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Tu1347 Response to Anti-TNF Therapy in Hispanics With Inflammatory Bowel Disease: A Prospective Cohort Study
Tu1346
Serology Panel for Prediction of Relapse After Discontinuation of Infliximab in Patients With Crohn's Disease Achieving Clinical Remission Konstantinos Papamichael, Karolien Claes, Magali de Bruyn, Fred Princen, Sharat Singh, Gert A. Van Assche, Paul J. Rutgeerts, Severine Vermeire, Marc Ferrante, Scott Hauenstein
Skin and Joint Side Effects in a Subpopulation of Anti-TNF Experienced IBD Patients, Who Respond to a Treatment With Vedolizumab, a Humanized A4b7 Integrin Antibody Oliver Drvarov, Raed AbuHashem, Natalie Schunk, Stefan Schreiber, Tanja Kuehbacher
Background and aim: Stopping rules for anti-tumor necrosis factor (TNF) therapy are urgently needed. The identification of predictive markers identifying patients at low or high risk for relapse after stopping is therefore warranted. There are limited data concerning the role of non-invasive, serological factors as predictors of relapse after anti-TNF cessation in patients with Crohn's disease (CD). Therefore, we investigated whether a novel serology panel for assessment of wound healing and repair can predict relapse after infliximab (IFX) cessation for clinical remission in patients with CD. Material and methods: This was an observational, retrospective, single-center study. From an electronic database we identified 100 CD patients (57 luminal CD, 40 male, median age at diagnosis 25 years) who discontinued IFX for clinical remission. The majority of patients (n=84) continued on immunomodulators. Relapse was defined as the need to re-introduce medical therapy or surgery. The serology panel included serum TNFα, amphiregulin (AREG), epiregulin (EREG), heparin-binding EGF-like growth factor (HBEGF), hepatocyte growth factor (HGF), heregulin beta EGF domain (HRGB), betacellulin (BTC), epidermal growth factor (EGF), and transforming growth factor alpha (TGFα). These markers were determined in samples taken at the time of IFX discontinuation by Prometheus Laboratories (San Diego, CA). A test was considered positive if the titers were higher than the Q3 of the samples measurements: [TNFα, (>12 μg/ml), AREG (>20 U/ml), EREG (>243 U/ml), HBEGF (>12 U/ml), HGF (>74 U/ml), HRGB (>33 U/ml), BTC (>235 U/ml), EGF (>88 U/ml), TGFα (>7 U/ml)]. Results: During a median (IQR) follow up of 9.7 (8.0-11.5) years, 48 out of 100 patients relapsed. A receiver operating characteristic (ROC) analysis did not identify predictive cut-off values for relapse after IFX discontinuation for any of the investigated serological markers. Univariate (Log-Rank) and multiple COX regression analysis revealed borderline significance for positive AREG in predicting relapse (p=0.066 and 0.068 respectively). However, multiple COX regression analysis for a sub-group of patients treated mainly for luminal disease, identified positive AREG as an independent factor predicting relapse after IFX cessation [n=34, p=0.008, HR: 8.1 (95%CI: 1.7-38.1), SN: 80%, SP: 52%, PPV: 22%, NPV: 94%]. Conclusion: Positive amphiregulin titers may be associated with relapse in patients who discontinue IFX for clinical remission. AREG is a member of the epidermal growth factor family which is highly expressed only in the active inflamed and not in the normal mucosa of CD patients.1 Our results warrant further study of the role of serum AREG in mucosal healing and repair in IBD. 1 Nishimura T, et al. Oncol Rep 2008.
Background: No specific side effects were reported in the phase II and III vedolizumab trials in IBD patients. Anti-TNF experienced patients are an increasing subpopulation in IBD. Response, remission and often side effects of new drugs in this patient group differ from biological naïve patients. Methods: 43 Crohn's disease (CD) and 35 ulcerative colitis (UC) patients with chronic active refractory disease (CDAI > 220, CAI>6), who did not respond or were intolerant to anti TNFantagonists were treated with vedolizumab. Response was controlled by CRP, calprotectin, sonography and sigmoidoscopy or colonoscopy at baseline, week 6 and week 14. Results: The mean age of the patients in the CD group was 38 years, in the UC group 39 years. Only patients who responded to the treatment of vedolizumab and received at least 4 infusions were included in the analysis. Mean CRP in the CD group was 20.2 mg/l at baseline and 10 mg/l at week 14. Mean CRP in the UC group was14.8 mg/l at baseline and 5.4 mg/l at week 14. Mean CDAI at baseline in the CD group was 352, CAI in the UC group 10. CDAI at week 14 was 169, CAI 4. Calprotectin was significantly decreased at week 14. After 2 infusions of vedolizumab 2 (4.7%) of the CD patients and 4 (11.4%) of the UC patients showed acne like skin lesions in the face, back and breast. 5 (11.6%) of the CD and 5 (14.3%) of the UC patients showed at the same timepoint severe arthritis and joint swelling and a newly established erythema nodosa. 11(25.6%) of the CD and 3 (8.6) of the UC patients had both acne like skin lesions and extreme arthritis with swelling of the joints of the hand and feet ankle joints. In total 17 (39.5%) of the CD and 12 (34.3%) of the UC patients showed at least either one of these side effects or both.There was no increase in inflammatory parameters or newly detected autoantibodies. The symptoms improved during further therapy and vanished at least before the 5th infusion. Conclusion: The increased arthritis symptoms and acne like lesions started after 2 Infusions of vedolizumab and vanished without therapy during ongoing treatment with vedolizumab. All of these patients had an excellent response to the vedolizumab treatment. Further investigations have to explore the immunological background of these side effects. Tu1347 Response to Anti-TNF Therapy in Hispanics With Inflammatory Bowel Disease: A Prospective Cohort Study Nirupama Bonthala, Rahel Demisse, Mona Rezapour, Caroline Hwang
Tu1345
Background: The incidence of inflammatory bowel disease (IBD) has been increasing globally, both in developing nations and immigrant groups in western nations. Despite being the fastest growing minority group in the US, there is little data about anti-TNF response in Hispanics with IBD. Methods: We enrolled IBD patients seen from 2010 to 2014 at a single center in a metropolitan area with a large Hispanic population. Patients completed a questionnaire that included ethnicity. A prospective database was collected which included disease subtype (Crohn's disease [CD] or ulcerative colitis [UC]), and medication/surgical history. The following anti-TNF response outcomes were analyzed: steroid-free clinical response by week 24, primary nonresponse (minimal symptom improvement by week 8) and secondary loss of response (initial response, but subsequent needed for steroids, therapy escalation or surgery by one year). Results: 297 patients were included, of which 62%(185) were Hispanic. Overall, Hispanic IBD patients were treated with anti-TNF therapy at a similar rate as non-Hispanics (28% vs 34%, p=0.15). 21% of Hispanics with UC and 49% with CD were on an anti-TNF. Disease extent in UC patients on anti-TNF were similar between Hispanics and non-Hispanics (85% vs 76%). For CD, Hispanics on anti-TNF were more likely than non-Hispanics to have disease limited to the colon (39% vs 15%, p=0.04) and also to less stricturing or penetrating disease (52% vs 84%, p=0.015). In regards to response to anti-TNF, Hispanics had a higher rate of primary nonresponse at 46%, compared to non-Hispanics (13%, p=0.029). Hispanic primary nonresponders were more likely than responders to have UC rather than CD (83% v 42%, p=0.01), but were similar in age, gender and disease duration. Steroid-free response rate at week 24 was 23% in Hispanic UC patients and 30% in Hispanic CD patients. These were slightly lower than that seen in non-Hispanics (33% UC vs 50% CD, p=0.08). At one year, secondary loss of response (LOR) in Hispanics was 19% in UC and 46% in CD, which were similar to non-Hispanics. In those with secondary LOR, 40% of UC patients underwent colectomy by 1 year. For CD patients, 66% were recaptured by optimizing dose or changing within class. Hispanics with secondary LOR had a higher BMI at initiation of anti-TNF at 29.3 compared to long-term responders (24.9, p=0.046) and primary nonresponders (25.03, p=0.068). Conclusions: Hispanics requiring anti-TNF appear to have important differences compared to non-Hispanics. This included disease confined to the colon (UC and CD colitis) and less stricturing/ penetrating CD. Despite these findings, Hispanics seemed to have a higher rate of primary nonresponse to anti-TNF. Secondary LOR was common and seemed to be associated with higher BMI.Further studies confirming disparities in treatment response are warranted.
Efficacy and Safety of Anti-TNF Therapy for Inflammatory Bowel Disease (IBD) in Liver Transplant Recipients for Primary Sclerosing Cholangitis (PSC): A Multicenter Experience Roman Combes, Romain Altwegg, David Laharie, Victor de Ledinghen, Sylvie Radenne, Filomena Conti, Olivier Chazouilleres, Christophe Duvoux, Laurent Peyrin-Biroulet, Jérôme Dumortier, Vincent Leroy, Xavier Treton, Francois Durand, Sébastien Dharancy, Maria Nachury, Félix Goutorbe, Géraldine Lamblin, Georges-Philippe Pageaux Background: The management of IBD after liver transplantation (LT) for PSC is complex due to the immunosuppression background and the risk of IBD worsening after LT. The aim of this study was to assess efficacy and safety of anti-TNF therapy in this population. Methods: It was a retrospective, descriptive, national multicentric study. All the French adult LT centers have been contacted to indentify and include patients who underwent LT for PSC between January 1985 and December 2012 then treated by anti-TNF therapy for IBD. Medical datas were screened to assess clinical efficacy, endoscopic efficacy and safety after induction and at the end of the treatment. Results: Eighteen patients (14 men, 4 women), who underwent LT for PSC between 1989 and 2012, followed in 9 of the 20 adult LT French centers have been treated by anti-TNF therapy between 2004 and 2014 for IBD after LT. All patients presented colonic location. The median age at the beginning of the treatment (Day 0) was 37.2 years (24.0-51.9). The median time between LT and Day 0 was 5.9 years (1.1-20.8). The median duration of IBD evolution at Day 0 was 14.1 years (0.427.6). Seven patients (38.9%) received infliximab, 7 (38.9) adalimumab and 4 (22.2%) received both successively. The median duration of treatment was 10.4 months (2.7-30.6) and the median follow-up was 20.9 months (5.0-72.5). Six patients (33%) were treated with azathioprine. Seventeen (94.4%) were treated by tacrolimus and 1 (5.6%) by ciclosporine. After induction, 16 patients (88.9%) presented a clinical improvement of which 10 (55.6%) were in clinical remission. At the date of latest news, 12 patients (66.7%) showed clinical improvement of which 7 (38.9%) were in clinical remission. An endoscopic improvement was found in 9 of the 14 patients (64.3%) with endoscopic follow-up. The treatment was continued in 10 of the 18 patients (55.6%). Six patients (33.3%) presented at least one infection during the follow-up. Three patients (16.7%) developed a colon cancer of wich 1 with fatal outcome. They suffered from an IBD with an evolution duration of respectively 14, 27 and 28 years and had been treated by an anti-TNF therapy respectively 7, 2 and 8 months before the cancer diagnosis. One patient developed a cancer of the cervix. Conclusion : The efficacy of anti-TNF therapy in patients with relapsing IBD after a LT for PSC seems to be similar to that observed in non-transplanted patients. The safety seems acceptable with an infectious risk due to the context and the immunosuppressive regimen. An endoscopic follow-up with a screening for colonic dysplasia is essential in this population.
Tu1348 Biosimilar Infliximab in Inflammatory Bowel Diseases: First Interim Results From a Prospective Nationwide Observational Cohort Krisztina Gecse, Klaudia Farkas, Barbara D. Lovasz, János Banai, Petra A. Golovics, Tunde Kristof, Laszlo Lakatos, Pal Miheller, Karoly Palatka, Maria Papp, Tamas Szamosi, Zoltan Szepes, Aron Vincze, Tamas Molnar, Peter L. Lakatos Introduction: Biosimilars are biologic medicines that enter the market subsequent to an original reference product whose patent has expired. Biosimilar infliximab received EMA approval in June 2013 and entered the Hungarian market in May 2014. Few data is yet available on the safety and efficacy of biosimilar infliximab in extrapolated indications, such as inflammatory bowel diseases (IBD). Patients and Methods: A prospective, nationwide,
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AGA Abstracts
AGA Abstracts
Tu1344
Serology Panel for Prediction of Relapse After Discontinuation of Infliximab in Patients With Crohn's Disease Achieving Clinical Remission Konstantinos Papamichael, Karolien Claes, Magali de Bruyn, Fred Princen, Sharat Singh, Gert A. Van Assche, Paul J. Rutgeerts, Severine Vermeire, Marc Ferrante, Scott Hauenstein
Skin and Joint Side Effects in a Subpopulation of Anti-TNF Experienced IBD Patients, Who Respond to a Treatment With Vedolizumab, a Humanized A4b7 Integrin Antibody Oliver Drvarov, Raed AbuHashem, Natalie Schunk, Stefan Schreiber, Tanja Kuehbacher
Background and aim: Stopping rules for anti-tumor necrosis factor (TNF) therapy are urgently needed. The identification of predictive markers identifying patients at low or high risk for relapse after stopping is therefore warranted. There are limited data concerning the role of non-invasive, serological factors as predictors of relapse after anti-TNF cessation in patients with Crohn's disease (CD). Therefore, we investigated whether a novel serology panel for assessment of wound healing and repair can predict relapse after infliximab (IFX) cessation for clinical remission in patients with CD. Material and methods: This was an observational, retrospective, single-center study. From an electronic database we identified 100 CD patients (57 luminal CD, 40 male, median age at diagnosis 25 years) who discontinued IFX for clinical remission. The majority of patients (n=84) continued on immunomodulators. Relapse was defined as the need to re-introduce medical therapy or surgery. The serology panel included serum TNFα, amphiregulin (AREG), epiregulin (EREG), heparin-binding EGF-like growth factor (HBEGF), hepatocyte growth factor (HGF), heregulin beta EGF domain (HRGB), betacellulin (BTC), epidermal growth factor (EGF), and transforming growth factor alpha (TGFα). These markers were determined in samples taken at the time of IFX discontinuation by Prometheus Laboratories (San Diego, CA). A test was considered positive if the titers were higher than the Q3 of the samples measurements: [TNFα, (>12 μg/ml), AREG (>20 U/ml), EREG (>243 U/ml), HBEGF (>12 U/ml), HGF (>74 U/ml), HRGB (>33 U/ml), BTC (>235 U/ml), EGF (>88 U/ml), TGFα (>7 U/ml)]. Results: During a median (IQR) follow up of 9.7 (8.0-11.5) years, 48 out of 100 patients relapsed. A receiver operating characteristic (ROC) analysis did not identify predictive cut-off values for relapse after IFX discontinuation for any of the investigated serological markers. Univariate (Log-Rank) and multiple COX regression analysis revealed borderline significance for positive AREG in predicting relapse (p=0.066 and 0.068 respectively). However, multiple COX regression analysis for a sub-group of patients treated mainly for luminal disease, identified positive AREG as an independent factor predicting relapse after IFX cessation [n=34, p=0.008, HR: 8.1 (95%CI: 1.7-38.1), SN: 80%, SP: 52%, PPV: 22%, NPV: 94%]. Conclusion: Positive amphiregulin titers may be associated with relapse in patients who discontinue IFX for clinical remission. AREG is a member of the epidermal growth factor family which is highly expressed only in the active inflamed and not in the normal mucosa of CD patients.1 Our results warrant further study of the role of serum AREG in mucosal healing and repair in IBD. 1 Nishimura T, et al. Oncol Rep 2008.
Background: No specific side effects were reported in the phase II and III vedolizumab trials in IBD patients. Anti-TNF experienced patients are an increasing subpopulation in IBD. Response, remission and often side effects of new drugs in this patient group differ from biological naïve patients. Methods: 43 Crohn's disease (CD) and 35 ulcerative colitis (UC) patients with chronic active refractory disease (CDAI > 220, CAI>6), who did not respond or were intolerant to anti TNFantagonists were treated with vedolizumab. Response was controlled by CRP, calprotectin, sonography and sigmoidoscopy or colonoscopy at baseline, week 6 and week 14. Results: The mean age of the patients in the CD group was 38 years, in the UC group 39 years. Only patients who responded to the treatment of vedolizumab and received at least 4 infusions were included in the analysis. Mean CRP in the CD group was 20.2 mg/l at baseline and 10 mg/l at week 14. Mean CRP in the UC group was14.8 mg/l at baseline and 5.4 mg/l at week 14. Mean CDAI at baseline in the CD group was 352, CAI in the UC group 10. CDAI at week 14 was 169, CAI 4. Calprotectin was significantly decreased at week 14. After 2 infusions of vedolizumab 2 (4.7%) of the CD patients and 4 (11.4%) of the UC patients showed acne like skin lesions in the face, back and breast. 5 (11.6%) of the CD and 5 (14.3%) of the UC patients showed at the same timepoint severe arthritis and joint swelling and a newly established erythema nodosa. 11(25.6%) of the CD and 3 (8.6) of the UC patients had both acne like skin lesions and extreme arthritis with swelling of the joints of the hand and feet ankle joints. In total 17 (39.5%) of the CD and 12 (34.3%) of the UC patients showed at least either one of these side effects or both.There was no increase in inflammatory parameters or newly detected autoantibodies. The symptoms improved during further therapy and vanished at least before the 5th infusion. Conclusion: The increased arthritis symptoms and acne like lesions started after 2 Infusions of vedolizumab and vanished without therapy during ongoing treatment with vedolizumab. All of these patients had an excellent response to the vedolizumab treatment. Further investigations have to explore the immunological background of these side effects. Tu1347 Response to Anti-TNF Therapy in Hispanics With Inflammatory Bowel Disease: A Prospective Cohort Study Nirupama Bonthala, Rahel Demisse, Mona Rezapour, Caroline Hwang
Tu1345
Background: The incidence of inflammatory bowel disease (IBD) has been increasing globally, both in developing nations and immigrant groups in western nations. Despite being the fastest growing minority group in the US, there is little data about anti-TNF response in Hispanics with IBD. Methods: We enrolled IBD patients seen from 2010 to 2014 at a single center in a metropolitan area with a large Hispanic population. Patients completed a questionnaire that included ethnicity. A prospective database was collected which included disease subtype (Crohn's disease [CD] or ulcerative colitis [UC]), and medication/surgical history. The following anti-TNF response outcomes were analyzed: steroid-free clinical response by week 24, primary nonresponse (minimal symptom improvement by week 8) and secondary loss of response (initial response, but subsequent needed for steroids, therapy escalation or surgery by one year). Results: 297 patients were included, of which 62%(185) were Hispanic. Overall, Hispanic IBD patients were treated with anti-TNF therapy at a similar rate as non-Hispanics (28% vs 34%, p=0.15). 21% of Hispanics with UC and 49% with CD were on an anti-TNF. Disease extent in UC patients on anti-TNF were similar between Hispanics and non-Hispanics (85% vs 76%). For CD, Hispanics on anti-TNF were more likely than non-Hispanics to have disease limited to the colon (39% vs 15%, p=0.04) and also to less stricturing or penetrating disease (52% vs 84%, p=0.015). In regards to response to anti-TNF, Hispanics had a higher rate of primary nonresponse at 46%, compared to non-Hispanics (13%, p=0.029). Hispanic primary nonresponders were more likely than responders to have UC rather than CD (83% v 42%, p=0.01), but were similar in age, gender and disease duration. Steroid-free response rate at week 24 was 23% in Hispanic UC patients and 30% in Hispanic CD patients. These were slightly lower than that seen in non-Hispanics (33% UC vs 50% CD, p=0.08). At one year, secondary loss of response (LOR) in Hispanics was 19% in UC and 46% in CD, which were similar to non-Hispanics. In those with secondary LOR, 40% of UC patients underwent colectomy by 1 year. For CD patients, 66% were recaptured by optimizing dose or changing within class. Hispanics with secondary LOR had a higher BMI at initiation of anti-TNF at 29.3 compared to long-term responders (24.9, p=0.046) and primary nonresponders (25.03, p=0.068). Conclusions: Hispanics requiring anti-TNF appear to have important differences compared to non-Hispanics. This included disease confined to the colon (UC and CD colitis) and less stricturing/ penetrating CD. Despite these findings, Hispanics seemed to have a higher rate of primary nonresponse to anti-TNF. Secondary LOR was common and seemed to be associated with higher BMI.Further studies confirming disparities in treatment response are warranted.
Efficacy and Safety of Anti-TNF Therapy for Inflammatory Bowel Disease (IBD) in Liver Transplant Recipients for Primary Sclerosing Cholangitis (PSC): A Multicenter Experience Roman Combes, Romain Altwegg, David Laharie, Victor de Ledinghen, Sylvie Radenne, Filomena Conti, Olivier Chazouilleres, Christophe Duvoux, Laurent Peyrin-Biroulet, Jérôme Dumortier, Vincent Leroy, Xavier Treton, Francois Durand, Sébastien Dharancy, Maria Nachury, Félix Goutorbe, Géraldine Lamblin, Georges-Philippe Pageaux Background: The management of IBD after liver transplantation (LT) for PSC is complex due to the immunosuppression background and the risk of IBD worsening after LT. The aim of this study was to assess efficacy and safety of anti-TNF therapy in this population. Methods: It was a retrospective, descriptive, national multicentric study. All the French adult LT centers have been contacted to indentify and include patients who underwent LT for PSC between January 1985 and December 2012 then treated by anti-TNF therapy for IBD. Medical datas were screened to assess clinical efficacy, endoscopic efficacy and safety after induction and at the end of the treatment. Results: Eighteen patients (14 men, 4 women), who underwent LT for PSC between 1989 and 2012, followed in 9 of the 20 adult LT French centers have been treated by anti-TNF therapy between 2004 and 2014 for IBD after LT. All patients presented colonic location. The median age at the beginning of the treatment (Day 0) was 37.2 years (24.0-51.9). The median time between LT and Day 0 was 5.9 years (1.1-20.8). The median duration of IBD evolution at Day 0 was 14.1 years (0.427.6). Seven patients (38.9%) received infliximab, 7 (38.9) adalimumab and 4 (22.2%) received both successively. The median duration of treatment was 10.4 months (2.7-30.6) and the median follow-up was 20.9 months (5.0-72.5). Six patients (33%) were treated with azathioprine. Seventeen (94.4%) were treated by tacrolimus and 1 (5.6%) by ciclosporine. After induction, 16 patients (88.9%) presented a clinical improvement of which 10 (55.6%) were in clinical remission. At the date of latest news, 12 patients (66.7%) showed clinical improvement of which 7 (38.9%) were in clinical remission. An endoscopic improvement was found in 9 of the 14 patients (64.3%) with endoscopic follow-up. The treatment was continued in 10 of the 18 patients (55.6%). Six patients (33.3%) presented at least one infection during the follow-up. Three patients (16.7%) developed a colon cancer of wich 1 with fatal outcome. They suffered from an IBD with an evolution duration of respectively 14, 27 and 28 years and had been treated by an anti-TNF therapy respectively 7, 2 and 8 months before the cancer diagnosis. One patient developed a cancer of the cervix. Conclusion : The efficacy of anti-TNF therapy in patients with relapsing IBD after a LT for PSC seems to be similar to that observed in non-transplanted patients. The safety seems acceptable with an infectious risk due to the context and the immunosuppressive regimen. An endoscopic follow-up with a screening for colonic dysplasia is essential in this population.
Tu1348 Biosimilar Infliximab in Inflammatory Bowel Diseases: First Interim Results From a Prospective Nationwide Observational Cohort Krisztina Gecse, Klaudia Farkas, Barbara D. Lovasz, János Banai, Petra A. Golovics, Tunde Kristof, Laszlo Lakatos, Pal Miheller, Karoly Palatka, Maria Papp, Tamas Szamosi, Zoltan Szepes, Aron Vincze, Tamas Molnar, Peter L. Lakatos Introduction: Biosimilars are biologic medicines that enter the market subsequent to an original reference product whose patent has expired. Biosimilar infliximab received EMA approval in June 2013 and entered the Hungarian market in May 2014. Few data is yet available on the safety and efficacy of biosimilar infliximab in extrapolated indications, such as inflammatory bowel diseases (IBD). Patients and Methods: A prospective, nationwide,
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AGA Abstracts
AGA Abstracts
Tu1344