758 results on '"Bruce E. Sands"'
Search Results
152. S789 Effect of Mirikizumab on Inflammatory Biomarkers in a Phase 2 Study of Patients With Crohn’s Disease
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Geert D’Haens, Stefan Schreiber, Edouard Louis, Bruce E. Sands, Elisa Gomez Valderas, Debra Miller, Noah Agada, April N. Naegeli, Paul Pollack, Jochen Schmitz, Janneke Van der Woude, Jaroslaw Kierkus, and William J. Sandborn
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Hepatology ,Gastroenterology - Published
- 2021
153. S761 Persistence of Tofacitinib Treatment in Patients With Ulcerative Colitis Who Entered the Open-Label, Long-Term Extension Study, OCTAVE OPEN Without a Clinical Response
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Remo Panaccione, Maria T. Abreu, Irina Lazariciu, Rajiv Mundayat, Nervin Lawendy, Leonardo Salese, John C. Woolcott, Bruce E. Sands, and María Chaparro
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medicine.medical_specialty ,Tofacitinib ,Hepatology ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Extension study ,Gastroenterology ,medicine.disease ,Ulcerative colitis ,Persistence (computer science) ,Tolerability ,Internal medicine ,medicine ,In patient ,Imputation (statistics) ,business - Abstract
Introduction: Drug survival in open-label, long-term extension (OLE) studies may provide information on the long-term efficacy and tolerability of a therapy. Methods: We present data on the persistence of tofacitinib treatment in the OLE study for: (1) delayed responders: induction non-responders (pts who did not achieve a clinical response [CR] after 8 weeks [wks] induction treatment with tofacitinib 10 mg BID) who achieved a CR at Wk 8 (total of 16 wks induction) of the OLE study and continued to receive 10 mg BID;(2) retreatment responders: tofacitinib 10 mg BID induction responders who experienced treatment failure with PBO in OCTAVE Sustain and entered the OLE study and received 10 mg BID, and achieved a CR at Wk 8 of the OLE study;and (3) dose escalation responders: tofacitinib 10 mg BID induction responders who experienced treatment failure with 5 mg BID in OCTAVE Sustain and entered the OLE study and received 10 mg BID, and achieved a CR at Wk 8 of the OLE study (Figure 1). The calculations are based on non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or non-responder imputation only if there are no missing data due to COVID-19. 3CDAI 50% from baseline (or for subjects with isolated ileal disease and a baseline SES-CD of 4, at least a 2-point reduction from baseline), as scored by central readers.
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- 2021
154. S786 Psychometric Evaluation of PROMIS-Fatigue Short Form Scales in Patients With Moderately to Severely Active Crohn’s Disease
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Jewel Johanns, Daphne Chan, Chenglong Han, Matthew Germinaro, Yi-Hsuan Liu, Bruce E. Sands, William J. Sandborn, Brian G. Feagan, and Yan Liu
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medicine.medical_specialty ,Crohn's disease ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,In patient ,medicine.disease ,business - Published
- 2021
155. S875 The Evolution of Clinical Trial Design in Ulcerative Colitis: Interpreting Future Endpoints Based on Post-Hoc Analyses of the Vedolizumab Phase 3 Trials GEMINI 1 and VISIBLE 1
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Rana Khan, Sharif M. Uddin, Karen Lasch, Bruce E. Sands, and William J. Sandborn
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medicine.medical_specialty ,Hepatology ,Post hoc ,business.industry ,Clinical study design ,Internal medicine ,Gastroenterology ,medicine ,business ,medicine.disease ,Ulcerative colitis ,Vedolizumab ,medicine.drug - Published
- 2021
156. S760 Persistence of Tofacitinib Treatment in Patients With Ulcerative Colitis Who Entered the Open-Label, Long-Term Extension Study, OCTAVE OPEN in Remission or With a Clinical Response
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Remo Panaccione, Maria T. Abreu, Irina Lazariciu, Rajiv Mundayat, Nervin Lawendy, Leonardo Salese, John C. Woolcott, Bruce E. Sands, and María Chaparro
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Hepatology ,Gastroenterology - Published
- 2021
157. S777 Tofacitinib for the Treatment of Ulcerative Colitis: Up to 7.8 Years of Safety Data from Global Clinical Trials
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William Sandborn, Geert D’Haens, Bruce E. Sands, Remo Panaccione, Siew C. Ng, Nervin Lawendy, Nicole Kulisek, Xiang Guo, Rajiv Mundayat, Chinyu Su, and Julian Panés
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Hepatology ,Gastroenterology - Published
- 2021
158. Factors Associated With Longitudinal Psychological and Physiological Stress in Health Care Workers During the COVID-19 Pandemic: Observational Study Using Apple Watch Data
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Katie Hyewon Choi, Lewis Tomalin, Robert Hirten, Robert Freeman, Dennis S. Charney, Bruce E. Sands, Laurie Keefer, Mayte Suárez-Fariñas, Erwin P. Bottinger, Eddye Golden, Matteo Danieletto, Anthony Biello, Claudia Calcagno, Micol Zweig, Sparshdeep Kaur, Renata Pyzik, Zahi A. Fayad, James W. Murrough, Girish N. Nadkarni, and Drew Helmus
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Adult ,Multivariate analysis ,Health Personnel ,media_common.quotation_subject ,emotion ,wearable device ,Health Informatics ,psychology ,stress ,COVID-19 Testing ,Quality of life (healthcare) ,Optimism ,Stress, Physiological ,heart rate ,Humans ,Heart rate variability ,Medicine ,observational ,app ,resilience ,Pandemics ,media_common ,Original Paper ,support ,SARS-CoV-2 ,business.industry ,nervous system ,Stressor ,heart rate variability ,COVID-19 ,Mental health ,quality of life ,health care worker ,physiology ,psychological ,Female ,New York City ,Observational study ,Psychological resilience ,business ,mental health ,Stress, Psychological ,Clinical psychology - Abstract
Background The COVID-19 pandemic has resulted in a high degree of psychological distress among health care workers (HCWs). There is a need to characterize which HCWs are at an increased risk of developing psychological effects from the pandemic. Given the differences in the response of individuals to stress, an analysis of both the perceived and physiological consequences of stressors can provide a comprehensive evaluation of its impact. Objective This study aimed to determine characteristics associated with longitudinal perceived stress in HCWs and to assess whether changes in heart rate variability (HRV), a marker of autonomic nervous system function, are associated with features protective against longitudinal stress. Methods HCWs across 7 hospitals in New York City, NY, were prospectively followed in an ongoing observational digital study using the custom Warrior Watch Study app. Participants wore an Apple Watch for the duration of the study to measure HRV throughout the follow-up period. Surveys measuring perceived stress, resilience, emotional support, quality of life, and optimism were collected at baseline and longitudinally. Results A total of 361 participants (mean age 36.8, SD 10.1 years; female: n=246, 69.3%) were enrolled. Multivariate analysis found New York City’s COVID-19 case count to be associated with increased longitudinal stress (P=.008). Baseline emotional support, quality of life, and resilience were associated with decreased longitudinal stress (P Conclusions High resilience, emotional support, and quality of life place HCWs at reduced risk of longitudinal perceived stress and have a distinct physiological stress profile. Our findings support the use of these characteristics to identify HCWs at risk of the psychological and physiological stress effects of the pandemic.
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- 2021
159. S0664 Disease Control and Changes in Individual Treatment Outcomes From Week 14 to Week 52 With Vedolizumab or Adalimumab in Ulcerative Colitis: A VARSITY Trial Post Hoc Analysis
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Richard A. Lirio, Christian Agboton, Silvio Danese, Laurent Peyrin-Biroulet, Dirk Lindner, Edward V. Loftus, Jean-Frederic Colombel, Bruce E. Sands, and Stefan Schreiber
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medicine.medical_specialty ,Hepatology ,business.industry ,Treatment outcome ,Gastroenterology ,medicine.disease ,Disease control ,Ulcerative colitis ,Vedolizumab ,Internal medicine ,Post-hoc analysis ,medicine ,Adalimumab ,business ,medicine.drug - Published
- 2020
160. S0703 Tofacitinib for the Treatment of Ulcerative Colitis: Up to 6.8 Years of Safety Data From Global Clinical Trials
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Siew C. Ng, Bruce E. Sands, Chinyu Su, Nicole Kulisek, Geert R. D'Haens, Thomas V. Jones, William J. Sandborn, Julián Panés, Nervin Lawendy, Remo Panaccione, and Rajiv Mundayat
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Clinical trial ,medicine.medical_specialty ,Tofacitinib ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,medicine.disease ,business ,Ulcerative colitis - Published
- 2020
161. S0787 An Update on the Analysis of Non-Melanoma Skin Cancer in the Tofacitinib Ulcerative Colitis Clinical Program as of May 2019
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Donna T. Judd, Julián Panés, Paulo Gustavo Kotze, Rajiv Mundayat, Nervin Lawendy, Walter Reinisch, and Bruce E. Sands
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medicine.medical_specialty ,Tofacitinib ,Hepatology ,business.industry ,Gastroenterology ,medicine ,Skin cancer ,medicine.disease ,business ,Ulcerative colitis ,Dermatology ,Non melanoma - Published
- 2020
162. S0873 Patient and Gastroenterologist Attitudes of Fecal Microbiota Transplantation as a Treatment for Inflammatory Bowel Disease
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Ari Grinspan, Bruce E. Sands, Katie A. Dunleavy, Robert Hirten, and Stephanie Stanley
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medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,Fecal bacteriotherapy ,medicine.disease ,business ,Inflammatory bowel disease - Published
- 2020
163. S0887 Fecal Calprotectin as a Surrogate Marker of Clinical Remission, Clinical Response, Endoscopic Improvement, and Histo-Endoscopic Mucosal Healing: UNIFI Induction Study
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Reena Khanna, Brian G. Feagan, Bruce E. Sands, Hongyan Zhang, and Colleen Marano
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medicine.medical_specialty ,Hepatology ,business.industry ,Surrogate endpoint ,Mucosal healing ,Internal medicine ,Gastroenterology ,Medicine ,Calprotectin ,business ,Feces - Published
- 2020
164. S0645 Efficacy and Safety of Ustekinumab for Crohn's Disease Through 5 Years: Final Results From the IM-UNITI Long-Term Extension
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Christopher Gasink, Brian G. Feagan, Omoniyi J. Adedokun, Willem J.S. de Villiers, Bruce E. Sands, Jean-Frederic Colombel, Paul Rutgeerts, Yuhua Wang, Subrata Ghosh, Stephan R. Targan, John P. Lynch, William J. Sandborn, Rory Rebuck, Bin Zou, and Stephen B. Hanauer
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Crohn's disease ,Pediatrics ,medicine.medical_specialty ,Hepatology ,business.industry ,Ustekinumab ,Gastroenterology ,medicine ,medicine.disease ,business ,medicine.drug ,Term (time) - Published
- 2020
165. S0815 Effect of Mirikizumab on Inflammatory Biomarkers in a Phase 2 Study of Patients With Crohn’s Disease
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Jochen Schmitz, William J. Sandborn, April N. Naegeli, Janneke van der Woude, Stefan Schreiber, Jaroslaw Kierkus, Geert R. D'Haens, Bruce E. Sands, Debra L. Miller, Edouard Louis, Paul F. Pollack, Noah Agada, and Elisa Gomez Valderas
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medicine.medical_specialty ,Crohn's disease ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,Phases of clinical research ,business ,medicine.disease ,Inflammatory biomarkers - Published
- 2020
166. S0766 An Interdisciplinary IBD Center Improves Adherence to Care in IBD Patients With Medicaid
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Robert Hirten, Rohini Bahethi, Ryan C. Ungaro, Bruce E. Sands, Benjamin L. Cohen, Zachary A. Borman, Anam Rivzi, Haley M. Zylberberg, Christina Wang, Sally Engelman, and Ricardo Yanes
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medicine.medical_specialty ,Hepatology ,business.industry ,Family medicine ,Gastroenterology ,Medicine ,Center (algebra and category theory) ,business ,Medicaid - Published
- 2020
167. 611 THE REAL-WORLD EFFECTIVENESS OF USTEKINUMAB IN THE TREATMENT OF CROHN'S DISEASE
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J Izanec, Monika Fischer, Corey A. Siegel, Matthew Bohm, Stephanie Gold, Garrett Lawlor, Brendan P. Halloran, Elliot Coburn, Waseem Ahmed, Rajat Garg, Parambir S. Dulai, Ellen Scherl, Edward V. Loftus, Nabeeha Mohy-ud-din, David Hudesman, Jean-Frederic Colombel, Arun Swaminath, Daniel C. Baumgart, Amanda M. Johnson, Ryan C. Ungaro, Danah Mohammad, Vipul Jairath, Miguel Regueiro, Maria Barsky, Sagi Sashi, Hannah Todorowski, Manik Aggarwal, Gursimran Kochhar, Benjamin H. Click, Thomas A. Ullman, Samantha Zullow, Christopher Gasink, David H. Bruining, Sunanda V. Kane, Manasi Agrawal, Amanda M. Teeple, Zhijie Ding, Jonathan S. Galati, Brigid S. Boland, Komal Lakhani, Neeraj Narula, Bruce E. Sands, Daniel F. Hogan, Farhad Peerani, William J. Sandborn, Erik Muser, Shannon Chang, Anita Afzali, Siddharth Singh, Samit Datta, ThucNhi T. Dang, and Dana J. Lukin
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Crohn's disease ,medicine.medical_specialty ,Hepatology ,business.industry ,Ustekinumab ,Gastroenterology ,medicine ,business ,medicine.disease ,Dermatology ,medicine.drug - Published
- 2021
168. 129 SAFETY OF USTEKINUMAB IN IBD: POOLED SAFETY ANALYSIS THROUGH 5 YEARS IN CD AND 2 YEARS IN UC
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Christopher Gasink, Silvio Danese, Colleen Marano, Bruce E. Sands, Brian G. Feagan, Elyssa Ott, Ye Miao, Ilia Tikhonov, John P. Lynch, Subrata Ghosh, and William J. Sandborn
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medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Ustekinumab ,Gastroenterology ,medicine ,business ,medicine.drug - Published
- 2021
169. P271 Evolving Targets in Ulcerative colitis: Defining Disease Clearance in the VARSITY Study
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Dirk Lindner, Richard A. Lirio, Edward V. Loftus, Stefan Schreiber, Bruce E. Sands, Silvio Danese, L Peyrin-Biroulet, J.-F. Colombel, and Christian Agboton
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business.industry ,ADRENAL CORTICOSTEROIDS ,Gastroenterology ,Composite outcomes ,General Medicine ,Disease ,Treatment goals ,medicine.disease ,Ulcerative colitis ,Treatment failure ,Vedolizumab ,Immunology ,medicine ,Adalimumab ,business ,medicine.drug - Abstract
Background In VARSITY, the first head-to-head randomized controlled trial of biologics, vedolizumab (VDZ) was superior vs adalimumab (ADA) in achieving clinical remission (CR) at Week 52 in patients (pts) with moderate to severe ulcerative colitis (UC).1 Current treatment goals in UC are based on clinical symptoms and endoscopy, with histologic improvement considered an aspirational goal.2-4 In pts with CR in VARSITY, greater treatment differences between VDZ and ADA at Week 52 were seen in endoscopic improvement and histologic response. Here, data from VARSITY were used to define disease clearance: a novel composite outcome in UC comprising clinical and endoscopic remission plus minimal histologic disease activity. Methods VARSITY was a phase 3b, randomized, double-blind, double-dummy, active-control trial of treatment with VDZ (300mg IV Q8W) vs ADA (40mg SC Q2W) maintenance after induction. Pts were randomized in a treat through design, and no dose escalation was allowed. For these analyses, based on pts who completed the study until Week 52, disease clearance was defined as a composite outcome based on 1) CR: partial Mayo score ≤2 and no individual subscore >1 (excluding sigmoidoscopy subscore); 2) endoscopic improvement: endoscopic subscore ≤1; and 3) absence of active histologic disease (minimum histological disease activity [MHDA]): Robarts Histology Index (RHI) 100 µg/g. Results More pts in the VDZ treatment group than the ADA group achieved disease clearance at Week 52 (VDZ: 112/383, 29.2%, 95% CI 24.7-34.1 vs ADA: 63/386, 16.3%, 95% CI 12.8-20.4). Compared with treatment failures (VDZ: 92/383, 24.0% vs ADA: 134/386, 34.7%, Table 1), disease clearers had lower C-reactive protein (CRP) baseline mean values (7.4mg/L and 6.4mg/L vs 13.6mg/L and 9.4mg/L for disease clearers vs treatment failures, for VDZ and ADA, respectively). Fewer pts with inflammatory burden at baseline (CRP ≥5 mg/L and fecal calprotectin >100 µg/g) achieved disease clearance (Fig 1). Baseline corticosteroid use was more frequent in ADA disease clearers (42.9%) compared with VDZ disease clearers (32.1%). Conclusion Disease clearance is a novel and achievable composite outcome that is achieved by almost one third of pts in the VDZ treatment group in VARSITY. Analyses are ongoing to further characterize the trajectory leading to disease clearance as well as the role of baseline characteristics.
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- 2021
170. 225 PROGNOSTIC VALUE OF FECAL CALPROTECTIN IN BIOLOGIC-TREATED PATIENTS WITH ULCERATIVE COLITIS
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Richard A. Lirio, Karen Lasch, Jingjing Chen, Brian G. Feagan, Parambir S. Dulai, and Bruce E. Sands
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medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,Medicine ,Calprotectin ,business ,medicine.disease ,Value (mathematics) ,Ulcerative colitis ,Feces - Published
- 2021
171. Sa567 A COMPREHENSIVE INTERDISCIPLINARY CARE PROGRAM FOR RECENTLY DIAGNOSED INFLAMMATORY BOWEL DISEASE PATIENTS IS ASSOCIATED WITH LOWER HEALTHCARE RESOURCE UTILIZATION
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Kristina Matos, Alexis Sherman, Stephanie Stanley, Anabella Castillo, Stacy Tse, Ryan C. Ungaro, Amanda Hyne, Loren Rabinowitz, Stephanie Gold, Marla Dubinsky, William J. Rivera Carrero, Laurie Keefer, Bruce E. Sands, Ari Grinspan, Laura Manning, and Jean-Frederic Colombel
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medicine.medical_specialty ,Hepatology ,business.industry ,Health care ,Gastroenterology ,medicine ,business ,Intensive care medicine ,Care program ,medicine.disease ,Inflammatory bowel disease ,Resource utilization - Published
- 2021
172. Sa463 VARIATIONS IN BASELINE DISEASE CHARACTERISTICS OF PATIENTS WITH ACTIVE, MODERATE TO SEVERE CROHN'S DISEASE, BY DISEASE LOCATION
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Mirko Sikirica, Chenglong Han, Yan Liu, Brian G. Feagan, William J. Sandborn, Mei-lun Wang, Bin Zou, Yi-Hsuan Liu, Bruce E. Sands, and Christopher Gasink
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Moderate to severe ,medicine.medical_specialty ,Crohn's disease ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,Medicine ,Disease characteristics ,Disease ,business ,Baseline (configuration management) ,medicine.disease - Published
- 2021
173. Adverse events of special interest in clinical trials of rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and psoriasis with 37 066 patient-years of tofacitinib exposure
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Ann Madsen, Thomas V. Jones, Stanley Cohen, Huaming Tan, Kim A. Papp, Hernan Valdez, Bruce E. Sands, Lori Stockert, Gerd R Burmester, and Peter Nash
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medicine.medical_specialty ,rheumatoid ,Immunology ,Arthritis ,Arthritis, Rheumatoid ,Psoriatic arthritis ,Piperidines ,Rheumatology ,Internal medicine ,Psoriasis ,therapeutics ,medicine ,Humans ,Immunology and Allergy ,autoimmune diseases ,Adverse effect ,Tofacitinib ,business.industry ,Arthritis, Psoriatic ,Treatments ,medicine.disease ,Ulcerative colitis ,Clinical trial ,Pyrimidines ,Treatment Outcome ,arthritis ,Rheumatoid arthritis ,Medicine ,Colitis, Ulcerative ,psoriatic ,business - Abstract
ObjectivesTo analyse adverse events (AEs) of special interest across tofacitinib clinical programmes in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ulcerative colitis (UC) and psoriasis (PsO), and to determine whether the incidence rates (IRs; unique patients with events per 100 patient-years) of these events are consistent across diseases.MethodsThe analysis included data from patients exposed to ≥1 dose of tofacitinib in phase 1, 2, 3 or 3b/4 clinical trials and long-term extension (LTE) studies (38 trials) in RA (23 trials), PsA (3 trials), UC (5 trials) and PsO (7 trials). All studies were completed by or before July 2019, except for one ongoing UC LTE study (data cut-off May 2019). IRs were obtained for AEs of special interest.Results13 567 patients were included in the analysis (RA: n=7964; PsA: n=783; UC: n=1157; PsO: n=3663), representing 37 066 patient-years of exposure. Maximum duration of exposure was 10.5 years (RA). AEs within the ‘infections and infestations’ System Organ Class were the most common in all diseases. Among AEs of special interest, IRs were highest for herpes zoster (non-serious and serious; 3.6, 1.8, 3.5 and 2.4 for RA, PsA, UC and PsO, respectively) and serious infections (2.5, 1.2, 1.7 and 1.3 for RA, PsA, UC and PsO, respectively). Age-adjusted and sex-adjusted mortality ratios (weighted for country) were ≤0.2 across cohorts.ConclusionsThe tofacitinib safety profile in this analysis was generally consistent across diseases and with longer term follow-up compared with previous analyses.
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- 2021
174. 132 EFFICACY AND SAFETY OF MIRIKIZUMAB AFTER 52-WEEKS MAINTENANCE TREATMENT IN PATIENTS WITH MODERATE-TO-SEVERE CROHN'S DISEASE
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Vipin Arora, Toshifumi Hibi, Debra L. Miller, Geert R. D'Haens, Paul F. Pollack, Fumihito Hirai, Elisa Gomez Valderas, Bruce E. Sands, April N. Naegeli, Laurent Peyrin-Biroulet, Vipul Jairath, Jay Tuttle, Ruth Belin, William J. Sandborn, Peter D.R. Higgins, and Maria T. Abreu
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Moderate to severe ,Crohn's disease ,medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,In patient ,medicine.disease ,business - Published
- 2021
175. Sa650 DIGITAL NAVIGATION FOR COLONOSCOPY: AN AUTOMATED INTERVENTION TO DECREASE COLONOSCOPY NO-SHOWS
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Shashank Garg, Farah Fasihuddin, Ashish Atreja, Jason Rogers, Lina Jandorf, Raveena Kelkar, Parth D. Trivedi, Deep Mehta, Sarthak Kakkar, Eric Geng, David A. Greenwald, and Bruce E. Sands
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medicine.medical_specialty ,Hepatology ,medicine.diagnostic_test ,business.industry ,Intervention (counseling) ,General surgery ,Gastroenterology ,Medicine ,Colonoscopy ,business - Published
- 2021
176. Su461 SHORTER DISEASE DURATION IN PATIENTS WITH CROHN'S DISEASE IS ASSOCIATED WITH HIGHER RATES OF REMISSION WITH USTEKINUMAB
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Monika Fischer, Erik Muser, Arun Swaminath, Rajat Garg, Ryan C. Ungaro, Corey A. Siegel, Farhad Peerani, Dana J. Lukin, Manik Aggarwal, Thomas A. Ullman, Samantha Zullow, Christopher Gasink, William J. Sandborn, Waseem Ahmed, Anita Afzali, J Izanec, Matthew Bohm, Brendan P. Halloran, Amanda M. Johnson, Zhijie Ding, Benjamin H. Click, Gursimran Kochhar, David Hudesman, Vipul Jairath, Miguel Regueiro, Ellen Scherl, Nabeeha Mohy-ud-din, Siddharth Singh, Edward V. Loftus, Samit Datta, ThucNhi T. Dang, Sunanda V. Kane, Shannon Chang, Danah Mohammad, Parambir S. Dulai, Jonathan S. Galati, Maria Barsky, Sagi Sashi, Stephanie Gold, Jean-Frederic Colombel, Brigid S. Boland, Elliot Coburn, Daniel C. Baumgart, Manasi Agrawal, Hannah Todorowski, Amanda M. Teeple, Bruce E. Sands, Komal Lakhani, Daniel F. Hogan, Neeraj Narula, David H. Bruining, and Garrett Lawlor
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medicine.medical_specialty ,Crohn's disease ,Hepatology ,business.industry ,Disease duration ,Gastroenterology ,medicine.disease ,Internal medicine ,Ustekinumab ,medicine ,In patient ,business ,medicine.drug - Published
- 2021
177. Fr549 IMPACT OF MULTI-DISCIPLINARY IBD SPECIALTY CLINIC CARE ON OUTCOMES IN IBD PATIENTS INSURED BY MEDICAID
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Sally Engelman, Ricardo Yanes, Robert Hirten, Bhavana Bhagya Rao, Christina Wang, Zachary A. Borman, Haley M. Zylberberg, Ryan C. Ungaro, Bruce E. Sands, and Benjamin L. Cohen
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medicine.medical_specialty ,Hepatology ,Multi disciplinary ,business.industry ,Family medicine ,Gastroenterology ,Specialty ,Medicine ,business ,Medicaid - Published
- 2021
178. Fr540 THE PHARMACOKINETICS AND IMMUNOGENICITY OF 5 YEARS OF TREATMENT WITH USTEKINUMAB: RESULTS FROM THE IM-UNITI LONG-TERM EXTENSION
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Brian G. Feagan, Yuhua Wang, Christopher Gasink, Omoniyi J. Adedokun, Bruce E. Sands, Subrata Ghosh, Willem J.S. de Villiers, John P. Lynch, Bin Zou, and William J. Sandborn
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Oncology ,medicine.medical_specialty ,Hepatology ,Pharmacokinetics ,business.industry ,Internal medicine ,Immunogenicity ,Ustekinumab ,Gastroenterology ,medicine ,business ,medicine.drug ,Term (time) - Published
- 2021
179. Eldelumab [anti-interferon-γ-inducible protein-10 antibody] Induction Therapy for Active Crohn’s Disease: a Randomised, Double-blind, Placebo-controlled Phase IIa Study
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Bruce E. Sands, Paul Rutgeerts, Robert Petryka, Pranab Mitra, Allison Luo, Jean-Frederic Colombel, Subrata Ghosh, and William J. Sandborn
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Randomization ,Eldelumab ,Placebo ,Severity of Illness Index ,Gastroenterology ,Inflammatory bowel disease ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Double-Blind Method ,Gastrointestinal Agents ,Internal medicine ,medicine ,Humans ,Adverse effect ,Gastrointestinal agent ,Crohn's disease ,Dose-Response Relationship, Drug ,business.industry ,Remission Induction ,Antibodies, Monoclonal ,Colonoscopy ,General Medicine ,Middle Aged ,medicine.disease ,Crohn's Disease Activity Index ,030104 developmental biology ,Female ,030211 gastroenterology & hepatology ,business - Abstract
This 11-week Phase IIa induction study evaluated the efficacy and safety of eldelumab in patients with active Crohn's disease.Adults with Crohn's Disease Activity Index 220-450 were randomised 1:1:1 to placebo or eldelumab 10 or 20 mg/kg intravenously on Days 1 and 8, and alternate weeks thereafter. All patients underwent ileocolonoscopy at baseline. Patients with active inflammation according to the Simplified Endoscopic Score for Crohn's Disease criteria [the originally planned endoscopy cohort] underwent another ileocolonoscopy at Week 11 at the investigator's discretion. All ileocolonoscopies were centrally read. The primary objective was identification of the eldelumab target exposure for induction of remission [absolute Crohn's Disease Activity Index score150]. Rates of clinical response [reduction of ≥ 100 from baseline or absolute score150 Crohn's Disease Activity Index], remission, and endoscopic improvements were also assessed.A total of 121 patients were randomised. The eldelumab exposure-remission relationship was not significant at Week 11. Numerically higher remission and response rates were reported with eldelumab 20 mg/kg [29.3% and 41.5%, respectively] and 10 mg/kg [22.5% and 47.5%] versus placebo [20.0% and 35.0%]. A higher proportion of patients with a baseline Simplified Endoscopic Score for Crohn's Disease2 who received eldelumab achieved a 50% improvement in score and greater reductions from baseline endoscopy scores overall versus placebo. Adverse events were comparable across treatment groups.No exposure-remission relationship was seen with eldelumab. Eldelumab induction treatment demonstrated trends towards clinical and endoscopic efficacy. Safety was consistent with that reported previously. ClinicalTrials.gov identifier: NCT01466374.
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- 2017
180. Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials
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Bruce E. Sands, Julián Panés, Gary Chan, Paul J. Healey, Stefan Schreiber, Michele Moscariello, Peter D.R. Higgins, Geert R. D'Haens, Amy Marren, Wojciech Niezychowski, Wenjin Wang, Brian G. Feagan, Severine Vermeire, E Maller, Jean-Frederic Colombel, William J. Sandborn, Remo Panaccione, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Gastroenterology and Hepatology
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,CROHN'S DISEASE ,Pharmacology ,Placebo ,Severity of Illness Index ,IMMUNOLOGY ,Maintenance Chemotherapy ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Double-Blind Method ,Piperidines ,Maintenance therapy ,Internal medicine ,Severity of illness ,medicine ,Humans ,Pyrroles ,Protein Kinase Inhibitors ,Janus kinase inhibitor ,Tofacitinib ,biology ,business.industry ,Remission Induction ,Inflammatory Bowel Disease ,C-reactive protein ,Gastroenterology ,Middle Aged ,Infliximab ,Clinical trial ,C-Reactive Protein ,Pyrimidines ,030104 developmental biology ,biology.protein ,Female ,030211 gastroenterology & hepatology ,business ,CLINICAL TRIALS ,medicine.drug - Abstract
Objective Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). Design We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study. Results 180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (p
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- 2017
181. Investigator-Initiated IBD Trials in the United States
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Kristen Anton, Anastasia Ivanova, James D. Lewis, Barbara Schliebe, Bruce E. Sands, Robert S. Sandler, Mark T. Osterman, Christopher Martin, Hans H Herfarth, Millie D. Long, Peter D.R. Higgins, Kim L. Isaacs, and Susan A. Jackson
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Protocol (science) ,medicine.medical_specialty ,Medical education ,Gastroenterology ,MEDLINE ,Inflammatory Bowel Diseases ,law.invention ,Patient recruitment ,03 medical and health sciences ,0302 clinical medicine ,Clinical research ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Data quality ,Physical therapy ,medicine ,Immunology and Allergy ,030211 gastroenterology & hepatology ,In patient ,Psychology - Abstract
Investigator-initiated randomized clinical trials are the backbone of academic clinical research. Investigator-initiated trials (IITs) complement the large clinical studies sponsored by industry and address questions, which are usually not the main focus of a commercially directed research but have the purpose to confirm, improve, or refute clinically important questions with regard to diagnostic and therapeutic approaches in patient care. The aim of this review is to illustrate the necessary steps to start and complete an IIT in the field of inflammatory bowel diseases in the United States. The initial milestones for an investigator include structuring a protocol, planning and building of the trial infrastructure, accurately estimating the costs of the trial, and gauging the time span for recruitment. Once the trial has begun it is important to keep patient recruitment on target, monitor of the data quality, and document treatment emergent adverse events. This article provides a framework for the different phases of an IIT and outlines potential hurdles, which could hinder a successful execution.
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- 2017
182. DOP65 Mirikizumab regulates genes involved in anti-TNF resistance and ulcerative colitis disease activity
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B Jia, Bruce E. Sands, Klaus Gottlieb, Jochen Schmitz, Richard E. Higgs, Boyd Steere, Venkatesh Krishnan, Nick Powell, Yushi Liu, Jay Tuttle, and W J Sandborn
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biology ,business.industry ,Gastroenterology ,Interleukin ,General Medicine ,medicine.disease ,Ulcerative colitis ,Stromelysin 1 ,Immunology ,Gene expression ,Interleukin 23 ,biology.protein ,Medicine ,Tumor necrosis factor alpha ,Antibody ,business ,Gene - Abstract
Background Mirikizumab (miri), a p19-directed IL-23 antibody, demonstrated efficacy and was well-tolerated in a phase 2 randomised clinical trial in patients with moderate-to-severe UC (NCT02589665). This abstract explores gene expression changes in colonic tissue from study patients and their association with clinical outcomes. Methods Patients were randomised 1:1:1:1 to receive intravenous placebo (PBO, N = 63), miri 50 mg (N = 63) or 200 mg (N = 62) with the possibility of exposure-based dose increases, or fixed miri 600 mg (N = 61) every 4 weeks for 12 weeks. Patient biopsies were collected at baseline (BL) and Week 12, and differential gene expression was measured using an Affymetrix HTA2.0 exon-format microarray workflow. Genes were represented by their largest groups of highly correlated exons. Weeks 0 and 12 data were compared in all treatment groups to produce differential expression values (DEVs). Mean fold changes in DEVs between PBO and each dose group were calculated in a mixed-effect model. A threshold of false discovery rate-adjusted p-value ≤ 0.05 was applied to the significance of the fold change values, and a filter of an absolute value for the fold changes of ≥0.5 log2 units was applied. Results The greatest improvement in clinical outcomes at Week 12 was observed in the 200 mg miri group1; likewise, the greatest PBO-adjusted change from BL in transcripts was observed in this group. Transcripts correlating with key UC disease activity indices at BL, including modified Mayo score (MMS), ulcerative colitis Endoscopic Index of Severity (UCEIS), Geboes score, and Robarts Histopathology Index (RHI), included MMP1, MMP3, S100A8, IL1B, and UGT2A3, with the highest correlations occurring with the histopathologic indices (Figure 1). Miri treatment modulated the expression of transcriptional modules predicted to be enriched in cell profiles identified as key drivers of UC2 (Table 1, columns 1–2) as well as genes determined to be associated with UC by genome-wide association studies (GWAS; Table 1, column 3). Moreover, miri treatment affected transcripts involved in resistance to anti-TNF treatments (Table 1, column 4). A number of the genes in these categories were among those most affected by miri treatment (Table 1, columns 5–6). Conclusion This is the first large-scale gene expression study of diseased tissue from UC patients treated with anti-IL23p19 therapy. It is the first study to show how anti-IL23p19 therapy modulates biological pathways involved in resistance to anti-TNFs. These results are consistent with the demonstrated efficacy of miri in patients in whom TNF antagonists have failed. References
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- 2020
183. P633 Sustained reduction of IL-23-related cytokines IL-17A and IL-22 in a phase 2 study of mirikizumab in the treatment of patients with moderately-to-severely active ulcerative colitis through week 52
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Jochen Schmitz, Stephen Ho, Sean E. Sissons, Taku Kobayashi, Richard E. Higgs, W J Sandborn, Jay Tuttle, Bruce E. Sands, and G R D’Haens
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biology ,business.industry ,medicine.medical_treatment ,Gastroenterology ,Phases of clinical research ,Interleukin ,General Medicine ,medicine.disease ,Ulcerative colitis ,Interleukin 22 ,Cytokine ,Immunology ,Interleukin 23 ,biology.protein ,Medicine ,Interleukin 17 ,Antibody ,business - Abstract
Introduction Interleukin (IL)-23 is a cytokine involved in the pathogenesis of ulcerative colitis (UC). Mirikizumab (miri) is a p19-directed IL-23 antibody that demonstrated efficacy and was well-tolerated in patients with moderate-to-severely active UC during 52 weeks (weeks) of a Phase 2 randomised clinical trial (AMAC, NCT02589665). Exploration of IL-23 pathway biomarkers supports an understanding of drug activity and mechanism of action. These analyses describe exploratory biomarker results in plasma for IL-23 pathway cytokines, IL-22 and IL-17A, in subjects that responded to miri induction treatment and continued with maintenance treatment up to Week 52. Methods Patients with moderately-to-severely active UC (Mayo score 6–12 with a minimum endoscopic subscore [ES] ≥2) were randomised 1:1:1:1 to receive intravenous placebo (pbo) (N=63), miri 50mg (N=63) or 200mg (N=62) with possibility of exposure-based (EB) increases, or fixed miri 600mg (N=61) every 4 weeks, with efficacy assessment at Week 12. Miri-treated patients who achieved a clinical response at Week 12 were re-randomised 1:1 into a double-blind maintenance period to receive miri 200mg subcutaneously every 4 weeks (Q4W; N=47) or every 12 weeks (Q12W; N=46), and were treated through Week 52. Plasma EDTA samples were collected at Weeks 0, 4, 12, 24, and week 52 to evaluate circulating levels of IL-17A and IL-22. Results Baseline (BL) characteristics of patients who entered the maintenance period were similar between groups. At BL, 52.7% had previously received a biologic. At Week 52, 46.8% of patients in the Q4W group and 37.0% in the Q12W group were in clinical remission. Initial reductions in median IL-17A and IL-22 plasma concentrations during the induction phase were observed in the combined miri re-randomised treated groups (50 mg, 200 mg, 600 mg to either 200 mg Q4W, or Q12W) with −86.2/−59.0 % change from BL to Week 12 in the 200 mg Q4W group and −141.1/−55.8 % change from BL in the 200mg Q12W group (Figure). At Week 52, further numerical reductions from Week 12 in IL-17A and IL-22 levels were observed with −74.4/−32.1% change from Week 12 in the 200 mg Q4W group and −69.8%/−47.7% change from Week 12 in the 200 mg Q12W group. Conclusion Patients treated with maintenance mirikizumab had further reductions in plasma levels of the IL-23-dependent pro-inflammatory cytokines, IL-17A and IL-22, beyond that initially observed in the induction phase. These data suggest sustained biologic activity of mirikizumab in patients with moderately-to-severely active UC during maintenance. Treatment with mirikizumab for 52 weeks leads to normal, or near normal (as observed in healthy volunteer plasma) circulating levels of IL-17A and IL-22.
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- 2020
184. P428 Oral mesalamine use in Crohn’s disease after implementation of the American College of Gastroenterology guidelines: a TARGET-IBD cohort study
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M Weiss, Mph Millie D. Long Md, David T. Rubin, Stephanie Watkins, J Hanson, Nitin Gupta, Faten Aberra, Marla Dubinsky, Derek Gazis, Bruce E. Sands, and Miguel Regueiro
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Crohn's disease ,medicine.medical_specialty ,business.industry ,Gastroenterology ,General Medicine ,medicine.disease ,Inflammatory bowel disease ,Drug usage ,Internal medicine ,medicine ,business ,Irritable bowel syndrome ,Cohort study - Abstract
Background American College of Gastroenterology (ACG) guidelines for the management of adults with Crohn’s disease (CD) in March 2018 state that oral mesalamine, ‘should not be used…to treat CD.’ 1 This abstract estimates the prevalence of any use of mesalamine among patients with CD before and after the implementation of the guideline. It also aims to describe current utilisation patterns of mesalamine in CD by disease phenotype, location, and concomitant use of biologic agents. Methods TARGET-IBD is a longitudinal cohort of IBD patients receiving usual care in the USA; this abstract includes CD patients enrolled between March 2017 and December 2018. Medication use was captured as any use in the follow-up period. Use of mesalamine was stratified into patients who were on mesalamine alone or patients on mesalamine and a biologic. The proportion of patients on mesalamine was estimated in time windows after the policy change to discern penetration into usual practice. Results 732 patients from TARGET-IBD who had baseline data prior to the new recommendation were included. Of these, 14% used mesalamine only, 8% used mesalamine plus a biologic, and 78% did not use mesalamine. A total of 65% received care in academic centres and the median duration of disease at enrolment was 12 years. The distribution of patient characteristics was similar after the policy change. Six months after the ACG recommendation, 11% of patients used mesalamine only, 7% of patients were on mesalamine plus a biologic, and 82% did not use mesalamine. Prevalence of use for the 3 and 6 month time windows was similar. Subsequent therapy changes and additions in patients on mesalamine are shown in Figure 1. Location (colon vs. ileum) and type of CD (inflammatory vs. fistulising) were statistically significant predictors of the odds of any mesalamine use both before and after the policy change (OR 3.233 (CI 1.725–6.061) and 3.334 (CI 1.931–5.755, respectively)). Conclusion Mesalamine use remained stable in the TARGET-IBD CD population, despite the release of the ACG guideline. Individuals with colonic, inflammatory disease were more likely to receive mesalamine, as were Medicare recipients. There was little difference between academic and community practice in implementation of the new standards. Given that the guidelines are relatively new, it is important to follow these participants over a longer period and monitor practice differences and ways to reinforce the practice recommendations to improve the quality and cost of care.
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- 2020
185. P682 Faecal calprotectin and C-reactive protein levels are associated with long-term clinical and endoscopic outcomes: Analysis of the OASIS open-label extension trial of etrasimod for ulcerative colitis
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Michael Chiorean, Severine Vermeire, Bruce E. Sands, Jinkun Zhang, Andres Yarur, Walter Reinisch, Julià Panés, Snehal Naik, Christopher H Cabell, Laurent Peyrin-Biroulet, and W J Sandborn
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medicine.medical_specialty ,Intention-to-treat analysis ,Randomization ,biology ,Surrogate endpoint ,business.industry ,C-reactive protein ,Gastroenterology ,Outcome analysis ,General Medicine ,medicine.disease ,Faecal calprotectin ,Ulcerative colitis ,Internal medicine ,medicine ,biology.protein ,Open label ,business - Abstract
Background Reliable biomarkers of ulcerative colitis (UC) disease activity may be useful in clinical trials and practice. Etrasimod is an oral, selective, sphingosine 1-phosphate receptor modulator with efficacy in a 12-week, phase 2, double-blind (DB), randomised, controlled trial in adult patients with moderately-to-severely active UC (OASIS; NCT02447302). Patients who completed the DB study were eligible to enrol in an open-label extension (OLE; NCT02536404) and receive etrasimod 2 mg once daily for up to an additional 34 weeks. The aim of this post-hoc analysis was to assess the correlation of sequential faecal calprotectin (FC) and C-reactive protein (CRP) levels throughout the DB study and OLE with clinical and endoscopic outcomes at end of treatment (EOT) in the OLE. Methods In the DB study, patients received etrasimod 1 mg, etrasimod 2 mg or placebo. The OLE evaluable cohort comprised patients who received etrasimod 2 mg throughout the OLE. The modified intention-to-treat (mITT) population comprised patients with non-missing assessments. EOT was the last observation for each patient, occurring at week 46 (OLE week 34) for study completers or at last visit for patients who discontinued or had missing data. Endpoints were modified Mayo Clinic score (mMCS; range 0–9; including endoscopy, rectal bleeding [RB], and stool frequency [SF]); clinical remission (endoscopic subscore ≤1 [with absence of friability], RB ≤1, and SF score ≤1 with ≥1 point decrease from DB baseline); clinical response (clinical remission or decrease in mMCS of ≥2 points and ≥30% decrease from DB baseline, with either a RB decrease of ≥1 or RB score of ≤1); and endoscopic improvement (subscore ≤1). FC and CRP were measured longitudinally to EOT. Comparisons between subgroups were assessed with a Wilcoxon rank-sum test (2-sided P values). Analysis of correlation between variables was conducted using the Spearman’s rank coefficient. Results The evaluable cohort included 105 patients, 31 of whom received etrasimod 2 mg throughout both DB and OLE periods. At EOT 70%, 35% and 45% of patients in the mITT evaluable cohort had clinical response, clinical remission and endoscopic improvement, respectively. Differences in FC and CRP levels between patients with and without clinical remission at EOT are shown in Figures 1 and 2, respectively for patients who received etrasimod 2 mg throughout both the DB and OLE periods. Correlation analyses of FC and CRP with clinical (mMCS) and endoscopic disease activity and with each other are shown in Table 1. Conclusion FC and CRP appear to correlate with clinical and endoscopic outcomes over long-term treatment with etrasimod. Additional validation is needed to determine their utility in treat-to-target management strategies.
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- 2020
186. P565 Efficacy and safety of long-term treatment with ustekinumab in moderate–severe ulcerative colitis patients with delayed response to ustekinumab induction: Results from UNIFI 2-year long-term extension
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Maria T. Abreu, Silvio Danese, Colleen Marano, Ramesh P. Arasaradnam, L Peyrin-Biroulet, Unifi Investigators, Bruce E. Sands, Ellen Scherl, Jewel Johanns, David Rowbotham, Hongyan Zhang, Yiying Zhou, Christopher D. O'Brien, Tadakazu Hisamatsu, and Rupert W. Leong
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medicine.medical_specialty ,Delayed response ,Randomization ,Long term treatment ,business.industry ,ADRENAL CORTICOSTEROIDS ,Gastroenterology ,General Medicine ,medicine.disease ,Ulcerative colitis ,Vedolizumab ,Term (time) ,Internal medicine ,Ustekinumab ,medicine ,business ,medicine.drug - Abstract
Background Ustekinumab (UST) has been shown to induce and maintain clinical response and remission in moderate–severe UC patients in the UNIFI study. In the UNIFI maintenance study, the primary randomised population consisted of patients who were in clinical response 8weeks after UST induction treatment. Patients who had a delayed response to induction were also eligible for the maintenance study but were not included in the randomised analysis set. Here, we present the efficacy and safety of UST maintenance among delayed responders who were treated in the UNIFI long-term extension(LTE). Methods UNIFI was a single protocol of induction and randomised withdrawal maintenance studies in patients with moderate–severe UC who failed conventional or biologic therapy(including TNF antagonists and/or vedolizumab). Delayed responders were patients who were not in clinical response to UST IV induction at Week8 but achieved response at Week16 following a single UST90mg SC dose at Week8. These patients entered the maintenance study and continued to receive UST90mg SC q8w. Patients who completed Week44 evaluations were eligible to enter LTE continuing to receive UST90mg SC q8w. Efficacy in delayed responders to UST(who were treated in LTE) was evaluated over time through Week92 and safety through Week96. Results 116 delayed responders to UST induction were treated in the LTE, including 58 who had previously failed biologic therapy and 58 who had not failed biologic therapy, 54 of whom were bio-naïve. Symptomatic remission(defined as stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0) rates in delayed responders to UST induction increased from maintenance baseline to Weeks 44 and 92 (Table 1). Similar trends were seen within the biologic failure subgroups; although, rates among patients who had not failed biologics (primarily bio-naïve) were greater than those of patients who had failed biologics. Among the 79.3% (n = 92/116) of delayed responders to UST in symptomatic remission at Week 92, 94.6% (n = 87/92) were corticosteroid free. Safety data for randomised and non-randomised patients treated in UNIFI LTE is in Table2. The safety profile for UST in delayed responders was generally similar to that observed among patients randomised to UST; no new safety signals were observed. Conclusion Delayed responders to UST treatment maintained symptomatic remission through Week 92 with UST90mg SC q8w and the majority did so in the absence of corticosteroids.
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- 2020
187. P621 Physician preferences for biologics (originator vs. biosimilar) for the treatment of ulcerative colitis in France, Germany and the UK
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Bruce E. Sands, A Lax, Mei Sheng Duh, Lynn Huynh, H Sipsma, S Hass, Arpita Nag, and Mu Cheng
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medicine.medical_specialty ,business.industry ,Gastroenterology ,Biosimilar ,General Medicine ,Interim analysis ,medicine.disease ,Ulcerative colitis ,Infliximab ,Vedolizumab ,Anti-Tumor Necrosis Factor Therapy ,Biosimilar Pharmaceuticals ,Internal medicine ,medicine ,Adalimumab ,business ,medicine.drug - Abstract
Background Although originator biologics are effective therapies for patients with ulcerative colitis (UC), they can be costly and may not be widely available. Therefore, less expensive biosimilars have been developed and approved to treat and manage symptoms. In this new treatment landscape, UC-treatment preferences are unknown. Thus, this interim analysis aimed to characterise physician preferences for biologics for the treatment of UC in France, Germany and the UK. Methods As part of a broader chart review study, treatment preferences were also collected from participating gastroenterologists and general practitioners (GPs) in France, Germany and the UK who had treated patients (≥ 18 years) with moderate-to-severe UC who had received ≥ 1 UC-related biologic any time from 2014 to 25 October 2019. Descriptive statistics were used to describe the sample overall, and by physician speciality and treatment preference. Results Physicians (161 gastroenterologists; 57 GPs) were from different clinical settings in France (39.9%), Germany (28.4%) and the UK (31.7%). Overall, infliximab (33.0%) and adalimumab (32.1%) were selected more often as first treatment options than their biosimilars (17.0% and 9.6%, respectively). Gastroenterologists preferred biosimilars more frequently than GPs did (35.4% vs. 1.8%). More physicians who preferred biosimilars were from France (48.3%) than Germany (17.2%) or the UK (34.5%). In France and the UK, 93.8% of physicians who selected biosimilars worked in hospital settings; in Germany, 50.0% worked in clinics and 50.0% worked in practice settings with statutory and private patients. Physicians who preferred biosimilars treated more patients with UC in the preceding 12 months than those who preferred originators did (mean ± SD: 110.3 ± 113.9 vs. 94.0 ± 93.2). Although most physicians reported efficacy as a reason for biologic preference (93.6%), physicians who preferred originators were more likely to report good tolerability (73.8%) and patient preference (20.6%) and less likely to report affordability or availability (11.9%) than physicians who preferred biosimilars (63.8%, 10.3% and 44.8%, respectively). In patients who failed anti-TNF therapy, vedolizumab was the preferred treatment (78.9%), although this preference differed by speciality (gastroenterologists: 83.2%; GPs: 66.7%). Conclusion Originator biologics for treating patients with moderate-to-severe UC dominate the treatment landscape in Europe, driven primarily by efficacy, tolerability and patient preference. However, variations and differences in preferences by speciality and clinical setting may suggest a need to explore additional treatment options to manage disease symptoms among patients with UC.
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- 2020
188. DOP73 Efficacy and safety of escalation to tofacitinib 10 mg BID for patients with UC following loss of response on 5 mg BID maintenance therapy: Results from OCTAVE open-label, long-term extension study
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Haiying Zhang, M Zeroncio, Bruce E. Sands, Alan C. Moss, Irene Modesto, John Marshall, Nervin Lawendy, Alessandro Armuzzi, Leonardo Salese, Chinyu Su, Silvio Danese, W J Sandborn, and James O. Lindsay
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Oncology ,medicine.medical_specialty ,Tofacitinib ,business.industry ,Extension study ,Gastroenterology ,General Medicine ,Treatment failure ,Net reclassification improvement ,Maintenance therapy ,Internal medicine ,Disease remission ,medicine ,Herpes zoster disease ,Open label ,business - Abstract
Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib have been demonstrated in patients with moderate to severe UC in three Phase 3 studies (OCTAVE Induction 1 and 2 [NCT01465763; NCT01458951]; OCTAVE Sustain [NCT01458574]) [1]. Here, we present updated efficacy and safety data of tofacitinib dose escalation in patients with UC participating in an ongoing, open-label, long-term extension (OLE) study (OCTAVE Open, NCT01470612) [2]. Methods We present updated data from the dose-escalation subpopulation of the OLE study (as of May 2019; database not locked) comprising patients who achieved clinical response (CR) following 8 weeks of tofacitinib 10 mg twice daily (BID) induction therapy, entered OCTAVE Sustain receiving tofacitinib 5 mg BID, experienced treatment failure between Week 8 and Week 52, and subsequently entered OCTAVE Open with escalation to tofacitinib 10 mg BID. Treatment failure was defined as an increase of ≥3 points from maintenance study baseline total Mayo score, plus an increase of ≥1 point in both rectal bleeding subscore and centrally read endoscopic subscore (ES), and an absolute ES of ≥2 after ≥8 weeks of maintenance therapy. CR, mucosal healing (MH) and remission (R) were evaluated at Months 2, 12, 24 and 36 of OCTAVE Open (non-responder imputation and last observation carried forward [NRI-LOCF] and observed data). Safety was evaluated throughout the study. Results Of 944 patients enrolled in the OLE study, the dose escalation subpopulation comprised 59 patients. In these patients, CR, MH and R rates 36 months after dose escalation were, respectively, 40.7%, 39.0% and 30.5% for NRI-LOCF and 95.2%, 86.4% and 66.7% for observed data (Table). Of these 59 patients, 29 had prior tumour necrosis factor inhibitor (TNFi) failure; in these patients, CR, MH and R rates at Month 36 were, respectively, 51.7%, 51.7% and 41.4% for NRI-LOCF, and 100.0%, 92,3% and 75.0% for observed data. Incidence rates for safety events and pt-years’ exposure are reported in the table. Conclusion For most patients who lost initial CR to tofacitinib 10 mg BID induction therapy while on tofacitinib 5 mg BID maintenance therapy, including those with prior TNFi failure, dose-escalation back to 10 mg BID recaptured CR by Month 2 and was generally maintained over 3 years. The safety profile with tofacitinib 10 mg BID in the dose-escalation subpopulation was generally consistent with that in the overall study population, although there was a numerically higher rate of herpes zoster. These analyses are limited by low pt numbers and the absence of a comparator arm. References
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- 2020
189. DOP76 Corticosteroid sparing effects of ustekinumab therapy for ulcerative colitis through 2 years: UNIFI long-term extension
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Yiying Zhou, Bruce E. Sands, W J Sandborn, David Rowbotham, Jewel Johanns, Unifi Investigators, Rupert W. Leong, Ellen Scherl, Christopher D. O'Brien, Ramesh P. Arasaradnam, Silvio Danese, Colleen Marano, Maria T. Abreu, L Peyrin-Biroulet, and Hongyan Zhang
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Crohn's disease ,Pediatrics ,medicine.medical_specialty ,Intention-to-treat analysis ,Randomization ,medicine.drug_class ,business.industry ,ADRENAL CORTICOSTEROIDS ,Gastroenterology ,Ustekinumab therapy ,General Medicine ,medicine.disease ,Ulcerative colitis ,Ustekinumab ,medicine ,Corticosteroid ,business ,medicine.drug - Abstract
Background Ustekinumab (UST) is an IL12/23 blocker approved for Crohn’s disease and ulcerative colitis (UC). In the UNIFI maintenance study of patients with moderate–severe UC, >90% of the patients who achieved clinical response or remission at week 44 were able to eliminate corticosteroids, an important goal of therapy. In this analysis, we describe the corticosteroid (CS) sparing effects of UST treatment through week 92 among patients who were treated in the UNIFI long-term extension (LTE). Methods Responders to UST 8 weeks after IV induction entered the maintenance study and were randomised to UST 90mg SC (q12wks or q8wks) or PBO. Patients who did not respond to UST IV induction received a dose of UST 90mg SC at week 8 and were evaluated at week 16. Those in clinical response at week 16 (delayed responders), were not randomised on entry into the maintenance study and received UST 90mg q8wk. All patients who completed week 44 of the maintenance study were eligible to enter the LTE and continue to receive the same dose. Patients could receive UST dose adjustment during the LTE (q12wk to q8wk or q8wk to q8wk [sham dose adjustment]) from week 56 onward. Patients who remained on PBO were discontinued from the LTE after maintenance study unblinding. During the maintenance study, CS tapering was recommended for all patients receiving CS at maintenance baseline. At week 92 of the LTE, CS-free symptomatic remission rates and CS use were calculated using intention-to-treat analyses with a dose adjustment considered to be a treatment failure and with a dose adjustment not considered to be a treatment failure. Results Of the 284 patients in the randomised population who were treated with UST in the LTE, 139 were receiving CS at maintenance baseline. Of these, 92.8% (n = 129) were CS-free at week 92. CS-free symptomatic remission rates at week 92 are summarised in Table 1. Results were similar for the q8wk and q12wk maintenance doses. Of the UST-treated patients who were in symptomatic remission at week 92, 98.4% (182/185) were CS-free; similar results were seen when dose adjustment was not considered to be a treatment failure. Of the 116 delayed responders (non-randomised population) who continued to receive UST in the LTE, 92 patients were in symptomatic remission at week 92; of whom, 94.6% (87/92) were CS-free. Conclusion UST maintenance therapy, with both q8wk and q12wk dosing regimens, was effective in reducing and eliminating the use of CS in patients with UC. Nearly all patients in the LTE who were in symptomatic remission at week 92, were not taking steroids.
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- 2020
190. P341 Induction of response and remission: a network meta-analysis of induction studies comparing ontamalimab with other treatments for moderate-to-severe ulcerative colitis
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L Peyrin-Biroulet, Martina Goetsch, B Devine, Severine Vermeire, Silvio Danese, Kenneth J. Gorelick, Louise Charlotte Hartley, Bruce E. Sands, Remo Panaccione, Arpita Nag, and A Vickers
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Ozanimod ,medicine.medical_specialty ,Tofacitinib ,business.industry ,Gastroenterology ,General Medicine ,medicine.disease ,Ulcerative colitis ,Infliximab ,Golimumab ,Vedolizumab ,chemistry.chemical_compound ,chemistry ,Etrolizumab ,Internal medicine ,medicine ,Adalimumab ,business ,medicine.drug - Abstract
Background Decisions regarding the treatment of ulcerative colitis (UC) should be based on appropriate, high-quality evidence. In the absence of head-to-head trials, network meta-analysis (NMA) can be used to compare the efficacy and safety of several treatments. We conducted an NMA to compare the efficacy of ontamalimab (anti-MAdCAM-1) using its phase 2 data, with all other biologics and novel small molecules for which induction study data on response and remission in patients with UC were available. Methods A systematic literature review was conducted in November 2017 to identify published randomised controlled trials of induction treatment in patients with moderate-to-severe UC. An NMA of the identified studies was performed using random-effects models and methods based on NICE guidance. Odds ratios and 95% credible intervals were calculated to describe the relative differences between all treatments and placebo in terms of efficacy in inducing response and remission. Results were generated for anti-TNF-naïve and -experienced populations. Results A total of 14 phase 2 and phase 3 induction studies of the following agents were included: adalimumab (160/80 mg), etrolizumab (100 mg and 300 mg), golimumab (200/100 mg), infliximab (5 mg), ontamalimab (22.5 mg and 75 mg), ozanimod (0.5 mg and 1 mg), tofacitinib (10 mg) and vedolizumab (300 mg). The definitions of response and remission used across trials were consistent. Between-study homogeneity was good and enabled pooling of results. Figure 1 shows odds ratios for induction of response and remission with treatments relative to placebo in anti-TNF-naïve and -experienced patients. All treatments, including ontamalimab, significantly differentiated from placebo in anti-TNF-naïve patients, with the exception of etrolizumab and ozanimod for response and remission, respectively. Tofacitinib (p = 0.0043) and infliximab (p = 0.0013) were superior to adalimumab in inducing response; whereas etrolizumab 100 mg (p = 0.0377), as well as tofacitinib (p = 0.0287) and infliximab (p = 0.0163), was superior to adalimumab in inducing remission. Conclusion This study suggests ontamalimab and most other treatments induce response and remission better than placebo. Although conducted before any large-scale head-to-head trials of these drugs, the study suggests a few treatments could be superior to adalimumab in terms of efficacy. However, varying endpoint timings, the combination of phase 2 and 3 data, and lack of control for placebo response could underscore large variances in the data and preclude firm conclusions being drawn.
- Published
- 2020
191. P463 Induction of endoscopic response: a network meta-analysis of induction studies comparing ontamalimab with other treatments for moderate-to-severe ulcerative colitis
- Author
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Louise Charlotte Hartley, Severine Vermeire, A Vickers, Arpita Nag, Kenneth J. Gorelick, Silvio Danese, Martina Goetsch, B Devine, Bruce E. Sands, L Peyrin-Biroulet, and Remo Panaccione
- Subjects
Ozanimod ,medicine.medical_specialty ,Tofacitinib ,business.industry ,Gastroenterology ,General Medicine ,medicine.disease ,Ulcerative colitis ,Infliximab ,Vedolizumab ,chemistry.chemical_compound ,chemistry ,Etrolizumab ,Meta-analysis ,Internal medicine ,Adalimumab ,medicine ,business ,medicine.drug - Abstract
Background Clinicians, patients, payers and policymakers require relevant, high-quality evidence to support decision-making regarding the treatment of ulcerative colitis (UC). In the absence of head-to-head trials, network meta-analysis (NMA) can be used to compare treatments. We conducted an NMA to compare the efficacy of ontamalimab (anti-MAdCAM-1) using its phase 2 data, with all biologics and novel small molecules for which induction study data on endoscopic response were available. Methods A systematic literature review was conducted in November 2017 to identify published randomised controlled trials of induction treatment in patients with moderate-to-severe UC. An NMA of the identified studies was performed using random-effects models and methods based on NICE guidance. Odds ratios and 95% credible intervals were calculated to describe the relative differences between treatments and placebo in terms of efficacy in inducing endoscopic response. Results were examined by anti-TNF status (naïve vs. experienced). Results In total, 15 phase 2 and phase 3 induction studies of the following agents were available and included: adalimumab (160/80mg), etrolizumab (100mg and 300mg), golimumab (200/100mg), infliximab (5mg), ontamalimab (22.5mg and 75mg), ozanimod (0.5mg and 1mg), tofacitinib (10mg) and vedolizumab (300mg). The definition of endoscopic response (improvement) in all trials was a Mayo endoscopic subscore of ≤1. Homogeneity between studies was good, enabling pooling of results. Figure 1 shows odds ratios for induction of endoscopic response with treatments relative to placebo in anti-TNF-naïve and -experienced patients. All treatments performed significantly better than placebo in anti-TNF-naïve patients, with the exception of both doses of etrolizumab and ozanimod 0.5 mg. Significant differences between some treatments were observed; specifically, ontamalimab 22.5 mg (p = 0.0277), tofacitinib 10 mg (p = 0.0233) and infliximab 5 mg (p = 0.0047) were all superior to adalimumab 160/80 mg. Conclusion This study suggests that ontamalimab, infliximab and tofacitinib could be superior to adalimumab in inducing endoscopic healing, although it was conducted before any large-scale head-to-head trials of these drugs. Furthermore, large variances due to differing endpoint timings, the combination of phase 2 and phase 3 data, and lack of control for placebo response rates preclude firm conclusions being drawn.
- Published
- 2020
192. P068 MIRIKIZUMAB TREATMENT IMPROVES BOWEL MOVEMENT URGENCY IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS
- Author
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Nathan Morris, Vipin Arora, Marla Dubinsky, Trevor Lissoos, Yan Dong, Severine Vermeire, Scott D. Lee, April N. Naegeli, Bruce E. Sands, Maria T. Abreu, and Remo Panaccione
- Subjects
medicine.medical_specialty ,Hepatology ,medicine.drug_class ,business.industry ,Gastroenterology ,medicine.disease ,Monoclonal antibody ,Ulcerative colitis ,Internal medicine ,medicine ,Interleukin 23 ,Defecation ,Immunology and Allergy ,In patient ,business ,Imputation (genetics) - Abstract
Background Mirikizumab (miri; LY3074828) is a humanized monoclonal antibody directed against the p19 subunit of IL-23, which demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial (NCT02589665) in patients with ulcerative colitis (UC). Bowel movement urgency is one of the most bothersome symptoms experienced by patients with UC with an often-overlooked impact of their quality of life (QoL). Here we show the effect of miri on patient-reported urgency. Methods Patients were randomized 1:1:1:1 to receive intravenous placebo (PBO), miri 50mg or 200mg with possibility of exposure-based dose increases, or fixed miri 600mg every 4 weeks (Q4W), with efficacy assessment at Week 12. Patients who achieved clinical response to miri at Week 12 (decrease in 9-point Mayo score ≥ 2 points and ≥ 35% from baseline, and either a decrease in rectal bleeding (RB) subscore ≥1 or RB subscore of 0 or 1) were re-randomized 1:1 to double-blind maintenance treatment with miri 200mg subcutaneously (SC) every 4 (Q4W) or 12 (Q12W) weeks and were treated through Week 52. Patients reported daily symptoms, including absence or presence of bowel movement urgency. Logistic regression analysis was conducted to evaluate the treatment differences in absence of urgency among patients who had urgency at baseline for the first 12 weeks, with absence of urgency defined as no urgency symptom for three consecutive days prior to each scheduled visit. The proportion of patients with no urgency was calculated for the maintenance period among patients who had urgency at baseline and reached clinical response at Week 12, irrespective of urgency status at Week 12. Patients who had missing urgency data were imputed as having experienced urgency. Results At Week 12 patients in the 200mg and 600mg miri groups showed significantly higher rates of achieving absence of urgency compared to the PBO group (PBO: 10/55, 18.2% [CI: 8.0–28.4]; miri 50mg: 18/59, 30.5% [CI: 18.8–42.3]; 200mg: 22/56, 39.3% [CI: 26.5, 52.1], p=0.016; 600mg: 22/51, 43.1% [CI: 29.5, 56.7], p=0.006, Figure 1). Induction clinical responders who continued onto the maintenance period sustained this improvement in urgency with minimal variation (Figure 2). Conclusion In patients who reported bowel movement urgency at baseline, mirikizumab treatment resulted in significantly higher proportions of patients with no bowel movement urgency compared to placebo at Week 12, with numerical improvement observed as early as Week 4 and statistically significant improvement by Week 8. The reduction in bowel movement urgency was sustained through Week 52.
- Published
- 2020
193. Novel Therapies in Inflammatory Bowel Disease: An Evaluation of the Evidence
- Author
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Neeraj Narula, Bruce E. Sands, and David T. Rubin
- Subjects
0301 basic medicine ,Budesonide ,biology ,business.industry ,Inflammation ,Disease ,medicine.disease ,Ulcerative colitis ,Inflammatory bowel disease ,Vedolizumab ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immunology ,medicine ,Addressin ,biology.protein ,030211 gastroenterology & hepatology ,medicine.symptom ,Janus kinase ,business ,medicine.drug - Abstract
The introduction of anti-tumor necrosis factor (anti-TNF) therapies for both Crohn’s disease (CD) and ulcerative colitis (UC) was a landmark in the management of these debilitating diseases. For a substantial proportion of patients, anti-TNF therapies have reduced relapse rates and allowed mucosal healing and, as a result, improved long-term outcomes. However, research into novel therapies for inflammatory bowel diseases (IBD) has been challenging and positive early trials have not always translated to proof of efficacy and safety in late-phase studies. As an alternative to targeting inflammation through cytokines (e.g., TNF), reducing the ability of lymphocytes to generate an inflammatory response is now a therapeutic reality with the availability of the integrin inhibitors. The “gut-selective” vedolizumab is now an established treatment option for UC and CD either before, or after, anti-TNF therapy. Other agents in development that target lymphocyte adhesion include novel anti-integrin and anti-mucosal vascular addressin cell adhesion molecule-1 (anti-MadCAM-1) agents, or target lymphocyte trafficking (e.g. anti-sphingosine 1-phosphate therapies). In addition however, there are novel ways of reducing inflammation by targeting downstream signaling (e.g., Janus kinase inhibitors), the use of antisense oligonucleotides to transforming growth factor-β, or by targeting novel cytokines such as interleukin-12/23 or interleukin-6 that have been implicated in the pathogenesis of IBD. The introduction of a novel formulation of budesonide (budesonide MMX) for UC illustrates that for patients with mild IBD there is also a need for novel therapies and agents in development, include other second-generation corticosteroids that are associated with reduced systemic delivery and approaches to enhance the mucosal barrier or alter the microbiota. Many new and effective therapies are in development for IBD and, if positive in late phase trials, are anticipated to be available within the next decade. Having a number of different agents available will allow the clinician to offer the best therapies for an individual patient. This will likely have huge implications not only for patients and clinicians, but for society as a whole.
- Published
- 2016
194. Development of an index to define overall disease severity in IBD
- Author
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Richard B. Gearry, Julián Panés, Remo Panaccione, Gerassimos J. Mantzaris, Curt Tysk, Charles N. Bernstein, Stefan Schreiber, Anne M. Griffiths, Edward V. Loftus, Siew C. Ng, Ioannis E. Koutroubakis, Cynthia B. Whitman, Simon Travis, Mark S. Silverberg, Laurent Peyrin-Biroulet, Brian G. Feagan, William J. Sandborn, Gerhard Rogler, Bruce E. Sands, Silvio Danese, Geert R. D'Haens, Balfour R. Sartor, Jean-Frederic Colombel, Stephen B. Hanauer, Corey A. Siegel, Francesco Pallone, Walter Reinisch, Jonas Halfvarson, Dermot P.B. McGovern, Bjørn Moum, Peter L. Lakatos, Colm O'Morain, Brennan Spiegel, Robert H. Riddell, Christoph Gasche, Wolfgang Kruis, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Siegel, Ca, Whitman, Cb, Spiegel, Bmr, Feagan, B, Sands, B, Loftus, Ev, Panaccione, R, D'Haens, G, Bernstein, Cn, Gearry, R, Ng, Sc, Mantzaris, Gj, Sartor, B, Silverberg, M, Riddell, R, Koutroubakis, Ie, O'Morain, C, Lakatos, Pl, Mcgovern, Dpb, Halfvarson, J, Reinisch, W, Rogler, G, Kruis, W, Tysk, C, Schreiber, S, Danese, S, Sandborn, W, Griffiths, A, Moum, B, Gasche, C, Pallone, F, Travis, S, Panes, J, Colombel, Jf, Hanauer, S, and Peyrin-Biroulet, L
- Subjects
Adult ,Male ,medicine.medical_specialty ,Abdominal Abscess ,Activities of daily living ,Delphi Technique ,Disease ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Disease severity ,Internal medicine ,Activities of Daily Living ,Intestinal Fistula ,Humans ,Medicine ,In patient ,Intestinal Mucosa ,Abscess ,Aged ,Biological Products ,Crohn's disease ,biology ,business.industry ,C-reactive protein ,Gastroenterology ,Middle Aged ,medicine.disease ,Ulcerative colitis ,Surgery ,C-Reactive Protein ,030220 oncology & carcinogenesis ,biology.protein ,Colitis, Ulcerative ,Female ,030211 gastroenterology & hepatology ,Symptom Assessment ,business - Abstract
Background and aimDisease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC.MethodsUsing a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute.ResultsFor CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities.ConclusionsBased on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.
- Published
- 2016
195. 832 Pharmacokinetics and Exposure-Response Relationships of Ustekinumab in Patients With Ulcerative Colitis: Results From the UNIFI Induction and Maintenance Studies
- Author
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Christopher B. O'Brien, Jewel Johanns, Tadakazu Hisamatsu, Silvio Danese, Colleen Marano, Maria T. Abreu, Zhenhua Xu, Rupert W. Leong, Gert Van Assche, Omoniyi J. Adedokun, Hongyan Zhang, Philippe Szapary, Bruce E. Sands, and William J. Sandborn
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Gastroenterology ,Exposure response relationships ,medicine.disease ,Ulcerative colitis ,Pharmacokinetics ,Internal medicine ,Ustekinumab ,medicine ,In patient ,business ,medicine.drug - Published
- 2019
196. 697 Safety of Ustekinumab in Inflammatory Bowel Diseases: Integrated Safety Analysis of Results From Phase 2 and 3 Studies in Crohn's Disease and Ulcerative Colitis
- Author
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Bruce E. Sands, Christopher D. O'Brien, Elyssa Ott, Christopher Gasink, Silvio Danese, Colleen Marano, Ilia Tikhonov, Sheri Volger, Yiying Zhou, William J. Sandborn, and Subrata Ghosh
- Subjects
medicine.medical_specialty ,Crohn's disease ,Hepatology ,business.industry ,Gastroenterology ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,Internal medicine ,Ustekinumab ,medicine ,business ,medicine.drug - Published
- 2019
197. 749 Medication Use and Comorbidities Among Elderly as Compared to Younger Patients With Inflammatory Bowel Disease in the TARGET-IBD Cohort
- Author
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Sumona Saha, Millie D. Long, Miguel Regueiro, Edward L. Barnes, Marla Dubinsky, Julia M. Crawford, Derek Gazis, Bruce E. Sands, John S. Hanson, David T. Rubin, and Corey A. Siegel
- Subjects
Medication use ,medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Cohort ,Gastroenterology ,Medicine ,business ,medicine.disease ,Inflammatory bowel disease - Published
- 2019
198. 842 Impact of Response and Inflammatory Burden at Start of Maintenance Therapy on Clinical Efficacy of Ustekinumab Dosing Regimen in UC: Week 44 Results From UNIFI
- Author
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Philippe Szapary, Maria T. Abreu, David Rowbotham, Rupert W. Leong, Bruce E. Sands, Christopher D. O'Brien, Remo Panaccione, Laurent Peyrin-Biroulet, Silvio Danese, Colleen Marano, Ramesh P. Arasaradnam, Jewel Johanns, and Hongyan Zhang
- Subjects
medicine.medical_specialty ,Hepatology ,Maintenance therapy ,business.industry ,Internal medicine ,Ustekinumab ,Gastroenterology ,Dosing regimen ,medicine ,Clinical efficacy ,business ,medicine.drug - Published
- 2019
199. 642 Effects of Ustekinumab Maintenance Therapy on Endoscopic Improvement and Histologic Improvement in the UNIFI Phase 3 Study in Ulcerative Colitis
- Author
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Gert De Hertogh, Hongyan Zhang, Katherine Li, William J. Sandborn, Brian G. Feagan, Joshua R. Friedman, Feifei Yang, Colleen Marano, Laurent Peyrin-Biroulet, and Bruce E. Sands
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Gastroenterology ,Phases of clinical research ,medicine.disease ,Ulcerative colitis ,Maintenance therapy ,Internal medicine ,Ustekinumab ,Medicine ,business ,medicine.drug - Published
- 2019
200. What Is the Role of the Inflammatory Bowel Disease Panel in Diagnosis and Treatment?
- Author
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Bruce E. Sands and Millie D. Long
- Subjects
Hepatology ,business.industry ,Gastroenterology ,Disease Management ,Inflammatory Bowel Diseases ,medicine.disease ,Bioinformatics ,Inflammatory bowel disease ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,030225 pediatrics ,medicine ,Humans ,Serologic Tests ,030211 gastroenterology & hepatology ,business - Published
- 2018
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