Late breaking abstracts
2019; Wiley; Volume: 7; Issue: 10 Linguagem: Inglês
10.1177/2050640619888859
ISSN2050-6414
Tópico(s)Esophageal and GI Pathology
ResumoUnited European Gastroenterology JournalVolume 7, Issue 10 p. 1411-1425 Late breaking abstractOpen Access Late breaking abstracts First published: 01 December 2019 https://doi.org/10.1177/2050640619888859AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat 14:00–15:30 / F3 IBD Highlights LB01 EFFICACY AND SAFETY OF USTEKINUMAB FOR ULCERATIVE COLITIS THROUGH 2 YEARS: UNIFI LONG-TERM EXTENSION B.E. Sands1, W.J. Sandborn2, R. Panaccione3, C. O’Brien4, H. Zhang4, J. Johanns4, Y. Zhou4, I. Tikhonov4, L. Peyrin-Biroulet5, G. Van Assche6, S. Danese7, S. Targan8, M.T. Abreu9, T. Hisamatsu10, E. Scherl11, R.W. Leong12, D. Rowbotham13, R.P. Arasaradnam14, C. Marano4 1Icahn School of Medicine at Mount Sinai, Division Of Gastroenterology, New York, United States 2University of California San Diego, San Diego, United States 3University of Calgary, Medicine, Calgary, Canada 4Janssen Research & Development, LLC, Spring House, United States 5Nancy University Hospital, Vandoeuvre, France 6University of Leuven Division of Gastroenterology University Hospitals Leuven, Leuven, Belgium 7Humanitas University/ Humanitas Research Hospital, Milano, Italy 8Cedars-Sinai Medical Center, Los Angeles, United States 9University of Miami, Miller School of Medicine, Crohn's and Colitis Center, Miami, United States 10Kyorin University School of Medicine, Tokyo, Japan 11Weill Cornell Medical Center, New York Presbyterian, New York, United States 12Concord Repatriation General Hospital, Concord, Australia 13Auckland City Hospital, Gastroenterology & Hepatology, Auckland, New Zealand 14University Hospital Coventry and Warwickshire, Dept. of Gastroenterology, Coventry, United Kingdom Contact E-Mail Address: bruce.sands@mssm.edu Introduction: Ustekinumab (UST) is a fully human immunoglobulin G1κ mAB antagonist to IL-12/23p40 for moderately to severely active ulcerative colitis (UC). The ongoing UNIFI long-term extension (LTE) evaluates subcutaneous (SC) UST through 220wks of maintenance treatment, with efficacy (wk92) and safety (wk96) results for patients treated in the LTE reported here. Aims & Methods: 783 patients entered the maintenance study, including 523 intravenous (IV) UST induction responders in the primary population (randomized to SC placebo [PBO]; n = 175, UST 90 mg every 12 weeks [q12w]; n = 172, or UST 90 mg q8w; n = 176). Non-randomized patients included UST delayed responders (patients in clinical response to UST following an IV & SC UST dose) who received SC UST 90 mg q8w and PBO responders who received SC PBO. All patients completing wk44 were eligible to enter the LTE. PBO patients were discontinued after wk44 unblinding. Efficacy measures (i.e. partial Mayo scores and fecal inflammatory biomarkers) were collected every 12wks, thereafter at each dosing visit. Safety was evaluated throughout. Results: 588 patients were treated in the LTE, including 284 receiving SC UST and 115 receiving SC PBO in the randomized population and 116 UST delayed responders and 73 PBO responders. Rates of discontinuation before wk96 among randomized patients treated in LTE were 8.5% for UST and 40.9% for PBO. Among randomized patients who continued to receive UST in the LTE, percentages of patients in symptomatic remission from wks44 to 92 or up to the time of dose adjustment (as observed) ranged from 72.1% to 81.9% in the q12w group and 77.3% to 87.6% in the q8w group; percentages in partial Mayo remission ranged from 72.1% to 83.8% and 78.0% to 89.4%, respectively. In the ITT analysis of patients who were treated in the LTE, 60.6% and 62.0% of patients in the combined UST group attained symptomatic and partial Mayo steroid-free remission, respectively, at wk92 (Table). Among patients who had achieved clinical remission at maintenance baseline, 73.1% and 74.6% of patients in the combined UST group attained symptomatic and partial Mayo remission, respectively, at both wks 44 and 92. Among all patients treated in the LTE, those treated with UST had 428.3 patient-years of follow-up vs. 134.0 patient-years for PBO from wks44–92. Safety events per hundred patient-years of follow-up from wks44–92 for combined UST vs. PBO were AEs: 255.68 vs. 267.93, SAEs: 9.34 vs. 12.69, and serious infections: 2.33 vs. 2.99. One UST-treated patient experienced failure to thrive and ultimately expired due to cardiac arrest. Malignancy rates were low and similar between groups: lentigo malignant melanoma in situ (PBO only); BCC (1 PBO with prior UST during induction, 1 q12w and 2 q8w [1 q8w presented with SCC]). Conclusion: The efficacy of UST in patients with UC was sustained through 92wks. No new safety signals were observed. [Number of patients with clinical outcomes through Week 92 (ITT analysis); randomized patients in the maintenance study who were treated in the LTE] Disclosure: This study was funded by Janssen Research & Development, LLC. Drs. Sands, Sandborn, Panaccione, Peyrin-Biroulet, Van Assche, Danese, Targan, Abreu, Hisamatsu, Scherl, Leong, Rowbotham, and Arasaradnam have been investigators for trials sponsored by Janssen and/or have received consulting fees from Janssen. Drs. O’Brien, Zhang, Johanns, Zhou, Tikhonov, and Marano are Janssen employees and own stock and/or stock options in Johnson & Johnson. Abstract No: LB01 Clinical outcome UST 90 mg SC q12wa (N = 141) UST 90 mg SC q8wa (N = 143) UST Combined (N = 284) Corticosteroid-free symptomatic remission at Week 92b,c,d 83 (58.9%) 89 (62.2%) 172 (60.6%) Corticosteroid-free partial Mayo remission at Week 92c,d,e 86 (61.0%) 90 (62.9%) 176 (62.0%) Patients receiving concomitant corticosteroids at maintenance baseline 68 (48.2%) 71 (49.7%) 139 (48.9%) Corticosteroid-free symptomatic remission at Week 92b,c,d,f 34 (50.0%) 41 (57.7%) 75 (54.0%) Corticosteroid-free partial Mayo remission at Week 92c,d,e,f 36 (52.9%) 42 (59.2%) 78 (56.1%) Patients who had achieved clinical remissiong at maintenance baseline 35 (24.8%) 32 (22.4%) 67 (23.6%) Symptomatic remission at both Week 44 and Week 92b,c,h 27 (77.1%) 22 (68.8%) 49 (73.1%) Partial Mayo remission at both Week 44 and Week 92b,e,h 27 (77.1%) 23 (71.9%) 50 (74.6%) a Randomized group at maintenance Week 0, regardless of whether patients had a dose adjustment during the LTE. b Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. Patients who had both stool frequency and rectal bleeding subscores missing at a visit were considered not to be in symptomatic remission for that visit. c Patients who had an ostomy or colectomy, or discontinued study agent due to lack of therapeutic effect or due to an AE of worsening of UC or were dose adjusted (only occurred from Week 56 onward) prior to the designated visit, were considered not to be in symptomatic or partial Mayo remission from the time of the event onward. d Patients who had a missing value in corticosteroid use had their last value carried forward. e Partial Mayo remission is defined as a partial Mayo score ≤ 2. Patients who had all 3 partial Mayo subscores missing at a visit were considered not to be in partial Mayo remission for that visit. f Denominator is the number of patients who were receiving concomitant corticosteroids at maintenance baseline. g Clinical remission is defined as a Mayo score ≤2 points, with no individual subscore >1. h Denominator is the number of patients who had achieved clinical remission at maintenance baseline. Key: AE, adverse event; SC, subcutaneous; q8w, every 8 weeks; q12w, every 12 weeks; UC, ulcerative colitis. LB02 NONINFERIORITY OF NOVEL SUBCUTANEOUS INFLIXIMAB (CT-P13) TO INTRAVENOUS INFLIXIMAB (CT-P13) IN PATIENTS WITH ACTIVE CROHN’S DISEASE AND ULCERATIVE COLITIS: WEEK 30 RESULTS FROM A MULTICENTRE, RANDOMISED CONTROLLED PIVOTAL TRIAL S. Schreiber1, J. Leszczyszyn2, R. Dudkowiak2, A. Lahat3, B. Gawdis-Wojnarska4, A. Pukitis5, M. Horynski6, K. Farkas7, J. Kierkus8, M. Kowalski9, S. Ben-Horin10, B.D. Ye11, S.J. Lee12, S.H. Kim12, M.R. Kim12, H.N. Kim12, W. Reinisch13 1University Hospital Schleswig-Holstein, Kiel, Germany 2Melita Medical, Wroclaw, Poland 3Chaim Sheba Medical Center and Sackler School of Medicine Tel Aviv University, Ramat Gan, Israel 4Twoja Przychodnia – Szczecińskie Centrum Medyczne, Szczecin, Poland 5Pauls Stradins Clinical University Hospital, Riga, Latvia 6Endoskopia Sp. z o.o., Sopot, Poland 7Szent Imre Egyetemi Oktatókórház, Budapest, Hungary 8Centrum Zdrowia Dziecka, Warsaw, Poland 9Centrum Diagnostyczno – Lecznicze Barska Sp. z o.o., Wloclawek, Poland 10University of Tel Aviv Sheba Medical Center, Tel-Hashomer, Israel 11University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (Republic of) 12CELLTRION, INC, Incheon, Korea (Republic of) 13Medical University of Vienna, Vienna, Austria Contact E-Mail Address: s.schreiber@mucosa.de Introduction: CT-P13 subcutaneous (SC) formulation was developed to augment the flexibility in therapeutic use of infliximab dependent upon need of drug exposure, and also provide patients with expanded, convenient options for chronic therapy which would boost up their quality of life. CT-P13 SC showed comparable efficacy and safety with CT-P13 intravenous (IV) in preliminary studies of Crohn's disease (CD)1 and rheumatoid arthritis (RA)2. Noninferiority (NI) of CT-P13 SC was demonstrated for efficacy in RA patients3. Aims & Methods: This randomised, controlled, open-label, multicentre study aimed to demonstrate NI of CT-P13 SC compared with CT-P13 IV in terms of pharmacokinetics (PK), and evaluate efficacy and safety in a mixed population of active CD (Crohn's Disease Activity Index [CDAI] score of 220 to 450) and ulcerative colitis (UC) (total Mayo score of 6 to 12 with endoscopic subscore of ≥2). After loading doses of IV 5 mg/kg at Weeks 0 and 2, patients were randomised at Week 6 to receive either SC 120 mg (<80 kg) or 240 mg (≥80 kg) every 2 weeks (SC arm), or IV 5 mg/kg every 8 weeks (IV arm). The primary PK endpoint, Ctrough,week22 (pre-dose serum concentration at Week 22), was analysed by using analysis of covariance (ANCOVA). The NI of SC (120 mg and 240 mg combined) was predefined to be met if the lower bound of the 2-sided 90% confidence interval (CI) for the ratio of the geometric least square (LS) means was higher than 80%. Comparative clinical efficacy and safety profiles were assessed for both arms. Results: In total, 136 patients were enrolled and 131 were randomised (66 to SC and 65 to IV). The primary endpoint, NI of SC compared with IV in terms of Ctrough,week22, was achieved as the lower bound of 90% CI for the ratio of the geometric LS means (786.37–1694.00%) was greater than 80%, with higher geometric LS mean of Ctrough,week22 in SC (20.9844 µg/mL in SC and 1.8181 µg/mL in IV). Frequent administration of small doses and delayed absorption of SC led to more constant exposure compared with IV dosing. Combined clinical remission rates for CD and UC patients at Week 30 were comparable between the 2 arms (66.7% [44/66 patients] in SC and 54.7% [35/64 patients] in IV, p = 0.1620). Mucosal healing at Week 22 was achieved as SES-CD score ≤2 for CD and Mayo endoscopic subscore ≤1 for UC, also comparably between the 2 arms (48.1% [26/54 patients] in SC and 41.0% [16/39 patients] in IV, p = 0.4958). The safety profiles after randomisation were generally comparable between the two arms. Localised injection site reactions occurred more commonly in SC but all were grade 1 or 2 in intensity. The anti-drug antibody positive rate was slightly lower in SC at Week 30 (37.9% [25/66 patients] in SC and 53.8% [35/65 patients] in IV). Conclusion: Administration of CT-P13 SC resulted in a noninferior drug exposure in comparison with CT-P13 IV in moderately to severely active inflammatory bowel disease patients. CT-P13 SC resulted in adequate trough level, achieving comparable clinical efficacy between the two formulations. It is anticipated that this novel formulation would facilitate and broaden access to efficacious and convenient therapy for the patients. Disclosure: Schreiber S. receives personal fees from Abbvie, Arena, BMS, Biogen, Celltrion Inc., Celgene, IMAB, Gilead, MSD, Mylan, Pfizer, Fresenius, Janssen, Takeda, Theravance, Provention Bio, Protagonist and Falk, outside the submitted work. Leszczyszyn J., Dudkowiak R., Lahat A., Gawdis-Wojnarska B., Pukitis A., Horynski M., Farkas K., Kierkus J., and Kowalski M. have nothing to disclose. Ben-Horin S. receives consultancy/advisory board fees from Janssen, Takeda, Celltrion Inc., Abbvie, Ferring, Pfizer, GSK and research support from Takeda, Abbvie, Celltrion, Pfizer and Janssen. Ye B. D. receives research grant from Celltrion Inc., consulting fees from Abbvie Korea, Chong Kun Dang Pharm., Daewoong Pharma, Ferring Korea, Janssen Korea, Kangstem Biotech, Kuhnil Pharm., Shire Korea, Takeda Korea, IQVIA, Cornerstones Health, Robarts Clinical Trials Inc. and Takeda, speaking fees from Abbvie Korea, Celltrion Inc., Janssen Korea, Shire Korea, Takeda Korea and IQVIA. Lee S. J., Kim S. H., Kim M. R., and Kim H. N. are employees of Celltrion Inc. Reinisch W. receives personal fees as a speaker for Abbott Laboratories, Abbvie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor, Yakult, as a consultant for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Avaxia, Roland Berger GmBH, Bioclinica, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, Elan, Eli Lilly, Ernest & Young, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, LivaNova, Mallinckrodt, Medahead, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nash Pharmaceuticals, Nestle, Nippon Kayaku, Novartis, Ocera, Otsuka, Parexel, PDL, Periconsulting, Pharmacosmos, Philip Morris Institute, Pfizer, Procter & Gamble, Prometheus, Protagonist, Provention, Robarts Clinical Trial, Sandoz, Schering-Plough, Second Genome, Seres Therapeutics, Setpointmedical, Sigmoid, Takeda, Therakos, Tigenix, UCB, Vifor, Zealand, Zyngenia, and 4SC, as an advisory board member for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zealand, Zyngenia, and 4SC, and has received research funding from Abbott Laboratories, Abbvie, Aesca, Centocor, Falk Pharma GmbH, Immundiagnsotik, MSD. References Ye BD, et al. Tu1715 A Novel Formulation of CT-P13 (Infliximab Biosimilar) for Subcutaneous Administration: 1-Year Result from a Phase I Open-Label Randomized Controlled Trial in Patients with Active Crohn's Disease. Gastroenterology 2019; 156(6). Yoo DH, et al. Fri0128 A Novel Formulation of CT-P13 (Infliximab Biosimilar) for Subcutaneous Administration: 1-Year Results from a Part 1 of Phase I/III Randomized Controlled Trial in Patients with Active Rheumatoid Arthritis. Poster Presentations. 2019. Westhovens R, et al. Sat0170 A Novel Formulation of CT-P13 for Subcutaneous Administration: 30 Week Results from a Part 2 of Phase I/III Randomized Controlled Trial in Patients with Rheumatoid Arthritis. 2019. Abstract No: LB02 PK (Ctrough,week22) SC 120/240 mg (N = 59) IV 5 mg/kg (N = 57) Efficacy (CD) SC 120/240 mg (N = 28) IV 5 mg/kg (N = 25) Geometric least square mean 20.9844 µg/mL 1.8181 µg/mL CDAI score, mean (SD) Baseline: 296.4 (59.21) W6: 165.0 (96.36) W22: 106.6 (80.46) W30: 103.8 (88.44) Baseline: 294.8 (59.90) W6: 144.9 (80.12) W22: 105.1 (60.97) W30: 106.4 (67.71) Ratio of geometric least square means (90% confidence interval) 1154.17 (786.37–1694.00) % Clinical response1, n (%) W6: 21 (75.0) W22: 22 (78.6) W30: 19 (67.9) W6: 21 (84.0) W22: 21 (84.0) W30: 17 (68.0) Safety (W6∼30), n (%) SC 120/240 mg (N = 66) IV 5 mg/kg (N = 65) Clinical remission2, n (%) W6: 14 (50.0) W22: 17 (60.7) W30: 18 (64.3) W6: 12 (48.0) W22: 15 (60.0) W30: 14 (56.0) Treatment-emergent adverse events 39 (59.1) 34 (52.3) Efficacy (UC) SC 120/240 mg (N = 38) IV 5 mg/kg (N = 39) Infusion related/ systemic injection reactions 1 (1.5) 2 (3.1) Partial Mayo score3, mean (SD) Baseline: 5.4 (1.31) W6: 2.6 (2.13) W22: 1.3 (1.63) W30: 1.2 (1.59) Baseline: 5.9 (1.21) W6: 2.5 (1.74) W22: 2.3 (1.97) W30: 1.9 (1.88) Localised injection site reactions 11 (16.7) 2 (3.1) Clinical response4, n (%) W6: 28 (73.7) W22: 32 (84.2) W30: 33 (86.8) W6: 31 (79.5) W22: 30 (76.9) W30: 29 (74.4) Infections 13 (19.7) 11 (16.9) Clinical remission5, n (%) W6: 14 (36.8) W22: 23 (60.5) W30: 26 (68.4) W6: 12 (30.8) W22: 15 (38.5) W30: 21 (53.8) Note: Randomisation at Week 6 to treatment assignment was stratified by concomitant use of immunomodulators, disease (CD or UC), clinical response at Week 6 (responder or nonresponder by CDAI-70 for CD and partial Mayo score for UC), and body weight at Week 6 (<80 kg or ≥80 kg). 1. Patients with decrease in CDAI score of 70 points or more from the baseline value. 2. Patients with CDAI score of less than 150 points. 3. Partial Mayo score was composed of stool frequency, rectal bleeding and physician's global assessment. 4. Patients with decrease in partial Mayo score from baseline at least 2 points, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point, or an absolute subscore for rectal bleeding of 0 or 1. 5. Patients with partial Mayo score of 1 point or lower. [Clinical results up to Week 30] LB03 MICROVILLI LENGTH PREDICTS CLINICAL RESPONSE TO USTEKINUMAB IN CROHN’S PATIENTS FROM THE UNITI-2 TRIAL K. Van Dussen1, K. Li2, K. Simpson3, B. Claggett4, J. Friedman5, J. Perrigoue5, T. Stappenbeck6 1University of Cincinnati College of Medicine, Pediatrics, Cincinnati, United States 2Janssen Research & Development, Spring House, United States 3Washington University School of Medicine, Pathology and Immunology, St. Louis, United States 4Harvard Medical School, Boston, United States 5Janssen Research & Development, Immunology, Spring House, United States 6Washington University Medical School, Department of Pathology and Immunology, St. Louis, United States Contact E-Mail Address: stappenb@wustl.edu Introduction: Mucosal biomarkers have been shown to identify responders to anti-TNF and anti-integrin therapies in Crohn's Disease (CD) patients. We have recently identified a novel epithelial biomarker of malabsorption, microvilli (MV) length, to be significantly reduced in CD patients. We hypothesize that malabsorption contributes to the development of intestinal inflammation and therefore may have predictive value for clinical and endoscopic response to biologic therapy in CD patients. Ustekinumab (UST) is an anti-IL12/23 monoclonal antibody approved for the treatment of CD. Aims & Methods: The aim of this study was to determine the predictive value of pre-treatment ileal biopsy MV length for clinical and endoscopic response to UST in CD patients. Biopsy samples from the American cohort of UNITI-2 trial patients were stained for H&E and analyzed for MV length. Clinical response, defined as a reduction of CDAI of ≥100 points from pre-treatment baseline, clinical remission, defined as CDAI < 150, and endoscopic response, defined as ≥50% reduction from baseline SES-CD score, at 8 weeks post-induction were assessed. The primary outcome was clinical response to UST stratified by reduction in pre-treatment MV length, using a threshold of 1.7 µm (normal above, low below). Outcomes were compared using Fisher exact tests for subgroups and likelihood ratio tests for tests of effect modification. Results: A total of 106 CD patients from UNITI-2 (placebo = 36, UST = 70) with biopsies were stained, of which 95 patients (90%) had sufficient samples for analysis of MV length. There were no significant differences in baseline patient characteristics between placebo- (N = 36) and UST-treated (N = 70) patients (Table 1). As a continuous variable, MV length was an effect modifier of clinical response to UST therapy (p = 0.043). The overall clinical response was significantly higher in the UST-treated group compared with placebo: 65% (40/62) vs. 39% (13/33, p = 0.03). The greatest therapeutic effect and differences were seen in the normal MV length group: clinical response UST vs. placebo, 85% (11/13) vs. 20% (1/5, p = 0.02); corresponding rates in the low MV length group were 59% (28/49) vs. 46% (12/28, p = 0.17). Similar results were seen with respect to endoscopic response: normal MV length group (75% [6/8] vs. 20% [1/5]), compared with low MV length group (65% [24/35] vs. 48% [11/23]). Conclusion: Pre-treatment ileal biopsy MV length was predictive of clinical and endoscopic response to UST in a cohort of UNITI-2 trial patients, with the greatest therapeutic effects observed in patients with normal MV length. Disclosure: Nothing to disclose. Table 1. Baseline Patient Characteristics Placebo (N = 36) Ustekinumab (N = 70) p-value Mean age, years ± SD 43 ± 14 38 ± 12 0.10 Female gender, N (%) 18 (50) 40 (57) 0.48 Ethnicity, N (%) Caucasians 32 (89) 60 (86) 0.42 African Americans 1 (3) 6 (9) Asians or others 3 (9) 4(5) Average BMI ± SD, kg/m2 26.2 ± 6.0 26.0 ± 5.8 0.46 Disease duration (Years) 6.4 [2.4, 15.9] 4.0 [1.5, 13.4] 0.15 Disease phenotype, N (%) Fistulizing 2 (6) 5 (7) 0.76 Fibrostenotic 8 (22) 14 (20) 0.18 Disease location, N (%) Ileum only 12 (33) 17 (24) 0.42 Colon only 19 (53) 34 (49) Ileum and colon 5 (14) 18(26) Prior anti-TNF exposure 14 (48 %) 27 (40%) 0.43 C-reactive protein (CRP) 2.8 [1.0, 14.4] 5.1 [2.4, 10.6] 0.55 LB04 COMBINED ILEAL BIOMARKERS CAN DISCRIMINATE RESPONDERS FROM NON-RESPONDERS TO VEDOLIZUMAB THERAPY IN CROHN’S DISEASE M.T. Osterman1, E.M. Davis2, I.O. Gordon3, K. Simpson4, M. Ciorba5, S.C. Glover6, B.P. Abraham7, E. Yee8, F. Allard8, B. Claggett9, B. Shen10, T.S. Stappenbeck4, J. Liu2 1University of Pennsylvania, Medicine, Philadelphia, United States 2University of Arkansas for Medical Sciences, Medicine, Little Rock, United States 3Cleveland Clinic Foundation, Cleveland, Pathology, Cleveland, United States 4Washington University School of Medicine, St Louis, United States 5Washington University School of Medicine, Medicine, St. Louis, United States 6University of Florida, Gainesville, United States 7Baylor College of Medicine, Houston, United States 8University of Arkansas for Medical Sciences, Pathology, Little Rock, United States 9Brigham and Women's Hospital, Little Rock, United States 10Cleveland Clinic Foundation Digestive Disease Institute, Cleveland, United States Contact E-Mail Address: jjliu@uams.edu Introduction: Several mucosal biomarkers have been identified to hold predictive values for biologic therapies in Crohn's disease (CD). Vedolizumab is an anti-integrin monoclonal antibody approved for the treatment of CD. We have recently shown that ileal epithelial cell pyroptosis, a biomarker of innate immune activation, can help identify responders to vedolizumab therapy in CD. Ileal epithelial cell microvilli length (MVL), a novel biomarker of malabsorption, was shown to be significantly reduced in CD patients and may also have predictive value for biologic treatment. The utility of using the combination of these two biomarkers to predict response to vedolizumab therapy in CD is unknown. Aims & Methods: The aim of this study was to determine the relationship between ileal epithelial cell pyroptosis and ileal MVL and whether the combination of these two biomarkers may improve the identification of responders and non-responders to vedolizumab in CD. Patients aged 18 to 80 years with known diagnosis of CD from five American IBD centers with pre-vedolizumab ileal biopsies were enrolled. Clinical response, defined as a reduction of Harvey-Bradshaw Index (HBI) of ≥5 points from pre-treatment baseline, and clinical remission, defined as HBI <5, was determined ≥6 months after therapy. Biopsy samples were sectioned and stained for pyroptosis using the Maximus Biological Assay kit (Maximus Diagnostics LLC). Ileal MVL was taken as the average of 50 measurements obtained from 10 intact villi per patient on H&E stained sections, at 100× magnification by a blinded pathologist. Clinical response rates to vedolizumab stratified by pre-treatment MVL were examined. The relationship between ileal pyroptosis and MVL was described using Spearman's correlation. The value of ileal pyroptosis and/or MVL thresholds alone or in combination for prediction of clinical response was compared using Fisher's exact test. Results: 55 CD patients with pre-treatment ileal biopsies were enrolled; 43 had adequate samples for analysis of both epithelial cell pyroptosis and MVL. The overall clinical response rate was 58% (25/43). There were no significant differences in baseline patient characteristics, disease characteristics, and concomitant medication use between responders (N = 25) and non-responders (N = 18). As a single biomarker, ileal MVL range of 1.35–1.55 µm was associated with a response rate of 82% (14/17), versus 44% (7/16) for 1.55 µm (p = 0.038). There was no significant correlation between ileal MVL with ileal epithelial cell pyroptosis (Spearman's rho = +0.11, p = 0.50). The combination criteria of ileal pyroptosis level < 14 positive cells/1000 IECs or MVL range of 1.35–1.55 µm could discern responders with response rate of 78% (21 of 27 positive for criteria) from non-responders with response rate of 25% (4 of 16 negative for criteria, p = 0.001), comparable to placebo response observed in clinical trials. Conclusion: Ileal MVL and epithelial cell pyroptosis are two independent mucosal biomarkers of clinical response to vedolizumab in CD patients. The combination of two biomarkers can discriminate responders from non-responders to vedolizumab in Crohn's disease patients. Disclosure: Elisabeth Davis and Julia Liu are patent holders of Maximus Diagnostics LLC. LB05 REAL-WORLD EXPERIENCE WITH USTEKINUMAB IN PAEDIATRIC CROHN’S DISEASE. A MULTICENTRE RETROSPECTIVE STUDY FROM PAEDIATRIC IBD PORTO GROUP OF ESPGHAN G. Pujol Muncunill1, V.M. Navas-López2, O. Ledder3, S. Cohen4, M. Lekar3, D. Turner5, K.-L. Kolho6, A. Levine7, N. Croft8, J. Bronsky9, D.S. Souval10, A. Assa11, R. Harris12, F. Kiparissi13, M. Aloi14, N. Afzal15, C. TZIVINIKOS16, J. Barrios17, C. Norden18, M.J. Balboa Vega19, S. Buderus20, A. Fernández de Valderrama21, L. de Ridder22, R. Garcia-Romero23, E. Medina24, C. Sánchez25, M. Velasco26, S. Vicente27, D.C. Wilson28, S. Naik29, O. Hradsky30, L. Cococcioni31, F.J. Martin De Carpi32; ESPGHAN IBD Porto Group 1Hospital Sant Joan de Déu, Unit for the Comprehensive Care of Paediatric Inflammatory Bowel Disease. Paediatric Gastroenterology, Hepatology and Nutrition Department, Esplugues del Llobregat, Spain 2Hospital Regional Universitario de Malaga, Malaga, Spain 3Shaare Zedek Medical Center, Jerusalem, Israel 4Tel Aviv MC, Tel Aviv, Israel 5Shaare Zedek Medical Center, Pediatric GI, Jerusalem, Israel 6University of Helsinki and Helsinki University Hospital and Tampere University and Tampere Universit, Faculty of Medicine and Biosciences, Tampere, Finland 7Wolfson Medical Center, Paediatric Gastroenterology, Holon, Israel 8The Royal London Children's Hospital, London, United Kingdom 9Faculty Hospital Motol Dept. of Pediatrics, Prague 5, Czech Republic 10Sheba Medical Center, Tel Hashomer, Israel 11Schnider Children's Medical Center, Dr., Petach Tikva, Israel 12Royal Hospital for Children, Glasgow, United Kingdom 13Great Ormond Street Hospital NHS Foundation Trust, Gastroenterology, London, United Kingdom 14Sapienza University of Rome Dept. of Pediatric Gastroenterology SIGENP IBD Group, Pediatric Gastroenterology And Liver Unit, Rome, Italy 15Southampton Children's Hospital, Southampton, United Kingdom 16Al Jalila Children's Specialty Hospital, Paediatric Gastroenterology, DUBAI, United Arab Emirates 17Hospital Universitario de Fuenlabrada, Madrid, Spain 18Hvidovre Hospital, Copenhagen, Denmark 19Hospital Virgen de la Macarena, Sevilla, Spain 20GFO-Kliniken Bonn, St. Marien-Hospital, Pediatrics, Bonn, Germany 21Hospital Universitario de Burgos, Burgos, Spain 22Erasmus MC Rotterdam Sophia Children's Hospital Dept. of Pediatric Gastroenterology, Rotterdam, Netherlands 23Hospital Universitario Miguel Servet, Zaragoza, Spain 24Hospital 12 de Octubre, Pediatrics, Madrid, Spain 25Hospital Gregorio Marañon, Madrid, Spain 26Hospital Infantil Universitario Niño Jesús, Gastroenterology, Madrid, Spain 27Hospital Universitario Ramon y Cajal, Madrid, Spain 28University of Edinburgh Child Life and Health, Paediatric Gastroenterology and Nutrition, Edinburgh,
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