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Biosimilar Infliximab in Anti-TNF Naive IBD Patients and One-Year Clinical Follow-Up
Sa1933
AGA Abstracts
COMBINATION THERAPY OF VEDOLIZUMAB AND A TNF ANTAGONIST IN IBD PATIENTS WITH SEVERE CHRONIC ACTIVE, THERAPY REFRACTORY DISEASE COURSE Tanja Kuehbacher, Raed AbuHashem, Natalie Langel, Stefan Schreiber, Oliver Drvarov Background: Vedolizumab and TNF antagonists are biologicals with different modes of action.Vedolizumab a humanized monoclonal antibody that specifically binds to the a4b7 integrin, blocks the interaction of the a4b7 integrin with MAdCAM-1 and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue. TNF antagonists neutralize the proinflammatory cytokine TNF, but the mode of action still remains unclear. Induction of mucosal T-cell apoptosis and downregulation of proinflammatory cytokines are only some of the identified mechanisms. 50% of IBD patients have a chronic active course of disease. Some of them suffer from a severe, so far therapy refractory disease course. A combination therapy of different biologicals might be effective in these patients. Methods: 7 patients with IBD (4 with Crohns Disease and 3 with ulcerative colitis) were treated with vedolizumab in combination with a TNF antagonist as an individual healing attempt through a case by case decision. Patients were seen as standard clinical care at baseline, week 2, 6, 14 and week 30. CDAI, CRP and calprotectin were assessed at all visits. Sonography and ileocolonoscopy or sigmoidoscopy (in ulcerative colitis patients) was performed at baseline, week 14 and week 30. SES-CDEIS and complete Mayo score was assed also at baseline, week 14 and week 30. Results: Mean CDAI at baseline: 410 (CD), Mayo score 11 (UC), CRP 39.76 mg/l (both UC and CD), fecal calprotectin 2100 mg/kg (UC), 883(CD), SES-CDEIS 31 (CD). CRP at week 2: and 6: 35.74 mg/l and 21.21 mg/l (both UC and CD), calprotectin at week 2 and 6: 1956 mg/kg (UC), 798 (CD), 1287 mg/kg (UC), 580 (CD). Mean CDAI at week 2 and 6: 404 and 383 (CD). Mean CDAI at week 14: 262 (CD), Mayo score 8 (UC), CRP 15.71 mg/l (both UC and CD), fecal calprotectin 760 mg/kg (UC), 465(CD), SES-CDEIS 22 (CD). Mean CDAI at week 30: 172 (CD), Mayo score 4 (UC), CRP 3.46 mg/l (both UC and CD), fecal calprotectin 377 mg/kg (UC), 215(CD), SES-CDEIS 11 (CD). Even so none of the patients were in complete deep remission, a significantly improvement could be seen in disease symptoms like abdominal pain and stool frequency and a significant improvement in the mucosal inflammation could be assessed by endoscopy. Conclusions: Combination therapy was well tolerated and effective. No severe infections or other severe adverse events could be seen so far. Further and larger clinical trials have to be performed in the future to investigate the efficacy and safety of anti-integrin antibodies and TNF antagonists as a combination therapy for a fast remission induction or as a maintenance combination therapy.
Table 1. Baseline characteristics.
Sa1935 BIOSIMILAR INFLIXIMAB IN ANTI-TNF NAIVE IBD PATIENTS AND ONEYEAR CLINICAL FOLLOW-UP Martin Kolar, Dana Duricova, Martin Bortlik, Veronika Hruba, Nadezda Machkova, Katarina Mitrova, Martin Lukas, Karin Malickova, Milan Lukas Background: First biosimilar infliximab (IFX) has been approved in European Union for treatment of inflammatory bowel disease (IBD) since September 2013. The approval process included extrapolation of clinical data from other indications, namely rheumatoid arthritis and ankylosing spondylitis. Data from clinical practice are therefore desirable to confirm efficacy and safety of biosimilar IFX in IBD population. Despite growing data on early treatment results, the evidence on long-term efficiency and safety of maintenance treatment with biosimilar IFX in patients with IBD is only sparse. Methods: Data from consecutive patients with CD and UC starting on biosimilar IFX between January 2015 and May 2016 at our center were analyzed. Patients were assessed as non-responders (NR), partial responders (PR), or complete responders (CR) based on clinical, endoscopic, and laboratory parameters. Besides clinical and endoscopic evaluation, C-reactive protein (CRP) levels, faecal calprotectin (FC), blood count, IFX trough levels (TL), and antibodies-to-infliximab (ATI) were measured. All adverse events were recorded. Final analysis was performed at week 54 (W54). Results: One hundred forty IBD patients (CD, 107; UC, 33) were included into the analysis. In total, 94% of CD and 82% of UC patients responded to induction therapy (W14) with biosimilar IFX. At W54 the response rates were 87% in CD and 60% in UC and 47% and 36% of patients, respectively, were in remission. Fifty two percent of UC patients experienced mucosal healing at W14 and improvement of perianal disease occurred in 96% of CD patients at W54 including 59.1% with complete cessation of drainage. Steroid-sparing effect was markedly present in all patients. Therapy was continued in 83% of patients at the end of the follow-up (89% CD and 64% UC). Trough level of at least 8.9 µg/mL at W6 was best predictive of response at W54 in both CD and UC with a sensitivity of 70.0% and specificity of 74.1% which well corresponds with the results of previous studies on original IFX. Our findings thus suggest that the same association applies also to the biosimilar IFX. Pharmacokinetic properties, immunogenicity and frequency and character of adverse events were similar to those previously observed during treatment with the original IFX. Conclusion: Biosimilar IFX after one year in naive patients with IBD patients seems to be effective and safe, gaining similar treatment results with no additional safety issues comparing to the originator.
Sa1934 EVALUATION OF TREATMENT PERSISTENCE OF VEDOLIZUMAB AMONG FINNISH INFLAMMATORY BOWEL DISEASE (IBD) PATIENTS IN REALLIFE CLINICAL PRACTICE (FINVEDO) Tero Ylisaukko-Oja, Anja Eberl, Jaakko Aaltonen, Heikki Nuutinen, Timo Blomster, Airi Jussila, Markku Pajala, Jari Jokelainen, Sauli Herrala, Klaus Tamminen, Taina SIpponen Background: Vedolizumab is a humanized immunoglobulin G1 monoclonal antibody (mAb) directed towards the integrin α4β7. Clinical trials in inflammatory bowel diseases (IBD) represent highly selected patient population and there is still limited data available of vedolizumab in real-word patient population. Therefore, we aimed to assess real-world treatment outcomes of vedolizumab in Finnish patients with IBD. Methods: This was a nationwide, retrospective, non-interventional, multi-center chart review study. All the adult (≥ 18 years of age) patients with a diagnosis of UC or CD and at least one vedolizumab infusion since the availability of the product in Finland in 2014 from 27 centers were included in the study. The exclusion criteria were the initiation of vedolizumab within < 6 months of the data collection, participation in a clinical trial during the follow-up period or planned cessation of vedolizumab treatment within 6 months from onset of treatment. Data were collected retrospectively from medical charts in a standardized case report form. The key data collection points were at baseline, week 14 and month 6 of vedolizumab treatment. The primary objective was to determine treatment persistence 6 months post initiation. Results: A total of 232 patients (CD 105, UC 127) were included. Based on Physician's Global Assessment (PGA), 101 (96.1%) CD patients had either moderately or severely active disease (Harvey-Bradshaw index mean ± SD, 12.7± 8.5; moderate disease) and 112 (92.5%) UC patients had either mildly or moderately active disease (Partial Mayo score 5.2 ±1.7; moderate disease) at baseline. Majority of the patients were treatment refractory to previous anti-TNF-alpha treatment: 97.1 % of CD patients and of 94.5 % of UC patients were anti-TNF-alpha experienced. The majority (CD 43.8%, UC, 62.2%) were using concomitant steroids at baseline (Table 1). Of all CD patients, 77 (73.3 %) and of UC patients 84 (66.1 %) were persistent on vedolizumab therapy 6 months post treatment initiation. The most common reason for discontinuation was primary lack of response (CD 63.0 %; UC 75.0 %), followed by secondary loss of response (CD 7.4 %; UC 5.0 %), adverse events (CD 14.8 %; UC 17.5 %), and other reasons (CD 18.5 %; UC 12.5 %). Conclusion: Vedolizumab provides effective and well-tolerated treatment option in a real-world clinical setting even among treatment refractory IBD patients.
Response to therapy with biosimilar infliximab at weeks 14 and 54.
AGA Abstracts
S-398
AGA Abstracts Colectomy free survival. Infliximab 5 versus 10 mg/kg induction.
Correlation of infliximab serum levels and clinical response at week 54. Box plot show comparison of median infliximab levels at week 6 between responding and non-responding groups in both CD and UC. Drug levels were compared using Mann-Whitney test.
Sa1936 INTENSIFIED INFLIXIMAB RESCUE THERAPY FOR ACUTE SEVERE ULCERATIVE COLITIS DOES NOT IMPROVE LONG TERM COLECTOMYFREE SURVIVAL Alex Al Khoury, Che-yung Chao, Talat Bessissow, Jonathan Wyse, Achuthan Aruljothy
Colectomy free survival. Short versus standard interval induction.
Background: Infliximab (IFX) is an effective rescue therapy for hospitalized steroid refractory acute ulcerative colitis (ASUC). Treatment response is associated with serum IFX trough levels. Intensified dosing regimens with escalated dose and/or shortened interval are increasingly used to compensate for the higher inflammatory burden and drug clearance. Our study aims to determine if intensified IFX induction regimen improves colectomy-free outcomes and identify predictors of long term outcomes. Methods: A retrospective review was performed between July 2010 and May 2016 at McGill University hospitals. All hospitalized adult patients who received at least one infusion of IFX as rescue therapy for steroid refractory ASUC were identified through our pharmacy drug database. We compared standard inductions with 5mg/kg vs 10mg/kg as well as shortened induction interval (i.e. completion of induction within 4 weeks). The primary outcome was the colectomy rate at 2 years. Baseline clinical parameters and dosing regimen were explored with regression analysis. Results: 72 patients (38% female, mean age 41) were identified. 37 patients (51%) received standard 5 mg/kg IFX induction and 35 received 10 mg/kg. 5 patients received shortened induction interval with IFX 10mg/kg. Baseline clinical parameters were well matched among various regimens. The 30-day and 2-year colectomy rate in our cohort was 6.9% and 15.2% respectively. 2year colectomy-free survival was not significantly different between the standard (86.5%) and escalated (82.9%) dose IFX induction (p=0.388) whereas the shortened induction was associated with lower colectomy-free rate (40% versus standard induction 88.1%, p<0.001). Hemoglobin ≤ 90 g/L (OR 4.8 [95% CI: 1.2-19.1], p=0.03), albumin < 30 g/L (OR 7.9 [95% CI: 1.5-40.1], p=0.01) and a short IFX induction regimen (OR 11.1 [95% CI: 1.676.6], p=0.015) were all associated with increased risk of colectomy at 2 years in univariate regression analysis. Albumin < 30 g/L remained significant in multivariate modelling (p= 0.03). Conclusion: Use of intensified infliximab rescue therapy did not improve 2-year colectomy-free survival in this cohort. Tailored use in high risk patients such as those with low albumin and hemoglobin may be beneficial although this needs to be validated in prospective clinical trials.
Sa1937 EXCLUSIVE ENTERAL NUTRITION IN ADULTS WITH ACTIVE CROHN'S DISEASE IS ASSOCIATED WITH DECREASED DISEASE ACTIVITY Tamar Pfeffer-Gik, Henit A. Yanai, Lihi Godny, Yulia Ron, Nitsan Maharshak, Iris Dotan Background: Exclusive Enteral Nutrition (EEN) for 8-12 weeks, induces clinical remission in ~70% of children and adolescents with active Crohn's disease (CD), and is considered comparable to steroids. We aimed to evaluate the impact of EEN in adults with active CD. Methods: Patients with active CD, referred for nutritional intervention with EEN in a tertiary inflammatory bowel disease (IBD) center, were enrolled. Baseline weight and nutritional needs were recorded. EEN was administered by oral polymeric formula with no other food items allowed. Patients were treated for at least three weeks. Physician's Global assessment (PGA), Harvey Bradshaw Index (HBI), biomarkers (blood count, C-reactive protein [CRP], and albumin), weight, and body mass index (BMI) were recorded at baseline and at the end of EEN course. Results: A total of 33/42 patients with active CD (78%) who were offered EEN completed a full course. Eleven patients (33.3%) had newly diagnosed CD (<1.5 years), 16 (48.5%) were on stable-dose medications (immunomodulators and/or biologics), and two (6%) had no medical treatment. Disposition: male/female 25/8 ; mean age: 31.7±9.4 years; median disease duration - 7 (IQR 1-16) years. Montreal classification: L1 13 (39.4%),L2- 1 (3%) L3 - 18 (54.5%); B1-15 (45.5%), B2 -10 (30.3%), B3 - 4 (12.1%); P - 8 (24.2%). Baseline disease activity: PGA - mild-4, -moderate-20, and severe-8; mean HBI 6.7 ± 4.7 points; median CRP 2.0 mg/dl (IQR 1.3-5.6). Mean EEN duration was 5.5 weeks (range 3-16). Baseline PGA improved after the EEN course in 31/33 patients (94%), this was in parallel to improvement in all activity indices: HBI 2.65±2.7 vs 6.78±4.7 vs (p<0.001); median CRP 1.01 (IQR 0.4-0.7) mg/dl vs 2 (IQR 1.3-5.6) vs mg/dl (p<0.001); mean albumin 4.2±0.4 mg/l vs 3.8±0.6 mg/l (p=0.003), respectively. There was no change in weight or BMI during EEN therapy. Notably, activity indices were also improved in a subgroup of long standing- CD patients: decrease in HBI 7.3±5.08 to 3.0±3.4 (p<0.001); CRP 4.66±5.7 mg/dl to 1.08±1.5 mg/dl (p=0.005). Finally, in 16 patients who received EEN as an add- on therapy to stable doses of their baseline therapy, HBI decreased from 6.5±5.8 to 2.4±3.3 (p=0.001) and CRP dropped from 3.5 (IQR 0.98-3.6) mg/dl to 0.88 (IQR 0.360.6)mg/dl (p=0.023). Conclusion: EEN is an effective therapeutic modality for active CD in adults. EEN therapy is associated with decreased clinical and biologic inflammatory activity, and may benefit patients with longstanding and newly diagnosed CD in need of a bridge or an add-on induction treatment.
S-399
AGA Abstracts
AGA Abstracts
COMBINATION THERAPY OF VEDOLIZUMAB AND A TNF ANTAGONIST IN IBD PATIENTS WITH SEVERE CHRONIC ACTIVE, THERAPY REFRACTORY DISEASE COURSE Tanja Kuehbacher, Raed AbuHashem, Natalie Langel, Stefan Schreiber, Oliver Drvarov Background: Vedolizumab and TNF antagonists are biologicals with different modes of action.Vedolizumab a humanized monoclonal antibody that specifically binds to the a4b7 integrin, blocks the interaction of the a4b7 integrin with MAdCAM-1 and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue. TNF antagonists neutralize the proinflammatory cytokine TNF, but the mode of action still remains unclear. Induction of mucosal T-cell apoptosis and downregulation of proinflammatory cytokines are only some of the identified mechanisms. 50% of IBD patients have a chronic active course of disease. Some of them suffer from a severe, so far therapy refractory disease course. A combination therapy of different biologicals might be effective in these patients. Methods: 7 patients with IBD (4 with Crohns Disease and 3 with ulcerative colitis) were treated with vedolizumab in combination with a TNF antagonist as an individual healing attempt through a case by case decision. Patients were seen as standard clinical care at baseline, week 2, 6, 14 and week 30. CDAI, CRP and calprotectin were assessed at all visits. Sonography and ileocolonoscopy or sigmoidoscopy (in ulcerative colitis patients) was performed at baseline, week 14 and week 30. SES-CDEIS and complete Mayo score was assed also at baseline, week 14 and week 30. Results: Mean CDAI at baseline: 410 (CD), Mayo score 11 (UC), CRP 39.76 mg/l (both UC and CD), fecal calprotectin 2100 mg/kg (UC), 883(CD), SES-CDEIS 31 (CD). CRP at week 2: and 6: 35.74 mg/l and 21.21 mg/l (both UC and CD), calprotectin at week 2 and 6: 1956 mg/kg (UC), 798 (CD), 1287 mg/kg (UC), 580 (CD). Mean CDAI at week 2 and 6: 404 and 383 (CD). Mean CDAI at week 14: 262 (CD), Mayo score 8 (UC), CRP 15.71 mg/l (both UC and CD), fecal calprotectin 760 mg/kg (UC), 465(CD), SES-CDEIS 22 (CD). Mean CDAI at week 30: 172 (CD), Mayo score 4 (UC), CRP 3.46 mg/l (both UC and CD), fecal calprotectin 377 mg/kg (UC), 215(CD), SES-CDEIS 11 (CD). Even so none of the patients were in complete deep remission, a significantly improvement could be seen in disease symptoms like abdominal pain and stool frequency and a significant improvement in the mucosal inflammation could be assessed by endoscopy. Conclusions: Combination therapy was well tolerated and effective. No severe infections or other severe adverse events could be seen so far. Further and larger clinical trials have to be performed in the future to investigate the efficacy and safety of anti-integrin antibodies and TNF antagonists as a combination therapy for a fast remission induction or as a maintenance combination therapy.
Table 1. Baseline characteristics.
Sa1935 BIOSIMILAR INFLIXIMAB IN ANTI-TNF NAIVE IBD PATIENTS AND ONEYEAR CLINICAL FOLLOW-UP Martin Kolar, Dana Duricova, Martin Bortlik, Veronika Hruba, Nadezda Machkova, Katarina Mitrova, Martin Lukas, Karin Malickova, Milan Lukas Background: First biosimilar infliximab (IFX) has been approved in European Union for treatment of inflammatory bowel disease (IBD) since September 2013. The approval process included extrapolation of clinical data from other indications, namely rheumatoid arthritis and ankylosing spondylitis. Data from clinical practice are therefore desirable to confirm efficacy and safety of biosimilar IFX in IBD population. Despite growing data on early treatment results, the evidence on long-term efficiency and safety of maintenance treatment with biosimilar IFX in patients with IBD is only sparse. Methods: Data from consecutive patients with CD and UC starting on biosimilar IFX between January 2015 and May 2016 at our center were analyzed. Patients were assessed as non-responders (NR), partial responders (PR), or complete responders (CR) based on clinical, endoscopic, and laboratory parameters. Besides clinical and endoscopic evaluation, C-reactive protein (CRP) levels, faecal calprotectin (FC), blood count, IFX trough levels (TL), and antibodies-to-infliximab (ATI) were measured. All adverse events were recorded. Final analysis was performed at week 54 (W54). Results: One hundred forty IBD patients (CD, 107; UC, 33) were included into the analysis. In total, 94% of CD and 82% of UC patients responded to induction therapy (W14) with biosimilar IFX. At W54 the response rates were 87% in CD and 60% in UC and 47% and 36% of patients, respectively, were in remission. Fifty two percent of UC patients experienced mucosal healing at W14 and improvement of perianal disease occurred in 96% of CD patients at W54 including 59.1% with complete cessation of drainage. Steroid-sparing effect was markedly present in all patients. Therapy was continued in 83% of patients at the end of the follow-up (89% CD and 64% UC). Trough level of at least 8.9 µg/mL at W6 was best predictive of response at W54 in both CD and UC with a sensitivity of 70.0% and specificity of 74.1% which well corresponds with the results of previous studies on original IFX. Our findings thus suggest that the same association applies also to the biosimilar IFX. Pharmacokinetic properties, immunogenicity and frequency and character of adverse events were similar to those previously observed during treatment with the original IFX. Conclusion: Biosimilar IFX after one year in naive patients with IBD patients seems to be effective and safe, gaining similar treatment results with no additional safety issues comparing to the originator.
Sa1934 EVALUATION OF TREATMENT PERSISTENCE OF VEDOLIZUMAB AMONG FINNISH INFLAMMATORY BOWEL DISEASE (IBD) PATIENTS IN REALLIFE CLINICAL PRACTICE (FINVEDO) Tero Ylisaukko-Oja, Anja Eberl, Jaakko Aaltonen, Heikki Nuutinen, Timo Blomster, Airi Jussila, Markku Pajala, Jari Jokelainen, Sauli Herrala, Klaus Tamminen, Taina SIpponen Background: Vedolizumab is a humanized immunoglobulin G1 monoclonal antibody (mAb) directed towards the integrin α4β7. Clinical trials in inflammatory bowel diseases (IBD) represent highly selected patient population and there is still limited data available of vedolizumab in real-word patient population. Therefore, we aimed to assess real-world treatment outcomes of vedolizumab in Finnish patients with IBD. Methods: This was a nationwide, retrospective, non-interventional, multi-center chart review study. All the adult (≥ 18 years of age) patients with a diagnosis of UC or CD and at least one vedolizumab infusion since the availability of the product in Finland in 2014 from 27 centers were included in the study. The exclusion criteria were the initiation of vedolizumab within < 6 months of the data collection, participation in a clinical trial during the follow-up period or planned cessation of vedolizumab treatment within 6 months from onset of treatment. Data were collected retrospectively from medical charts in a standardized case report form. The key data collection points were at baseline, week 14 and month 6 of vedolizumab treatment. The primary objective was to determine treatment persistence 6 months post initiation. Results: A total of 232 patients (CD 105, UC 127) were included. Based on Physician's Global Assessment (PGA), 101 (96.1%) CD patients had either moderately or severely active disease (Harvey-Bradshaw index mean ± SD, 12.7± 8.5; moderate disease) and 112 (92.5%) UC patients had either mildly or moderately active disease (Partial Mayo score 5.2 ±1.7; moderate disease) at baseline. Majority of the patients were treatment refractory to previous anti-TNF-alpha treatment: 97.1 % of CD patients and of 94.5 % of UC patients were anti-TNF-alpha experienced. The majority (CD 43.8%, UC, 62.2%) were using concomitant steroids at baseline (Table 1). Of all CD patients, 77 (73.3 %) and of UC patients 84 (66.1 %) were persistent on vedolizumab therapy 6 months post treatment initiation. The most common reason for discontinuation was primary lack of response (CD 63.0 %; UC 75.0 %), followed by secondary loss of response (CD 7.4 %; UC 5.0 %), adverse events (CD 14.8 %; UC 17.5 %), and other reasons (CD 18.5 %; UC 12.5 %). Conclusion: Vedolizumab provides effective and well-tolerated treatment option in a real-world clinical setting even among treatment refractory IBD patients.
Response to therapy with biosimilar infliximab at weeks 14 and 54.
AGA Abstracts
S-398
AGA Abstracts Colectomy free survival. Infliximab 5 versus 10 mg/kg induction.
Correlation of infliximab serum levels and clinical response at week 54. Box plot show comparison of median infliximab levels at week 6 between responding and non-responding groups in both CD and UC. Drug levels were compared using Mann-Whitney test.
Sa1936 INTENSIFIED INFLIXIMAB RESCUE THERAPY FOR ACUTE SEVERE ULCERATIVE COLITIS DOES NOT IMPROVE LONG TERM COLECTOMYFREE SURVIVAL Alex Al Khoury, Che-yung Chao, Talat Bessissow, Jonathan Wyse, Achuthan Aruljothy
Colectomy free survival. Short versus standard interval induction.
Background: Infliximab (IFX) is an effective rescue therapy for hospitalized steroid refractory acute ulcerative colitis (ASUC). Treatment response is associated with serum IFX trough levels. Intensified dosing regimens with escalated dose and/or shortened interval are increasingly used to compensate for the higher inflammatory burden and drug clearance. Our study aims to determine if intensified IFX induction regimen improves colectomy-free outcomes and identify predictors of long term outcomes. Methods: A retrospective review was performed between July 2010 and May 2016 at McGill University hospitals. All hospitalized adult patients who received at least one infusion of IFX as rescue therapy for steroid refractory ASUC were identified through our pharmacy drug database. We compared standard inductions with 5mg/kg vs 10mg/kg as well as shortened induction interval (i.e. completion of induction within 4 weeks). The primary outcome was the colectomy rate at 2 years. Baseline clinical parameters and dosing regimen were explored with regression analysis. Results: 72 patients (38% female, mean age 41) were identified. 37 patients (51%) received standard 5 mg/kg IFX induction and 35 received 10 mg/kg. 5 patients received shortened induction interval with IFX 10mg/kg. Baseline clinical parameters were well matched among various regimens. The 30-day and 2-year colectomy rate in our cohort was 6.9% and 15.2% respectively. 2year colectomy-free survival was not significantly different between the standard (86.5%) and escalated (82.9%) dose IFX induction (p=0.388) whereas the shortened induction was associated with lower colectomy-free rate (40% versus standard induction 88.1%, p<0.001). Hemoglobin ≤ 90 g/L (OR 4.8 [95% CI: 1.2-19.1], p=0.03), albumin < 30 g/L (OR 7.9 [95% CI: 1.5-40.1], p=0.01) and a short IFX induction regimen (OR 11.1 [95% CI: 1.676.6], p=0.015) were all associated with increased risk of colectomy at 2 years in univariate regression analysis. Albumin < 30 g/L remained significant in multivariate modelling (p= 0.03). Conclusion: Use of intensified infliximab rescue therapy did not improve 2-year colectomy-free survival in this cohort. Tailored use in high risk patients such as those with low albumin and hemoglobin may be beneficial although this needs to be validated in prospective clinical trials.
Sa1937 EXCLUSIVE ENTERAL NUTRITION IN ADULTS WITH ACTIVE CROHN'S DISEASE IS ASSOCIATED WITH DECREASED DISEASE ACTIVITY Tamar Pfeffer-Gik, Henit A. Yanai, Lihi Godny, Yulia Ron, Nitsan Maharshak, Iris Dotan Background: Exclusive Enteral Nutrition (EEN) for 8-12 weeks, induces clinical remission in ~70% of children and adolescents with active Crohn's disease (CD), and is considered comparable to steroids. We aimed to evaluate the impact of EEN in adults with active CD. Methods: Patients with active CD, referred for nutritional intervention with EEN in a tertiary inflammatory bowel disease (IBD) center, were enrolled. Baseline weight and nutritional needs were recorded. EEN was administered by oral polymeric formula with no other food items allowed. Patients were treated for at least three weeks. Physician's Global assessment (PGA), Harvey Bradshaw Index (HBI), biomarkers (blood count, C-reactive protein [CRP], and albumin), weight, and body mass index (BMI) were recorded at baseline and at the end of EEN course. Results: A total of 33/42 patients with active CD (78%) who were offered EEN completed a full course. Eleven patients (33.3%) had newly diagnosed CD (<1.5 years), 16 (48.5%) were on stable-dose medications (immunomodulators and/or biologics), and two (6%) had no medical treatment. Disposition: male/female 25/8 ; mean age: 31.7±9.4 years; median disease duration - 7 (IQR 1-16) years. Montreal classification: L1 13 (39.4%),L2- 1 (3%) L3 - 18 (54.5%); B1-15 (45.5%), B2 -10 (30.3%), B3 - 4 (12.1%); P - 8 (24.2%). Baseline disease activity: PGA - mild-4, -moderate-20, and severe-8; mean HBI 6.7 ± 4.7 points; median CRP 2.0 mg/dl (IQR 1.3-5.6). Mean EEN duration was 5.5 weeks (range 3-16). Baseline PGA improved after the EEN course in 31/33 patients (94%), this was in parallel to improvement in all activity indices: HBI 2.65±2.7 vs 6.78±4.7 vs (p<0.001); median CRP 1.01 (IQR 0.4-0.7) mg/dl vs 2 (IQR 1.3-5.6) vs mg/dl (p<0.001); mean albumin 4.2±0.4 mg/l vs 3.8±0.6 mg/l (p=0.003), respectively. There was no change in weight or BMI during EEN therapy. Notably, activity indices were also improved in a subgroup of long standing- CD patients: decrease in HBI 7.3±5.08 to 3.0±3.4 (p<0.001); CRP 4.66±5.7 mg/dl to 1.08±1.5 mg/dl (p=0.005). Finally, in 16 patients who received EEN as an add- on therapy to stable doses of their baseline therapy, HBI decreased from 6.5±5.8 to 2.4±3.3 (p=0.001) and CRP dropped from 3.5 (IQR 0.98-3.6) mg/dl to 0.88 (IQR 0.360.6)mg/dl (p=0.023). Conclusion: EEN is an effective therapeutic modality for active CD in adults. EEN therapy is associated with decreased clinical and biologic inflammatory activity, and may benefit patients with longstanding and newly diagnosed CD in need of a bridge or an add-on induction treatment.
S-399
AGA Abstracts