who underwent colonoscopy between in November 2007 and December 2008 at our hospital, 331 patients in corticosteroid-free clinical remission were enrolled. Demographics, clinical data, endoscopic activity, histological activity and clinical outcome after colonoscopy for at least 2 years were collected from medical records. Clinical relapse was defined as increase in bowel movement plus reappearance of rectal bleeding at 2 consecutive visits. Endoscopic activity was graded according to Mayo endoscopic score by findings of white light images. Association between variables and clinical relapse was evaluated by univariate and multivariate analyses using Cox regression model. Cumulative non-relapse rate was calculated using Kaplan-Meier survival analysis and compared among groups using log-rank test. RESULTS: The median follow-up was 39 (range 24-49) months. Overall, 69 (20.8%) patients relapsed, after a median latency of 16 (range 0-43) months. The cumulative relapse rate was 8.3, 15.5, 20.5 and 22.3% at 1, 2, 3 and 4 years. Mayo endoscopic score 1 (hazard ratio (HR): 2.86) and score 2 (HR: 3.60) was significant risk factor for clinical relapse against endoscopic score 0 (Table). Univariate analysis also identified significant association with relapse for moderate clinical activity of last flare, remission induction with cytapheresis (CAP), maintenance with imuunomodulator, shorter duration of remission and higher histological activity. Cox regression analysis after adjustment of possible confounding factors revealed that endoscopic activity, histological activity, duration of remission and remission induction with CAP were found to be independent determinants of relapse. For endoscopic activity, HR of score 1 was 2.08 to score 0 (p=0.017) but HR of score 2 was 1.01 to score 1 (not significant) (Table). Finally, the Kaplan-Meier estimate of non-relapse rate by endoscopic activity groups demonstrated significant difference (p,0.001). While there was significance between score 0 and 1, there were no significance between score 1 and 2 (Figure). CONCLUSION: The present study demonstrated that endoscopic remission (Mayo endoscopic score 0 other than score 1) predicted long-term clinical remission in UC. Risk of relapse analyzed by the Cox proportional hazard model
Figure 1 Tu1152 Parietal Healing in Patients With Crohn's Disease on Maintenance Treatment With Biologics Fabiana Castiglione, Anna Testa, Matilde Rea, Giovanni D. De Palma, Maria Diaferia, Dario Musto, Francesca Sasso, Nicola Caporaso, Antonio Rispo Introduction: Crohn's disease (CD) is usually treated by thiopurines and anti-TNF alpha agents in presence of steroid-dependency and prognostic factors of disabling disease such as perianal fistulising complications and extra-intestinal manifestations. Mucosal healing (MH) is a crucial end-point in CD patients, being a predictor of a lower need for steroids, hospitalizations and surgery in the following years. Conversely, data about parietal healing (PH) after therapy with traditional immunosuppressors and anti-TNF alpha agents are still lacking. Aim of this study was to explore the rate of PH in CD patients treated with biologics and immunosuppressors and its correlation with clinical remission (CR) and MH. Methods: In the period comprised between April 2008 and June 2012 we performed an observational longitudinal study evaluating PH, CR and MH in all CD patients on maintenance treatment with biologics or thiopurines for at least 2 years. Steroid-free CR was defined in accordance with ECCO guidelines. MH was assessed by using SES-CD while PH was recorded by using bowel sonography (BS). All patients performed endoscopy and bowel sonography before starting therapy and 2 years later. Results: The study included 66 CD patients treated by biologics and 67 patients receiving thiopurines. After 2 years of therapy, PH were evident in 17 patients on biologics and only 3 subjects treated by thiopurines (25% vs 4%; p,0.01;O.R.=6.2). CR was achieved in 37 patients (59.7 %) on biologics and in 34 patients on thiopurines (59.7% vs 53%; p=n.s.) while MH was more frequent in patients treated by anti-TNF alpha agents even if not reaching statistical significance (38% vs 25%; p=n.s.). The mean SES-CD score and the bowel wall thickness (BWT) at BS decreased significantly only in patients treated by biologics (SES-CD 11.1 vs 8.9 +2.7; p=0.001; BWT at BS 6.0 vs 4.0 +0.9; p, 0.01). Conclusions: Parietal healing can be achieved in about 25% of patients with Crohn's disease treated with anti-TNF alpha agents. Further studies are needed to define the potential role of parietal healing as long-term prognostic factor.
AGA Abstracts
S-776
Tu1151
Tu1153
Re-Introduction of Infliximab After Consecutive Failure of Infliximab and Adalimumab Is Beneficial in Refractory Crohn's Disease Johannan F. Brandse, Charlotte P. Peters, Emma J. Eshuis, M. Lowenberg, Cyriel Ponsioen, Gijs R. van den Brink, Geert R. D'Haens
Predictive Factors for Mucosal Healing in Crohn's Disease Patients With Unelevated Serum CRP Levels Asuka Nakarai, Sakiko Hiraoka, Jun Kato, Toshihiro Inokuchi, Mitsuhiro Akita, Tomoko Hirakawa, Keisuke Hori, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto
BACKGROUND In the last decade, Infliximab (IFX) and Adalimumab (ADA) have dramatically improved the management of steroid refractory Crohn's disease (CD). In clinical practice a considerable group of patients are switched from one agent to the other because of failure, intolerance and patient preference. There are no data regarding the long term clinical response of re-exposure to IFX in patients who sequentially used and discontinued IFX and ADA. Therefore we retrospectively assessed clinical response to IFX in CD patients that failed subsequently IFX and ADA and were re-exposed to IFX. METHODS For this survey we used a multicenter North-Holland cohort of 438 CD patients treated with ADA. Twentynine of these had previously been treated with IFX and received a second IFX treatment after failing ADA. Short-term and prolonged response to IFX was assessed retrospectively by reviewing clinical records. RESULTS 29 patients (62% luminal CD, 7% fistulizing CD, 31% both) from 8 hospitals were included with complete follow-up data up to 18 months. IFX was re-started at 5mg/kg in 20/39 (69%), 7.5 mg/kg in 1 patient and at 10 mg/kg in 8/29 (28%), at intervals varying between 4 and 8 weeks. Dose escalation was done in 8/29 (28%) of patients during retreatment with IFX. Twenty patients (69%) were on concomitant immune modulators at the re-introduction of IFX and 3 (10%) patients experienced adverse events: acute infusion reaction (n=2, 7%) and delayed hypersensitivity reaction (n=1, 3%). Clinical response is shown in figure 1: 20/29 (69%) patients were still on continued Infliximab therapy after 18 months. Reasons for discontinuing the second Infliximab therapy included: non-response (n=2, 7%), loss of response (n=3, 10%), intolerance (n=3, 10%) or noncompliance (n=1, 3%). CONCLUSION The majority of CD patients, failing prior treatment with IFX and ADA, benefit from re-introduction of Infliximab for at least 18 months. Only a small proportion of 9 patients failed on retreatment with IFX. Retreatment with Infliximab is to be considered a valuable strategy in this group of refractory CD patients.
Background & aims: Accumulating evidence has underlined the importance of mucosal healing (MH) as a treatment goal of Crohn's disease (CD). Evaluation of MH in CD is rather difficult because CD can involve entire gastrointestinal system, particularly the small bowel. In general, endoscopy including colonoscopy, capsule endoscopy, and balloon enteroscopy, and/or radiologic modalities including computed tomography, magnetic resonance imaging and fluoroscopy are necessary. In addition, repeated examinations with such modalities are required during a long-term disease course. Therefore, predictive factors for MH in place of imaging techniques are desirable. Serum C-reactive protein (CRP) levels are one of the candidates for this purpose. However, it has previously been reported that CRP levels do not elevate in 20-30% of active CD patients despite presence of disease activity. The aim of this study is to determine predictive factors for MH in CD patients without elevation of serum CRP levels. Methods: A total of 128 CD patients of whom mucosal status was evaluated by performing endoscopic and/or radiologic modalities were included in this study. Patients were divided into two groups according to serum CRP levels: CRP , 10 mg/L and . 10 mg/L. The correlation between presence of MH and values of clinical variables including CDAI, leukocyte count, platelet count, hemoglobin, serum albumin, CRP, and total cholesterol were examined in the low CRP ( , 10 mg/L) group, and predictive factors for MH in those patients were explored. Results: Of 128 patients, 33 were included in the high ( . 10 mg/L) CRP group, whereas 95 were in the low CRP group. All but one in the high CRP patients showed mucosal active inflammation, while in contrast, 41 (43%) of 95 low CRP patients manifested MH (p , 0.0001, chi-square test). In the low CRP patients, presence of MH was correlated with CDAI, hemoglobin, platelet count (PLT), and serum CRP and albumin. Multivariate analysis revealed that CDAI , 115 and PLT , 330000/μl were significant predictive factors for MH in the low CRP patients (CDAI , 115, OR = 4.66;95% CI, 1.36-17.83, p = 0.014,PLT , 330000 /μl, OR = 5.04;95% CI, 1.62-17.99, p = 0.0047). Fulfillment of these two criteria predicted MH with 0.78 (95% CI, 0.67-0.86) sensitivity, 0.74 (95% CI, 0.66-0.80) specificity, and 0.76 (95% CI, 0.66-0.83) accuracy in the low CRP patients. Conclusion: MH could be predicted noninvasively by using CDAI and platelet count in CD patients with unelevated serum CRP levels. Tu1154 Mucosal Healing Without Endoscopic Activity Predicts Long-Term Clinical Remission in Patients With Ulcerative Colitis Nagamu Inoue, Kaoru Takabayashi, Tetsuro Takayama, Katsuyoshi Matsuoka, Makoto Naganuma, Tadakazu Hisamatsu, Yuichiro Hayashi, Takanori Kanai, Haruhiko Ogata, Yasushi Iwao, Toshifumi Hibi INTRODUCTION: Mucosal healing (MH) has emerged as not only an endpoint in clinical trials but also a desirable treatment goal in clinical practice in patients with ulcerative colitis (UC). However, the role of MH on long-term disease outcomes has been evaluated in very few studies and whether MH includes endoscopic mild activity, which corresponds to Mayo endoscopic score 1, remained obscure. Therefore, in the present study, we explored the association of endoscopic activity of patients in clinical remission with their long-term clinical outcome. METHODS: We conducted a retrospective cohort study in clinical practice at a single center. Among 724 UC patients who underwent colonoscopy between in November 2007 and December 2008 at our hospital, 331 patients in corticosteroid-free clinical remission were enrolled. Demographics, clinical data, endoscopic activity, histological activity and clinical outcome after colonoscopy for at least 2 years were collected from medical records. Clinical relapse was defined as increase in bowel movement plus reappearance of rectal bleeding at 2 consecutive visits. Endoscopic activity was graded according to Mayo endoscopic score by findings of white light images. Association between variables and clinical relapse was evaluated by univariate and multivariate analyses using Cox regression model. Cumulative non-relapse rate was calculated using Kaplan-Meier survival analysis and compared among groups using log-rank test. RESULTS: The median follow-up was 39 (range 24-49) months. Overall, 69 (20.8%) patients relapsed, after a median latency of 16 (range 0-43) months. The cumulative relapse rate was 8.3, 15.5, 20.5 and 22.3% at 1, 2, 3 and 4 years. Mayo endoscopic score 1 (hazard ratio (HR): 2.86) and score 2 (HR: 3.60) was significant risk factor for clinical relapse against endoscopic score 0 (Table). Univariate analysis also identified significant association with relapse for moderate clinical activity of last flare, remission induction with cytapheresis (CAP), maintenance with imuunomodulator, shorter duration of remission and higher histological activity. Cox regression analysis after adjustment of possible confounding factors revealed that endoscopic activity, histological activity, duration of remission and remission induction with CAP were found to be independent determinants of relapse. For endoscopic activity, HR of score 1 was 2.08 to score 0 (p=0.017) but HR of score 2 was 1.01 to score 1 (not significant) (Table). Finally, the Kaplan-Meier estimate of non-relapse rate by endoscopic activity groups demonstrated significant difference (p,0.001). While there was significance between score 0 and 1, there were no significance between score 1 and 2 (Figure). CONCLUSION: The present study demonstrated that endoscopic remission (Mayo endoscopic score 0 other than score 1) predicted long-term clinical remission in UC. Risk of relapse analyzed by the Cox proportional hazard model
Figure 1 Tu1152 Parietal Healing in Patients With Crohn's Disease on Maintenance Treatment With Biologics Fabiana Castiglione, Anna Testa, Matilde Rea, Giovanni D. De Palma, Maria Diaferia, Dario Musto, Francesca Sasso, Nicola Caporaso, Antonio Rispo Introduction: Crohn's disease (CD) is usually treated by thiopurines and anti-TNF alpha agents in presence of steroid-dependency and prognostic factors of disabling disease such as perianal fistulising complications and extra-intestinal manifestations. Mucosal healing (MH) is a crucial end-point in CD patients, being a predictor of a lower need for steroids, hospitalizations and surgery in the following years. Conversely, data about parietal healing (PH) after therapy with traditional immunosuppressors and anti-TNF alpha agents are still lacking. Aim of this study was to explore the rate of PH in CD patients treated with biologics and immunosuppressors and its correlation with clinical remission (CR) and MH. Methods: In the period comprised between April 2008 and June 2012 we performed an observational longitudinal study evaluating PH, CR and MH in all CD patients on maintenance treatment with biologics or thiopurines for at least 2 years. Steroid-free CR was defined in accordance with ECCO guidelines. MH was assessed by using SES-CD while PH was recorded by using bowel sonography (BS). All patients performed endoscopy and bowel sonography before starting therapy and 2 years later. Results: The study included 66 CD patients treated by biologics and 67 patients receiving thiopurines. After 2 years of therapy, PH were evident in 17 patients on biologics and only 3 subjects treated by thiopurines (25% vs 4%; p,0.01;O.R.=6.2). CR was achieved in 37 patients (59.7 %) on biologics and in 34 patients on thiopurines (59.7% vs 53%; p=n.s.) while MH was more frequent in patients treated by anti-TNF alpha agents even if not reaching statistical significance (38% vs 25%; p=n.s.). The mean SES-CD score and the bowel wall thickness (BWT) at BS decreased significantly only in patients treated by biologics (SES-CD 11.1 vs 8.9 +2.7; p=0.001; BWT at BS 6.0 vs 4.0 +0.9; p, 0.01). Conclusions: Parietal healing can be achieved in about 25% of patients with Crohn's disease treated with anti-TNF alpha agents. Further studies are needed to define the potential role of parietal healing as long-term prognostic factor.
AGA Abstracts
S-776