Severe IBD: What to Do When Anti- TNFs Don t Work?
|
|
- Lester Scott
- 6 years ago
- Views:
Transcription
1 Severe IBD: What to Do When Anti- TNFs Don t Work? David T. Rubin, MD, FACG Professor of Medicine Co-Director, Inflammatory Bowel Disease Center Interim Chief, Section of Gastroenterology, Hepatology and Learning Objectives At the conclusion of this presentation, learners will: 1. Incorporate the emerging understanding regarding pathogenesis of loss of response in patients on anti-tnf therapy. 2. Develop an approach to the pro-active assessment of monitoring anti-tnf therapy of IBD. 3. Understand the current literature about anti-integrin therapy (such as natalizumab or vedolizumab) in patients with IBD. 1
2 Anti-TNF Therapies for Inflammatory Bowel Disease CD CD UC UC CD UC Modified from van Schouwenburg, P. A. et al. (2013) Immunogenicity of anti-tnf biologic therapies for rheumatoid arthritis Nat. Rev. Rheumatol. doi: /nrrheum Induction Treatment with anti-tnfα Agents Clinical remission in anti-tnfα naïve patients (ITT) (CDAI 150) (for Targan study CDAI < 150) REMISSION AT 4 WEEKS 1,2,3 Targan 1 ** Schreiber 2 ** CLASSIC I 3 PRECiSE 1 2 Patients(%) * NS NS * * * NS NS * * 48.2* 36.5* 25.0* 25.0* 28.6* 26.7* 18.2* * Targan et al. N Engl J Med 1997;337: UCB Data on File. 3. Hanauer et al. Gastroenterology 2006;130:
3 0 David T. Rubin, MD, FACG Maintenance Treatment with anti-tnf- α in CD Moderate to Severely Active IBD Most Failing Immune modulators Long Duration of Disease ACCENT I 1 Infliximab CDAI 70 & 25% reduction 5mg/kg q8 54 weeks 100% 100% CHARM 2 Adalimumab CDAI 70 40mg eow 56 weeks 100% PRECiSE 2&3 3,4 Cert pegol CDAI 100 & HBI 400mg q4 80 weeks 52% 38% 54% 43% 63% 54%* 44%* 0 0 0% 0% 0% Months Months IFX Placebo ADA Placebo 1. Hanauer et al. Lancet 2002;359: Colombel et al. Gastroenterology 2007;132: Schreiber et al. Gut 2006;55(Suppl V):A Lichtenstein et al. Gastroenterology 2007;132(Suppl 2):A502 (Abstract T1264) Months certolizumab pegol certolizumab pegol open label Placebo Efficacy of Adalimumab for Induction of Remission in UC Fraction of Pts (5) doses of ADA then endpoints measured at week 8 P = NS P = NS *P <.05 vs. PBO * Remission Response Mucosal Healing PBO (N = 130) ADA 80/40/40/40 (N = 130) ADA 160/80/40/40 (N = 130) The intent-to-treat (ITT) population included only the 390 patients randomized after the protocol amendment. Reinisch 6 W, et al. Gut. 2011;60(6):
4 Golimumab for the Induction of Moderate to Severe UC: PURSUIT Golimumab: A fully human monoclonal antibody against TNF-α Phase 3: Clinical Response and Remission at Week 6 response remission *P< vs placebo 51.8* 55.0* Placebo (n=256) mg 100 mg (n=257) 18.7* 17.8* 400 mg 200 mg (n=258) Sandborn WJ, et al. Gastroenterology doi:pii: S (13) epub ahead of print. Why Do Patients With IBD Not Respond To Their Medications? Primary Nonresponse Drug/mechanism just doesn t work Wrong diagnosis Infection Ischemia Crohn s disease Wrong dose Not enough Too much? Other pk issues Wrong delivery Rationale Allergy/intolerance Secondary Nonresponse Change in dose (by you) Change in delivery Change in physiology Does disease change over time? Intentional nonadherence Episodic dosing strategy Denial Fear of therapy Unintentional nonadherence Can t afford medication Inconvenient dosing regimen 4
5 Why Do Patients With IBD Not Respond To Their Medications? Primary Nonresponse Drug/mechanism just doesn t work Wrong diagnosis Infection Ischemia Crohn s disease Wrong dose Not enough Too much? Other pk issues Wrong delivery Rationale Allergy/intolerance Secondary Nonresponse Change in dose (by you) Change in delivery Change in physiology Does disease change over time? Intentional nonadherence Episodic dosing strategy Denial Fear of therapy Unintentional nonadherence Can t afford medication Inconvenient dosing regimen Factors Affecting the Pharmacokinetics of Monoclonal Antibodies Presence of ADAs Concomitant use of IS High baseline TNF-α Low albumin High baseline CRP Body size Gender Impact on Pharmacokinetics Decreases serum mabs Threefold-increased d clearance Worse clinical outcomes Reduces formation Increases serum mabs Decreases mab clearance Better clinical outcomes May decrease mabs by increasing clearance Increases clearance Worse clinical outcomes Increases clearance High BMI may increase clearance Males have higher clearance Ordas I et al. Clin Pharmacol Ther. 2012;91:635. mab, monoclonal antibody; ADA, antidrug antibody 5
6 Rapid IFX clearance: Mechanism of Non Response in UC Kevans D, et al. Presented at DDW; May 19, Fecal Loss of Infliximab (IFX) is a Cause of Lack of Response in Severe Colitis 11 pts with colitis (8 UC, 3 CD) Compared to responders, non-responders to IFX had: Higher fecal IFX concentration at day 1 (P=0.02) Lower serum IFX concentration at day 14 (P=0.03) Brandse JF, et al. Presented at DDW, May 18, Abstract
7 The Challenge of Immunogenicity All biologic therapies, regardless of humanization, induce immunogenicity Immunogenicity may result in hypersensitivity reactions and loss of response to therapy Subtherapeutic drug concentrations lead to lack of efficacy Methods to reduce immunogenicity: Maintenance therapy with drug Loading dose of drug Concomitant timmune-modulatory therapy Emerging: Appreciation for distinction between low titer and high titer antibodies Treatment to overcome low titer antibodies. Immunogenicity of TNF Antagonists with and without Concomitant Immune Modulators (IMS) Patients, % Episodic Maintenance Scheduled Maintenance IMS- IMS+ IMS- IMS+ Infliximab 1 (CD 5 mg/kg) (CD 10 mg/kg) 38% 16% 11% 8% 7% 4% Infliximab 2 (UC 5 mg/kg) 19% 2% (UC 10 mg/kg) No data 9% 4% Certolizumab 3 (PRECiSE I) 10% 4% Certolizumab 4 (PRECiSE II) 24% 8% 12% 2% Adalimumab 5 (RA, all doses) 12% 1% No data Adalimumab 6 (CLASSIC II) 4% 0% Golimumab 7 (RA) No data 13.1% 4.3% 1 Hanauer et al. Clin Gastroenterol Hepatol. 2004; 2 Sandborn et al. DDW 2007 Poster and abstract T1273; 3 Sandborn WJ, et al. N Engl J Med. 2007; 4 Schreiber S, et al. N Engl J Med. 2007; 5 Summary of Product Characteristics for adalimumab. Abbott Laboratories. July 2007; 6 Sandborn WJ, et al. Gut Keystone et al. J Rheumatol May 15. [Epub ahead of print] 7
8 Immunogenicity of TNF Antagonists with and without Concomitant Immune Modulators (IMS) Patients, % Episodic Maintenance Scheduled Maintenance IMS- IMS+ IMS- IMS+ Infliximab 1 (CD 5 mg/kg) (CD 10 mg/kg) 38% 16% 11% 8% 7% 4% Infliximab 2 (UC 5 mg/kg) 19% 2% (UC 10 mg/kg) No data 9% 4% Certolizumab 3 (PRECiSE I) 10% 4% Certolizumab 4 (PRECiSE II) 24% 8% 12% 2% Adalimumab 5 (RA, all doses) 12% 1% No data Adalimumab 6 (CLASSIC II) 4% 0% Golimumab 7 (RA) No data 13.1% 4.3% 1 Hanauer et al. Clin Gastroenterol Hepatol. 2004; 2 Sandborn et al. DDW 2007 Poster and abstract T1273; 3 Sandborn WJ, et al. N Engl J Med. 2007; 4 Schreiber S, et al. N Engl J Med. 2007; 5 Summary of Product Characteristics for adalimumab. Abbott Laboratories. July 2007; 6 Sandborn WJ, et al. Gut Keystone et al. J Rheumatol May 15. [Epub ahead of print] Who is at risk for anti-drug antibodies? The patient receiving episodic therapy Intentional ti Unintentional: break in therapy due to coverage issues or complication Pseudo-episodic therapy Sub-therapeutic serum drug levels 1 The patient with drug clearance between doses The patient who developed anti-drug antibodies previously 1 Vermeire S et al. Gut. 2007;56(9);
9 Switching to Another Biologic Therapy What to choose and when to choose it? Evidence only exists in one direction (infliximab first), assumption is the opposite is true Primary non-responder: anti-tnfα loading dose with no response: Where is the drug going? try a different mechanism (not a different anti-tnfα therapy!) Primary responder now relapsing Assess for inflammation If suspect immunogenicity, switching to second anti-tnf is reasonable 1-3 If not immunogenicity, consider a different mechanism of treatment 1. Sandborn, et al. Ann Int Med, Panaccione R, et al. DDW 2008: # Rutgeerts PJ, et al. DDW 2008: #494 Interpretation of Infliximab Levels and Antibodies to Infliximab in a Patient Losing Response Infliximab i Level Antibodies to Treatment Infliximab recommendation Elevated Absent Switch treatment mechanism Elevated Present Unclear, consider switching to another TNF-inhibitor Not elevated Absent Adjust dose, interval of infliximab Not elevated Present Switch to another TNF-inhibitor Afif, et al. Am J Gastroenterol ;105(5):
10 Switching Between TNF Inhibitors: Rheumatoid Arthritis Experience Response to a second inhibitor is lower relative to first 1 Response to a second inhibitor will be comparable if initial discontinuation was due to adverse events 1, 2 Patients who do not respond to 2 TNF inhibitors are not lk likely l to respond to a third 2 1. Gomez-Reino et al. Arthritis Research & Therapy. 2006;8:R29 2. Solau-Gervais et al. Rheumatology. 2006;epub ahead of print. Non-Anti-TNF Mechanisms of Management for the Patient Failing anti-tnf Therapy Confirm Inflammation First Crohn s Disease Natalizumab Methotrexate Surgery Including staged approaches or diversion for induction of remission Bowel rest Less evidence: Mycophenolate Tacrolimus Ulcerative Colitis Cyclosporine Tacrolimus Surgery Don t Forget about Clinical Trials! 10
11 Leukocyte Trafficking Inhibition leukocyte Brain Bone marrow integrins natalizumab α 4 β 1 α 4 β 7 Gut natalizumab Vedolizumab, rhumab-beta7 addressins PF VCAM-1 MadCAM-1 endothelium Updated Utilization and Safety Results of Natalizumab in CD and MS (TOUCH, CD INFORM, TYGRIS & Pregnancy Registry Studies) 118,100 patients have received globally (post- marketing) as of 6/30/2013 Predominantly MS patients PML (Progressive Multifocal Leukoencephalopathy) Rare but serious 410 cases reported globally as of 01-Oct- 2013; 23% have died Longer duration and prior immunosuppressant use increases risk Risk for patients treated months similar to rates seen in clinical trials Limited safety data beyond 4 yrs of treatment No known treatment or prevention interventions for PML (accessed 12-Dec-2011); PML Incidence according to Elan Pharmaceuticals at 04- Nov
12 What happens to the patients who receive natalizumab in the current post-tnf paradigm? Chicago Experience Sakuraba et al. Inflamm Bowel Dis 2013; ;19(3): Recommendations for JCV Antibody Testing Testing prior to treatment with natalizumab If positive, consider retesting. If confirmed, option is treatment with natalizumab for 9-12 months If negative, may treat with natalizumab, retest every 6 months If converts to positive, stop therapy The benefit and safety of a drug holiday and restarting after resetting the exposure has not been tested in Crohn s disease Vedolizumab (expected approval Q2 2014) does not have PML associated with it. 12
13 Vedolizumab for Ulcerative Colitis Primary Endpoints (GEMINI I) Patients (%) Week 6 P< Clinical response (Primary endpoint) Placebo, n=149 VDZ, n=225 Patients (%) Feagan BG et al. N Engl J Med Aug 22;369(8): Week P< Clinical remission (Primary endpoint) P values are vs placebo. All patients were Week 6 responders P< Placebo, n=126 VDZ Q8, n=122 VDZ Q4, n=125 Vedolizumab for Crohn s Disease Primary Endpoints (Gemini II and III) Primary Efficacy Endpoint Placebo Clinical remission at Week 6 (GEMINI II) Clinical remission at Week 6 in anti- TNF failures (GEMINI III) Enhanced clinical response at Week 6 (GEMINI II) VDZ VDZ Q8 VDZ Q4 P Value/ Induction Weeks Weeks 95% CI a 7% 15% < % 15% NS 26% 31% NS Clinical remission at Week 52 22% -- 39% 36% Clinical remission at Week 52 in anti-tnf failures 13% -- 28% 27% <0.001 < , , 26.9 NS=not significant. a 95% CI for difference from placebo. Although these endpoints were prespecified, P values are not provided because multiple testing adjustments were not made. Sandborn WJ et al. N Engl J Med Aug 22;369(8):
14 Clinical Assessment of Disease Control Routine inquiry regarding stability of disease control (stable maintenance between doses) Strict adherence to maintenance regimen Ongoing laboratory assessment of clinical stability Increasing utilization of surrogate markers of inflammatory activity it (fecal calprotectin) ti Future Strategies: Smarter Treatment Selection and Therapeutic Monitoring Selecting patients more likely to respond to anti-tnf panca negative? Specific polymorphisms? Fecal protein assessment? Therapeutic monitoring Can allow dose adjustment prior to loss of response to drug and clinical relapse Identifies es patients ts at high risk of subsequent ADA and loss of response 1 May allow for dose reduction of anti-tnf therapy Less drug, less direct costs Possibly avoiding AEs associated with high therapeutic exposure (?) 1 Vermeire S et al. Gut. 2007;56(9);
15 Summary: What to do when the patient loses response to anti-tnf therapy in IBD Optimize use in the first place: choose the right patients, treat early, monitor carefully Confirm inflammation Distinguish between primary and secondary loss of response Use therapeutic monitoring to assist with assessment Understand emerging and new therapies Don t forget surgery! 15
The Refractory Crohn s Disease
The Refractory Crohn s Disease Patient David T. Rubin, MD, FACG Professor of Medicine Co-Director, Inflammatory Bowel Disease Center Interim Chief, Section of Gastroenterology, Hepatology and Nutrition
More informationSeptember 12, 2015 Millie D. Long MD, MPH, FACG
Update on Biologic Therapy in 2015 September 12, 2015 Millie D. Long MD, MPH, FACG Assistant Professor of Medicine Inflammatory Bowel Disease Center University of North Carolina-Chapel Hill Outline Crohn
More informationMono or Combination Therapy with. Individualized Approach
Mono Combination Therapy with Biologics i in IBD: Developing an Individualized Approach David T. Rubin, MD, FACG Co-Direct, Inflammaty Bowel Disease Center Fellowship Program Direct University of Chicago
More informationManagement of Refractory Crohn s Disease
Management of Refractory Crohn s Disease @IBDMD David T. Rubin, MD, FACG, FASGE Joseph B. Kirsner Professor of Medicine Chief, Section of Gastroenterology, Hepatology and Nutrition Disclosures Consultant
More informationAn Update on the Biologic Treatment for Patients with Inflammatory Bowel Disease. David A. Schwartz, MD
An Update on the Biologic Treatment for Patients with Inflammatory Bowel Disease David A. Schwartz, MD Director, Inflammatory Bowel Disease Center Associate Professor of Medicine Vanderbilt University
More informationUpdate on Biologics in Ulcerative Colitis. Scott Plevy, MD University of North Carolina Chapel Hill, NC
Update on Biologics in Ulcerative Colitis Scott Plevy, MD University of North Carolina Chapel Hill, NC Objectives Discuss the latest advances in the pharmacologic management of ulcerative colitis Describe
More informationImmunogenicity of Biologic Agents and How to Prevent Sensitization
Immunogenicity of Biologic Agents and How to Prevent Sensitization William J. Sandborn, MD Professor and Chief, Division of Gastroenterology Director, UCSD IBD Center La Jolla, California, USA Learning
More informationIBD Updates. Themes in IBD IBD management journey. New tools for therapeutic monitoring. First-line treatment in IBD
IBD Updates Maria T. Abreu, MD University of Miami Miller School of Medicine Miami, Florida Themes in IBD 213 First-line treatment in IBD New tools for therapeutic monitoring Biologic therapy for CD and
More informationRecent Advances in the Management of Refractory IBD
Recent Advances in the Management of Refractory IBD Raina Shivashankar, M.D. Assistant Professor of Medicine Division of Gastroenterology and Hepatology Thomas Jefferson University Philadelphia, PA Outline
More informationPositioning New Therapies
Positioning New Therapies Stephen Hanauer, MD Professor of Medicine Medical Director, Digestive Disease Center Northwestern Medicine Chicago, Illinois Speaker Disclosure Stephen Hanauer, MD has disclosed
More informationBiologic Therapy for Inflammatory. Is Top-Down Too Top-Heavy? S. Devi Rampertab, MD, FACG, AGAF Associate Professor of Medicine University of Florida
Biologic Therapy for Inflammatory Bowel Disease: Is Top-Down Too Top-Heavy? S. Devi Rampertab, MD, FACG, AGAF Associate Professor of Medicine University of Florida Learning Objectives Evaluate evidence
More informationEmerging g therapies for IBD: A practical approach to positioning. Sequential Therapies for IBD
Emerging g therapies for IBD: A practical approach to positioning Stephen B. Hanauer, MD Sequential Therapies for IBD Disease Severity at Presentation Severe Anti-TNF +/IS Cyclosporine (UC) Colectomy (UC)
More informationDisclosures. What Do I Do When Anti-TNF Therapy Is Not Working Anymore? Fadi Hamid, M.D. Saint Luke s GI Specialists
What Do I Do When Anti-TNF Therapy Is Not Working Anymore? Fadi Hamid, M.D. Saint Luke s GI Specialists Disclosures No financial relationships to disclose. 1 Learning Objectives Case 24M with ileocolonic
More informationBiologics in IBD. Brian P. Bosworth, MD, NYSGEF Associate Professor of Medicine Weill Cornell Medical College
Biologics in IBD Brian P. Bosworth, MD, NYSGEF Associate Professor of Medicine Weill Cornell Medical College Case 30 year old man diagnosed with ulcerative proctitis diagnosed in 2003 Had been maintained
More informationNew and Future Adhesion Molecule Based Therapies in IBD
New and Future Adhesion Molecule Based Therapies in IBD Brian G. Feagan Professor of Medicine, Epidemiology and Biostatistics University of Western Ontario Robarts Clinical Trials London, Ontario, Canada
More informationSelective leucocyte trafficking inhibitors for treatment of IBD
Selective leucocyte trafficking inhibitors for treatment of IBD Séverine Vermeire MD, PhD Department of Gastroenterology University Hospitals Leuven Belgium Migration of Leucocytes plays a key role in
More informationJohn F. Valentine, MD Inflammatory Bowel Disease Program University of Utah
John F. Valentine, MD Inflammatory Bowel Disease Program University of Utah Hawaii 1/20/2017 DISCLOSURES Research Support: NIH, Pfizer, Celgene, AbbVie, Roche/Genentech, Takeda, CCFA OBJECTIVES Review
More informationNew treatment options in IBD: today and the future. Silvio Danese Istituto Clinico Humanitas, Milan, Italy
New treatment options in IBD: today and the future Silvio Danese Istituto Clinico Humanitas, Milan, Italy Date of preparation: October 2014 GLO/EYV/2014-00010h Overview of the late-stage IBD drug pipeline*
More informationBiologic Therapy for Ulcerative Colitis in 2015
5/6/215 Biologic Therapy for Ulcerative Colitis in 215 John K. Marshall MD MSc FRCPC AGAF Division of Gastroenterology McMaster University Bressler B, Marshall JK, et al. Gastroenterology 215;148: 135-58
More informationEmerging Therapies in IBD 2006
Overview Emerging Therapies in IBD 26 David T. Rubin, MD Assistant Professor of Medicine Inflammatory Bowel Disease Center University of Chicago Describe the unmet needs of therapy in IBD Emerging biologic
More informationPosition of Biologics in IBD Circa 2006: Top Down vs. Step Up Therapy
Position of Biologics in IBD Circa 2006: Top Down vs. Step Up Therapy Stephen B. Hanauer, MD University of Chicago Potential Conflicts: Centocor/Schering, Abbott, UCB, Elan, Berlex, PDL Goals of Treatment
More informationBeyond Anti TNFs: positioning of other biologics for Crohn s disease. Christina Ha, MD Cedars Sinai Inflammatory Bowel Disease Center
Beyond Anti TNFs: positioning of other biologics for Crohn s disease Christina Ha, MD Cedars Sinai Inflammatory Bowel Disease Center Objectives: To define high and low risk patient and disease features
More informationVedolizumab: policing leukocyte traffic
Oxford Inflammatory Bowel Disease MasterClass Vedolizumab: policing leukocyte traffic Dr Brian Feagan, London, Canada Vedolizumab : Policing Lymphocyte Traficking Brian G. Feagan Professor of Medicine,
More informationPredicting response to anti - integrin therapy: long term efficacy and roles for optimisation with vedolizumab.
Predicting response to anti - integrin therapy: long term efficacy and roles for optimisation with vedolizumab. Dr Peter Irving Guy s and St Thomas Hospital, London King s College London Response to vedolizumab
More informationCROHN'S DISEASE/ULCERATIVE COLITIS TREATMENT ALGORITHM
CROHN'S DISEASE/ULCERATIVE COLITIS TREATMENT ALGORITHM Crohn's Disease Ulcerative Colitis Steroids x 2 No prior AZA/6-MP Biologic Agent AZA/6-MP STEP-UP MANAGEMENT APPROACH Advantages Patients attain remission
More informationNew treatment options in UC. Rob Bryant IBD Consultant Royal Adelaide Hospital
New treatment options in UC Rob Bryant IBD Consultant Royal Adelaide Hospital Talk Outline 1. Raising expectations 2. Optimising UC therapy 3. Clinical trials 4. What s new on the PBS? 5. Questions 1.
More informationAssociation Between Plasma Concentrations of Certolizumab Pegol and Endoscopic Outcomes of Patients With Crohn's Disease
Association Between Plasma Concentrations of Certolizumab Pegol and Endoscopic Outcomes of Patients With Crohn's Disease Jean Frédéric Colombel, William J. Sandborn, Matthieu Allez, Jean Louis Dupas, Olivier
More informationEfficacy and Safety of Treatment for Pediatric IBD
Efficacy and Safety of Treatment for Pediatric IBD Andrew B. Grossman MD Co-Director, Center for Pediatric Inflammatory Bowel Disease Assistant Professor of Clinical Pediatrics Division of Gastroenterology,
More informationSelection and use of the non-anti- TNF biological therapies: Who? When? How?
Selection and use of the non-anti- TNF biological therapies: Who? When? How? Asher Kornbluth, MD Clinical Professor of Medicine The Henry D. Janowitz Division of Gastroenterology The Icahn School of Medicine
More informationBiologics in 2016: How Do We Select the Most Appropriate Agent? Gary R. Lichtenstein, MD, FACG University of PA School of Medicine Philadelphia, PA
Biologics in 2016: How Do We Select the Most Appropriate Agent? Gary R. Lichtenstein, MD, FACG University of PA School of Medicine Philadelphia, PA Overview Indications and Drug Selection Contraindications
More informationOptimal Use of Immunomodulators and Biologics
3/17/214 Optimal Use of Immunomodulators and Biologics Edward V. Loftus, Jr., M.D. Professor of Medicine Division of Gastroenterology and Hepatology Mayo Clinic Rochester, Minnesota, U.S.A. Loftus Disclosures
More informationMedical Management of Inflammatory Bowel Disease
Medical Management of Inflammatory Bowel Disease John K. Marshall MD MSc FRCPC AGAF Division of Gastroenterology McMaster University John K. Marshall: Conflicts of Interest Speaker: AbbVie, Allergan, Ferring,
More informationProgress in Inflammatory Bowel Disease
Progress in Inflammatory Bowel Disease Gary R Lichtenstein, MD Director, Center for IBD University of Pennsylvania School of Medicine Hospital of the University of PA Philadelphia, PA Disclosure Research,
More informationTreating to Achieve a Target and Disease Monitoring in 2015: State of the Art
Treating to Achieve a Target and Disease Monitoring in 2015: State of the Art David T. Rubin, MD The Joseph B. Kirsner Professor of Medicine Chief, Section of Gastroenterology, Hepatology and Nutrition
More informationHow to Optimize Induction and Maintenance Responses: Definitions and Dosing Advances in Inflammatory Bowel Disease December 6, 2009
How to Optimize Induction and Maintenance Responses: Definitions and Dosing 2009 Advances in Inflammatory Bowel Disease December 6, 2009 Fernando Velayos MD MPH University of California, San Francisco
More informationAdvances in the development of new biologics in inflammatory bowel disease
INVITED REVIEW Annals of Gastroenterology (2016) 29, 1-6 Advances in the development of new biologics in inflammatory bowel disease Bella Ungar, Uri Kopylov Sheba Medical Center, Tel Hashomer and Sackler
More informationOptimizing the effectiveness of anti-tnf therapy in paediatric IBD
Optimizing the effectiveness of anti-tnf therapy in paediatric IBD Anne Griffiths MD, FRCPC Co-Lead, Inflammatory Bowel Disease Center Northbridge Chair in IBD Hospital for Sick Children, Professor of
More informationPersonalized Medicine in IBD: Where Are We in 2013
Personalized Medicine in IBD: Where Are We in 2013 David A. Schwartz, MD Director, Inflammatory Bowel Disease Center Associate Professor of Medicine Vanderbilt University Medical Center What is Personalized
More informationUlcerative colitis (UC) is a chronic inflammatory
Induction and Maintenance Therapy with Vedolizumab, a Novel Biologic Therapy for Ulcerative Colitis Feagan BG, Rutgeerts P, Sands BE, et al; GEMINI 1 Study Group. Vedolizumab as induction and maintenance
More informationAvailable Data on Pediatric Exposure Response a Clinician s Perspective
Available Data on Pediatric Exposure Response a Clinician s Perspective Marla Dubinsky, MD Professor of Pediatrics and Medicine Chief Pediatric GI and Nutrition Co-Director Susan and Leonard Feinstein
More informationGionata Fiorino VEDOLIZUMAB E IBD. Un nuovo target terapeutico
Gionata Fiorino VEDOLIZUMAB E IBD Un nuovo target terapeutico Anti cell adhesion molecules Danese S, NEJM 2011 6 Steps leukocyte recruitment Fiorino G. et al. 2010 Vedolizumab Blocks Fewer Biological Pathways
More informationAzathioprine for Induction and Maintenance of Remission in Crohn s Disease
Azathioprine for Induction and Maintenance of Remission in Crohn s Disease William J. Sandborn, MD Chief, Division of Gastroenterology Director, UCSD IBD Center Objectives Azathioprine as induction and
More informationOptimizing the treatment of IBD through use of therapeutic drug monitoring
Optimizing the treatment of IBD through use of therapeutic drug monitoring Adam S. Cheifetz Director, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center Associate Professor of
More informationPharmacy Management Drug Policy
SUBJECT: Multiple Sclerosis, Crohn s Disease POLICY NUMBER: PHARMACY-53 EFFECTIVE DATE: 4/08 LAST REVIEW DATE: 12/18/2018 If the member s subscriber contract excludes coverage for a specific service or
More information5/2/2018 SHOULD DEEP REMISSION BE A TREATMENT GOAL? YES! Disclosures: R. Balfour Sartor, MD
5/2/218 SHOULD DEEP REMISSION BE A TREATMENT GOAL? YES! Disclosures: R. Balfour Sartor, MD Grant support for preclinical studies: Janssen, Gusto Global, Vedanta, Artizan BALFOUR SARTOR, MD DISTINGUISHED
More informationChoosing and Positioning Biologic Therapy for Crohn s Disease: (Still) Looking for the Crystal Ball
Choosing and Positioning Biologic Therapy for Crohn s Disease: (Still) Looking for the Crystal Ball Siddharth Singh, MD, MS Assistant Professor of Medicine Division of Gastroenterology Division of Biomedical
More informationTherapeutic Drug Monitoring και ΙΦΝΕ το 2018
Therapeutic Drug Monitoring και ΙΦΝΕ το 2018 TDM: Ναι το χρειαζόμαστε, σε όλους και πάντοτε Κωνσταντίνος Κατσάνος Conflict of interest By means of this, the speaker confirms that he receives honoraria
More informationLong-term Efficacy of Vedolizumab for Crohn s Disease
Journal of Crohn's and Colitis, 217, 412 424 doi:1.193/ecco-jcc/jjw176 Advance Access publication September 28, 216 Original Article Original Article Long-term Efficacy of Vedolizumab for Crohn s Disease
More informationThe following slides are provided as presented by the author during the live educa7onal ac7vity and are intended for reference purposes only.
The following slides are provided as presented by the author during the live educa7onal ac7vity and are intended for reference purposes only. If you have any ques7ons, please contact Imedex via email at:
More informationEfficacy and Safety of Treatment for Pediatric IBD
Efficacy and Safety of Treatment for Pediatric IBD Andrew B. Grossman MD Co-Director, Center for Pediatric Inflammatory Bowel Disease Associate Professor of Clinical Pediatrics Division of Gastroenterology,
More informationLatest Treatment Updates for Crohn s Disease: Tailoring Therapy David G. Binion, M.D.
Latest Treatment Updates for Crohn s Disease: Tailoring Therapy David G. Binion, M.D. Co-Director, IBD Center Director, Nutrition Support Service UPMC Presbyterian Hospital Division of Gastroenterology,
More informationCrohn's Disease. The What, When, and Why of Treatment
Crohn's Disease The What, When, and Why of Treatment Gary R. Lichtenstein, MD, FACG Professor of Medicine Director, Inflammatory Bowel Disease Program University of Pennsylvania Philadelphia, PA In my
More informationBiologics, Novel Therapeutic Approaches in Inflammatory Bowel Diseases
Biologics, Novel Therapeutic Approaches in Inflammatory Bowel Diseases Walter Reinisch Univ-Klinik für Innere Medizin III Abt. Gastroenterologie & Hepatologie AKH Wien The Biologic s evolution From availabilitydriven
More informationLatest Meds Approved for IBD: What are they and how do they work?
Latest Meds Approved for IBD: What are they and how do they work? JAMES LORD, MD PHD BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON MEDICAL CENTER SEPT 30, 2018 Brief history of IBD Dr. Burrill Crohn JAMA
More informationSelby Inflamm Bowel Dis. 2008:14:
Medical Management of Inflammatory Bowel Disease Freddy Caldera D.O. Assistant Professor Division of Gastroenterology Objectives Discuss Crohn s disease and Ulcerative Colitis Discuss Medications for Inflammatory
More informationIl ruolo degli anticorpi anti farmaco nella pratica clinica
Il ruolo degli anticorpi anti farmaco nella pratica clinica Daniela Pugliese, MD IBD Unit Complesso Integrato Columbus Gemelli Hospital Catholic University Foundation, Rome - Italy Therapeutic Drug monitoring
More informationInitiation of Maintenance Treatment in Moderate to Severe New Onset Crohn s Disease
Initiation of Maintenance Treatment in Moderate to Severe New Onset Crohn s Disease The Case for Starting with Anti-TNFα Agents Maria Oliva-Hemker, M.D. Chief, Division of Pediatric Gastroenterology &
More informationTherapies for IBD: the Pipeline. New Therapeutic Agents in IBD
Therapies for IBD: the Pipeline New Therapeutic Agents in IBD William J. Sandborn, MD Professor & Chief, Division of Gastroenterology Director, UCSD IBD Center Budesonide Oral MMX budesonide Rectal budesonide
More informationAgenda. Predictive markers in IBD. Management of ulcerative colitis. Management of Crohn s disease
Agenda Predictive markers in IBD Management of ulcerative colitis Management of Crohn s disease 2 Patients With UC (%) Distribution of UC Disease Severity at Presentation 1 Fulminant disease (9%) 8 6 4
More informationCurrent and Emerging Biologics for Ulcerative Colitis
Gut and Liver, Vol. 9, No. 1, January 2015, pp. 18-27 Review Current and Emerging Biologics for Ulcerative Colitis Sung Chul Park* and Yoon Tae Jeen *Division of Gastroenterology and Hepatology, Department
More informationMucosal healing: does it really matter?
Oxford Inflammatory Bowel Disease MasterClass Mucosal healing: does it really matter? Professor Jean-Frédéric Colombel, New York, USA Oxford Inflammatory Bowel Disease MasterClass Mucosal healing: does
More informationCorporate Medical Policy
Corporate Medical Policy Measurement of Serum Antibodies to Infliximab, Adalimumab and File Name: Origination: Last CAP Review: Next CAP Review: Last Review: measurement_of_serum_antibodies_to_infliximab_and_adalimumab
More informationHow to use infliximab?
How to use infliximab? Séverine Vermeire, MD, PhD Division of Gastroenterology University Hospital Gasthuisberg Leuven The how to use infliximab rules Before starting IFX: try optimizing chances for response!
More informationModerately to severely active ulcerative colitis
Adalimumab in the Treatment of Moderate-to-Severe Ulcerative Colitis: ULTRA 2 Trial Results Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients
More informationBiologic therapy with antagonists to tumor necrosis factor
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8:696 702 Reinduction With Certolizumab Pegol in Patients With Relapsed Crohn s Disease: Results From the PRECiSE 4 Study WILLIAM J. SANDBORN,* STEFAN SCHREIBER,
More informationCrohn s
Crohn s Disease David T. Rubin, MD, AGAF Joseph B. Kirsner Professor of Medicine Chief, Section of Gastroenterology, Hepatology, and Nutrition Co-Director, Digestive Diseases Center @IBDMD Disclosures
More informationHow do I choose amongst medicines for inflammatory bowel disease. Maria T. Abreu, MD
How do I choose amongst medicines for inflammatory bowel disease Maria T. Abreu, MD Overview of IBD Pathogenesis Bacterial Products Moderately Acutely Inflamed Chronic Inflammation = IBD Normal Gut Mildly
More informationDrug Level Monitoring in IBD. Objectives
Drug Level Monitoring in IBD Corey A. Siegel, MD, MS Director, Dartmouth-Hitchcock IBD Center Associate Professor of Medicine, Geisel School of Medicine at Dartmouth Objectives Review non-biologic drug
More informationOptimizing Therapies for Severe Ulcerative Colitis October 19, 2014
Optimizing Therapies for Severe Ulcerative Colitis October 19, 2014 Ellen J. Scherl, MD, FACP, FACG, AGAF, FASGE, NYSGEF Director Jill Roberts Center for Inflammatory Bowel Disease Jill Roberts IBD Research
More informationSubmitted by xxxxxxxxxxxxxxxxx, xxxxxxxxx RCP and co-ordinated by xxxxxxxxxxxx, xxxxxxxxxxxxxxxxxxxxxxxxxxxxx, Royal Liverpool University Hospital.
Royal College of Physicians statement on the appraisal of use of tumour necrosis factor alpha (TNF-α) inhibitors (adalimumab, certolizumab pegol and infliximab) and natalizumab for Crohn's disease Submitted
More informationEffectiveness and safety of vedolizumab for treatment of Crohn s disease: a systematic review and meta-analysis
Systematic review/meta-analysis Effectiveness and safety of vedolizumab for treatment of Crohn s disease: a systematic review and meta-analysis Paweł Moćko 1, Paweł Kawalec 1, Beata Smela-Lipińska 1, Andrzej
More informationJoin the conversation at #GIFORUMCCFA
1 Join the conversation at #GIFORUMCCFA 2 Disclosures In accordance with the ACCME Standards for Commercial Support of CME, the speakers for this course have been asked to disclose to participants the
More informationPersonalized Medicine in IBD
Personalized Medicine in IBD Anita Afzali MD, MPH Assistant Professor of Medicine Director, Inflammatory Bowel Diseases Program University of Washington Harborview Medical Center CCFA April 2 nd, 2016
More informationOPTIMAL USE OF IMMUNOMODULATORS AND BIOLOGICS Edward V. Loftus, Jr., MD, FACG
1C: Advances in Inflammatory Bowel Disease OPTIMAL USE OF IMMUNOMODULATORS AND BIOLOGICS Edward V. Loftus, Jr., MD, FACG narrow interpretation of this presentation topic would A be a discussion of dosing
More informationTNF Inhibitors: Lessons From Immunogenicity
TNF Inhibitors: Lessons From Immunogenicity Edward Keystone, MD, FRCP(C) Professor of Medicine University of Toronto Toronto, Canada Edward Keystone, MD FRCP(C) Disclosures Sources of Funding for Research:
More informationAnti tumor necrosis factor (TNF) agents have
Achieving Clinical Response and Remission in Moderate-to-Severe Ulcerative Colitis With Golimumab Sandborn WJ, Feagan BG, Marano C, et al; PURSUIT-SC Study Group. Subcutaneous golimumab induces clinical
More informationTherapy for Inflammatory Bowel Disease
Therapy for Inflammatory Bowel Disease Jonathan P. Terdiman, MD Professor of Clinical Medicine Clinical Director, Center for Colitis and Crohn s Disease University of California San Francisco, CA UC: Current
More informationWHY HAVE WE NOT FINALLY FIGURED OUT COMBINATION THERAPY?
WHY HAVE WE NOT FINALLY FIGURED OUT COMBINATION THERAPY? Siew Ng, Professor MBBS, FRCP, (Lon, Edin), PhD (Lond), AGAF, FHKCP, FHKAM (medicine) Department of Medicine and Therapeutics Chinese University
More informationPersonalized Medicine. Selecting the Right First-line Biologic Agent. Gene Expression Profiles Crohn s Disease. The Right Treatment
Personalized Medicine Selecting the Right First-line Biologic Agent William Tremaine, M.D. Maxine and Jack Zarrow Professor Mayo Clinic Rochester, MN, USA The Right Treatment Pretreatment Genomic Analysis
More information2nd Nottingham IBD Masterclass, 2017
2nd Nottingham IBD Masterclass, 217 Positioning IL12/IL23 blockade in the Crohn s disease treatment algorithm Prof James Lindsay, Consultant Gastroenterologist, Barts Health NHS Trust Professor in Inflammatory
More informationPrimary Results Citation 2
Table S1. Adalimumab clinical trials 1 ClinicalTrials.gov Rheumatoid Arthritis 3 NCT00195663 Breedveld FC, Weisman MH, Kavanaugh AF, et al. The PREMIER study. A multicenter, randomized, double-blind clinical
More informationMEDICAL POLICY II. III. SUBJECT: MEASUREMENT OF SERUM ANTIBODIES TO INFLIXIMAB, ADALIMUMAB, AND VEDOLIZUMAB
MEDICAL POLICY SUBJECT: MEASUREMENT OF SERUM ANTIBODIES TO INFLIXIMAB, ADALIMUMAB, AND PAGE: 1 OF: 6 If a product excludes coverage for a service, it is not covered, and medical policy criteria do not
More informationMedical Therapy for Pediatric IBD: Efficacy and Safety
Medical Therapy for Pediatric IBD: Efficacy and Safety Betsy Maxwell, MD Assistant Professor of Clinical Pediatrics Division of Gastroenterology, Hepatology, and Nutrition Pediatric IBD: Defining Remission
More informationCrohn's Disease. The What, When, and Why of Treatment
Crohn's Disease The What, When, and Why of Treatment Francis A. Farraye, MD, MSc, FACG Professor of Medicine Clinical Director, Section of Gastroenterology Boston University School of Medicine Boston,
More informationLatest Treatment Updates for Ulcerative Colitis: Evolving Treatment Goals
Latest Treatment Updates for Ulcerative Colitis: Evolving Treatment Goals Stephen Hanauer, MD Professor of Medicine Medical Director, Digestive Disease Center Northwestern Medicine Chicago, Illinois Speaker
More informationIndications for use of Infliximab
Indications for use of Infliximab Moscow, June 10 th 2006 Prof. Dr. Dr. Gerhard Rogler Klinik und Poliklinik für Innere Medizin I Universität Regensburg Case report 1989: Diagnosis of Crohn s disease of
More informationWe are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists. International authors and editors
We are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists 4,100 116,000 120M Open access books available International authors and editors Downloads Our
More informationSYNOPSIS. Issue Date: 25 Oct 2011
SYNOPSIS Issue Date: 25 Oct 2011 Name of Sponsor/Company Name of Finished Product Name of Active Ingredient(s) Janssen Research & Development STELARA Ustekinumab Protocol No.: Title of Study: Study Name:
More informationOf Treatment For Inflammatory Bowel Diseases
Balancing The Risks And Benefits Of Treatment For Inflammatory Bowel Diseases Corey A. Siegel, MD Assistant Professor of Medicine Dartmouth Medical School Director, Inflammatory Bowel Diseases Center Dartmouth-Hitchcock
More informationThe future of IBD therapeutic research
The future of IBD therapeutic research Jean-Frederic Colombel, MD Director Susan and Leonard Feinstein IBD Clinical Center Icahn School of Medicine, Mount Sinai Hospital New York J-F Colombel has served
More informationCommon Questions in Crohn s Disease Therapy. Case
Common Questions in Crohn s Disease Therapy Jean-Paul Achkar, MD, FACG Kenneth Rainin Chair for IBD Research Cleveland Clinic Case 23 yo male with 1 year history of diarrhea, abdominal pain and 15 pound
More informationU of Cape Town, South Africa, 10 U of Washington, Seattle, WA,USA, 11 CHRU de Lille, Hôpital Claude Huriez, Lille, France, 12
A Multicenter, Double-blind, Placebo-controlled Phase 3 Study of Ustekinumab, a Human IL-12/23p40 Monoclonal Antibody, in Moderate-severe Crohn s Disease Refractory to Anti-TNFα: UNITI-1 WJ Sandborn 1,
More informationPerianal and Fistulizing Crohn s Disease: Tough Management Decisions. Jean-Paul Achkar, M.D. Kenneth Rainin Chair for IBD Research Cleveland Clinic
Perianal and Fistulizing Crohn s Disease: Tough Management Decisions Jean-Paul Achkar, M.D. Kenneth Rainin Chair for IBD Research Cleveland Clinic Talk Overview Background Assessment and Classification
More informationCrohn s disease is a chronic, progressive, and disabling
At a Glance Practical Implications p e136 Author Information p e140 Full text and PDF Web exclusive eappendix Real-World Anti-TNF Dose Escalation in Patients With Crohn s Disease Original Research David
More informationCCFA. Crohns Disease vs UC: What is the best treatment for me? November
CCFA Crohns Disease vs UC: What is the best treatment for me? November 8 2009 Ellen J. Scherl,, MD, FACP,AGAF Roberts Inflammatory Bowel Disease Center Weill Medical College Cornell University New York
More informationTreatment of ulcerative colitis with adalimumab or infliximab: long-term follow-up of a single-centre cohort
Alimentary Pharmacology and Therapeutics Treatment of ulcerative colitis with adalimumab or infliximab: long-term follow-up of a single-centre cohort N. Gies, K. I. Kroeker, K. Wong & R. N. Fedorak Division
More informationAnne Griffiths MD, FRCPC. SickKids Hospital, University of Toronto. Buenos Aires, August 16, 2014
Management and Medical Therapies for Crohn disease: strategies to enhance mucosal healing Anne Griffiths MD, FRCPC SickKids Hospital, University of Toronto Buenos Aires, August 16, 2014 New onset Crohn
More informationTumor necrosis factor-alpha antibody for maintenace of remission in Crohn s disease (Review)
Tumor necrosis factor-alpha antibody for maintenace of remission in Crohn s disease (Review) Behm BW, Bickston SJ This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration
More informationENTYVIO (VEDOLIZUMAB)
ENTYVIO (VEDOLIZUMAB) UnitedHealthcare Community Plan Medical Benefit Drug Policy Policy Number: CS2017D0053F Effective Date: July 1, 2017 Table of Contents Page INSTRUCTIONS FOR USE... 1 BENEFIT CONSIDERATIONS...
More information