New and Future Adhesion Molecule Based Therapies in IBD
|
|
- Reynold Wells
- 6 years ago
- Views:
Transcription
1 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
2 Mosli M et al, Drugs 2014; 74:
3 Consequences of Leukocyte Entry Cellular immunity Humoral immunity Cytokine/chemokine expression Phagocytic activity Antigen presentation Frohman EM, et al. J Clin Immunol. 1989;9:1-9.
4 Natalizumab: A Humanized Monoclonal Antibody Against α 4 -Integrins CDRs α 4 -Integrin antagonist CDR grafted from murine antibody Human IgG4 subclass framework Non-complement fixing Human IgG4 framework CDRs, complementarity-determining regions. Sheremata WA, et al. Neurology. 1999;52:
5 Cumulative Number of New Gd+ Lesions Miller et al., 2003 (1 Year) Mean no. of new Gd+ lesions Infusion given Placebo (n=71) 3 mg/kg (n=68) 6 mg/kg (n=74) Months 9.6 *P<0.001 vs placebo 1.1* 0.7* Miller DH, et al. N Engl J Med. 2003;348:15-23.
6 ENACT-2: Patients Removed from Concurrent Steroids 80 Patients not receiving steroids (%) % 64% 61% 54% 54% 34% Natalizumab 300 mg (n = 67) 64% 50% 58% * 34% 57% * 30% 55% * 25% 0 Placebo (n = 76) * P < Time (months) Start ENACT-2 Sandborn WJ. et al. (ENACT-2) N Engl J Med. 2005;353(18):
7 PML JCV- human papova virus Latent in renal tubuloepithelium; 60% of individuals Severe CNS disease in highly immunosuppressed patients (HIV/combination chemotherapy) Very high risk with natalizumab therapy (1:160 to 1:10,000 dependent on risk factors) chilling effect on anti-adhesion molecule Rx
8 Therapeutic Targets Leucocyte Adhesion CD 11a/CD18 NATALIZUMAB VEDOLIZUMAB LEUCOCYTE CCX282-B ISIS-2302 α4β1 (VLA-4) α4β7 CCR9 MAdCAM mab (PF ) rhumab Beta 7 CCL-25 ICAM-1 MadCAM-1 VCAM-1 Adapted from Danese S Gut 2011;60: ACTIVATED INTESTINAL MICROVASCULAR ENDOTHELIAL CELLS
9 Lobaton T et al AP&T 2014; 39:
10 Lobaton T et al AP&T 2014; 39:
11 Vedolizumab UC induction (GEMINI 1) Response, Remission, Mucosal Healing at 6 Weeks P< Induction ITT Population P= % P= % CI: Δ , 31.7 Δ , 18.3 Δ , 25.9 Feagan B et al NEJM 2013; 369:
12 Clinical Response and Remission at 6 Weeks: Prior Anti-TNFα Failure vs No Anti-TNFα Exposure ITT Population % Patients With Prior Anti-TNF Failure Patients Without Anti-TNF Exposure Placebo Vedolizumab Clinical Response Clinical Remission Clinical Response Clinical Remission % CI: 3.9, , , , 30.2 Feagan, B.G. et al New Eng J Med 2013
13 Etrolizumab: Clinical Remission in All Comers & by Anti-TNF status Primary endpoint at Week 10 95% CI (12,75) (-2,50) p-value Proportion of patients (%) Proportion of patients (%) Primary Endpoint 95% CI (12,30) (0.2,20) p-value % CI (-5.1,16.4) (-5.6,14.7) n=15 n=16 n=12 n=15 n=16 n=12 n=25 n=22 n=25 n=25 n=22 n=25 Vermeire S et al Lancet 2014, 384:309-18
14 Etrolizumab: Clinical Remission in All Comers & by Anti-TNF status Primary endpoint at Week 10 95% CI (12,75) (-2,50) p-value Proportion of patients (%) Proportion of patients (%) Primary Endpoint 95% CI (12,30) (0.2,20) p-value % CI (-5.1,16.4) (-5.6,14.7) n=15 n=16 n=12 n=15 n=16 n=12 n=25 n=22 n=25 n=25 n=22 n=25 Vermeire S et al Lancet 2014, 384:309-18
15 Etrolizumab: alphae as predictive marker for response? Real-Time qpcr Immunohistochemistry Vermeire S et al Lancet 2014, 384:309-18
16 Anti-MadCam in UC: Primary End Point: Clinical Remission at Week % mitt Population 20.0% Remission Rates 15.0% 11.3% * 16.7% * 15.5% * 10.0% 5.0% 2.7% 5.7% * p< % 0 mg 7.5 mg 22.5 mg 75 mg 225 mg Central Read Vermeire et al ECCO 2015 and Reinisch et al DDW 2015
17 Secondary Efficacy End Points: Clinical Remission in Anti-TNF Naïve vs Experienced Naïve Experienced 30.0% 30.0% 25.8%* 25.0% 25.0% 23.3% 20.0% 20.0% Central Read (mitt) 15.0% 10.0% 6.5% 16.7% 10.0% Central Read (mitt) 15.0% 10.0% 7.3% 9.8%* 9.8%* 5.0% 5.0% 2.5% 0.0% 0 mg 7.5 mg 22.5 mg 75 mg 225 mg Naïve * p<0.05 Dose 0.0% 0.0% 0 mg 7.5 mg 22.5 mg 75 mg 225 mg Experienced * p<0.05 Dose Odds of remission in naïve population is significantly higher (p<0.001) than experienced population ECCO 2015 and DDW
18 Cochrane: clinical remission induction UC Vedolizumab week 6 Etrolizumab week 10 Anti-MadCam week 12
19 Cochrane: endoscopic remission induction UC Vedo week 6 Etrolizumab week 10 Anti-MadCam week 12
20 Vedolizumab UC (GEMINI 1): Primary and Secondary Outcomes Through 52 Weeks Maintenance ITT Population *** *** *** *** *** *** *** * % ** ** Δ26.1 Δ29.1 Δ32.8 Δ28.5 Δ32.0 Δ36.3 Δ11.8 Δ15.3 Δ17.6 Δ31.4 n: *P<0.05 **P<0.01 ***P< Feagan B et al NEJM 2013; 369:
21 Cochrane: Maintenance of Remission Week 52 Vedolizumab - UC Clinical remission Endoscopic healing
22 Vedolizumab CD induction (GEMINI 2) Response and remission at 6 Weeks Primary: Clinical Remission CDAI 150 Primary: Enhanced Clinical Response (CDAI-100) Percent of Subjects p< (7.8) p= (5.7) N=148 Placebo 14.5 N=220 Vedolizumab 20 0 N=148 N=220 Placebo Vedolizumab Sandborn WJ, et al. NEJM 2013;369:
23 Vedolizumab Induction GEMINI-III in CD CDAI-100 Response ITT Population Patients, % Anti-TNFα Failure Population Overall Population (n=315) (n=416) PBO VDZ * Week 6 Week 10 Week 6 Week 10 CDAI-100 Response *P= vs placebo; P< vs placebo; P= vs placebo Sands et al,gastroenterology 2015
24 Anti-MadCam CD: Secondary Efficacy End Point Remission 40% 30% 29% 27% 27% 28% 29% 24% 23% 20% 17% 10% 0% Week 8 Week 12 Placebo *None of the doses were statistically significant compared to placebo at week 8 or week 12 D Haens et al ECCO 2015 and Sandborn W et al DDW
25 Anti-MadCam CD: Remission by Baseline CRP Quartiles Remission, CRP>7.5 (1st quartile) Remission, CRP>18 (median) 50% 50% 40% 40% 37%* 32% 30% 20% 27%* 24%* 24% 20% 28% 30% 20% 28%* 20% 23% 23% 22% 23% 20% 10% 10% 10% 6% 0% Week 8 Week 12 0% Week 8 Week 12 *P<0.05 Placebo *P=0.053 Placebo D Haens et al ECCO 2015 and Sandborn W et al DDW
26 Cochrane: Clinical remission induction CD Vedo week 6 Anti-MadCam week 12
27 Vedolizumab CD (GEMINI 2): Primary and Secondary Outcomes Through 52 Weeks Maintenance ITT Population Primary Outcome * ** Secondary Outcomes ** ** * * Patients, % Δ17.4 Δ14.7 Δ13.4 Δ15.3 Δ15.9 Δ12.9 Δ7.2 Δ2.0 *P<0.05 **P<0.01 CS tapering began in responders at 6 weeks; for others, as soon as a clinical response was achieved. Sandborn WJ, et al. NEJM 2013;369:
28 Cochrane: Maintenance of Remission Week 52 vedolizumab CD Clinical remission
29 Cochrane: Serious Adverse events Vedolizumab Etrolizumab Anti-MadCam
30 Poisson Probability Distribution of the Likelihood of Observing Cases of PML with Vedolizumab Colombel JF et al. Gastroenterology. Submitted.
31 S1P 1R Modulation Results in Sequestration of Lymphocytes in Lymph Nodes S1P 1R agonism induces receptor internalization on lymphocytes resulting in functional antagonism and loss of ability to respond to S1P gradient Lymphocytes become trapped in lymph nodes, reducing circulating lymphocyte counts Upon drug withdrawal receptor expression is restored and lymphocytes leave nodes reversing peripheral reduction
32 Fingolomod in MS P<0.001 Adjusted Annualized Relapse Rate Interferon (N=431) Cohen JA. et al. N Eng J Med 2010;362(5): Fingolimod 0.5 mg (N=429) Fingolimod 1.25 mg (N=420)
33 Ozanamod :Study Design Induction Period Maintenance Period 7-Day Dose Titration 8 Weeks Treatment Primary Endpoint: Induction 24 Weeks Treatment Week 32 Maintenance Endpoint Placebo (N=65) Randomization RPC mg (N=65) Mayo Responders RPC mg (N=67) Disease Relapse Open-Label
34 Sandborn et al DDW 2015 Pharmacodynamic Effect: Mean (SE) Percent Change in Absolute Lymphocyte Counts ~32% ~49%
35 1 Endpoint: Proportion of Patients in Remission at Week 8 (Adjudicated Central Read) Δ = 7.8% p = Δ = 10.8% p = Proportion of Patients in Remission Sandborn et al DDW 2015
36 Sandborn et al ECCO Endpoint: Proportion of Patients With Mucosal Improvement (Endoscopy score of 0-1 at Week 8, Adjudicated Central Read) Proportion of Patients With Mucosal Improvement Δ = 14.9% p = Δ = 22.6% p =
37 Sandborn et al DDW Endpoint: Proportion of Patients in Clinical Response at Week 8 (Adjudicated Central Read) Proportion of Patients in Clinical Response Δ = 16.1% p = Δ = 21.6% p =
38 Proportion of Patients in Remission Week 8 Week 32 Sandborn et al UEGW 2015
39 Proportion of Patients in Clinical Response Week 8 Week 32 * central read Sandborn et al UEGW 2015
40 Proportion of Patients With Mucosal Improvement/Healing (Endoscopy score of 1) Week 8 Week 32 Sandborn et al UEGW 2015
41 Safety: Treatment Emergent Adverse Events (TEAEs) Maintenance Period Number of Subjects Placebo (N=25) n (%) Ozanimod 0.5 mg (N=36) n (%) Ozanimod 1 mg (N=42) n (%) 1 TEAE 8 (32.0) 4 (11.1) 11 (26.2) Most Common TEAEs Placebo Ozanimod 0.5 mg Ozanimod 1 mg Ulcerative colitis flare 2 (8.0) 0 1 (2.4) Urinary Tract Infection 1 (4.0) 1 (2.8) 0 Serious TEAEs Placebo Ozanimod 0.5 mg Ozanimod 1 mg Number of Subjects with 1 Serious TEAE 2 (8.0) 0 1 (2.4) Anaemia haemolytic autoimmune 1 (4.0) 0 0 Colitis ulcerative 1 (4.0) 0 0 Herpes zoster 1 (4.0) 0 0 Colon adenoma (2.4)
42 Cardiac Safety Profile of RPC1063 Overall Incidence of Cardiac TEAEs SYSTEM ORGAN CLASS Preferred Term Placebo (N=65) RPC mg (N=65) RPC mg (N=67) CARDIAC DISORDERS 2 (3.1) 1 (1.5) 2 (3.0) Bradycardia* (3.0) First Degree AV Block** 0 1 (1.5) 0 Sinus Bradycardia** 0 1 (1.5) 0 Palpitations 2 (3.1) 0 0 * Day 1: Neither subject had HR < 45 bpm (bradycardia cutoff), with screening & pre-dose HR in the 50 s ** Day 8: HR=46, PR interval = 201 ms (ULN=200 ms) occurred in the same subject Day 1: Cardiac Findings on 24-hr Holter Monitoring Placebo (N=65) RPC mg (N=132) Subjects with 2 nd Degree AVB 0 0 Subjects with Sinus Pause 0 0 Sandborn et al ECCO 2015
43 Conclusions Monoclonal antibodies to integrins are effective for induction and maintenance of remission in UC and CD The safety profile of these agents is excellent but long term data are needed S1P1 agonists are oral agents that have demonstrated efficacy in both MS and UC Ozanomod is a promising new treatment for UC that is now being evaluated in Phase 3 studies Frohman EM, et al. J Clin Immunol. 1989;9:1-9.
Selective 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 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 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 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 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 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 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 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 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 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 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 informationSevere IBD: What to Do When Anti- TNFs Don t Work?
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
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 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 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 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 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 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 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 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 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 informationADHESION MOLECULES AS A THERAPEUTIC TARGET IN IBD
ADHESION MOLECULES AS A THERAPEUTIC TARGET IN IBD Raquel F. Leal, Azucena Salas Institut d investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Center Esther Koplowitz, Barcelona, Spain Disclosure: No
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 informationNew clinical study also provides data for Entyvio in inducing complete mucosal healing and endoscopic remission, particularly in bio-naïve patients
News Release Embargoed until February 16, 2018 at 17:00 CET Entyvio (vedolizumab) Shows Higher Rates of Mucosal Healing Versus TNFα-Antagonist Therapy in Ulcerative Colitis and Crohn s Disease Patients
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 informationNew and Emerging Therapies in IBD. Sarah Streett MD, AGAF Clinical Associate Professor of Medicine Stanford University
New and Emerging Therapies in IBD Sarah Streett MD, AGAF Clinical Associate Professor of Medicine Stanford University New and Emerging Therapies in IBD I have no relevant financial disclosures. IBD is
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 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 informationΑπό τη θεωρία στη πράξη: Συζήτηση κλινικών περιστατικών. Κωνσταντίνος Κατσάνος Επίκουρος Καθηγητής Γαστρεντερολογίας Πανεπιστήμιο Ιωαννίνων
Από τη θεωρία στη πράξη: Συζήτηση κλινικών περιστατικών Κωνσταντίνος Κατσάνος Επίκουρος Καθηγητής Γαστρεντερολογίας Πανεπιστήμιο Ιωαννίνων Conflict of interest By means of this, the speaker confirms that
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 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 informationThe 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 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 informationFuture Directions in IBD: Treatments & Approaches JAMES LORD, MD PHD BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON MEDICAL CENTER APRIL 29, 2018
Future Directions in IBD: Treatments & Approaches JAMES LORD, MD PHD BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON MEDICAL CENTER APRIL 29, 2018 Why do pharmaceuticals dominate IBD therapy discussions?
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 informationFuture Therapies in IBD. William J. Sandborn, M.D. Mayo Clinic, Rochester, Minnesota
Future Therapies in IBD William J. Sandborn, M.D. Mayo Clinic, Rochester, Minnesota Korzenik et al. Nature Reviews Drug Discovery 5, 197 209 (March 2006) doi:10.1038/nrd1986 Therapies for IBD: The Pipeline
More informationBiologics in Ulcerative Colitis. Chris Probert
Biologics in Ulcerative Colitis Chris Probert Why aren t there more trials of biologics in UC? perhaps because of ciclosporin therapy perhaps because of pouch surgery Similarities in treatment Many established
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 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 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 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 informationWithdrawal of drug therapy in patients with quiescent Crohn s disease
Withdrawal of drug therapy in patients with quiescent Crohn s disease DR. JEAN-FRÉDÉRIC COLOMBEL DIRECTOR OF THE IBD CENTER, ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI, NEW YORK, USA Withdrawal of drug therapy
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 informationCrohn's Disease. The What, When, and Why of Treatment
Crohn's Disease The What, When, and Why of Treatment Brian Feagan, MD, FACG Professor of Medicine and Epidemiology and Biostatistics Director, Robarts Clinical Trials Robarts Research Institute University
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 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 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 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 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 informationManagement of Moderate to Severe Ulcerative Colitis
Management of Moderate to Severe Ulcerative Colitis Neilanjan Nandi, MD Assistant Professor of Medicine Associate Program Director Division of Gastroenterology Drexel University College of Medicine Hahnemann
More informationUNC INFLAMMATORY BOWEL DISEASE DRUG PROTOCOL VEDOLIZUMAB (ENTYVIO)
UNC INFLAMMATORY BOWEL DISEASE DRUG PROTOCOL VEDOLIZUMAB (ENTYVIO) TREATMENT PROTOCOL: Vedolizumab is a humanized immunoglobulin G1 monoclonal antibody that targets 41 integrin and blocks its interaction
More information1. Comparative effectiveness of vedolizumab
Cost-effectiveness of vedolizumab (Entyvio ) for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were
More informationAchieving Success in Ulcerative Colitis: the Role of Infliximab
Achieving Success in Ulcerative Colitis: the Role of Infliximab Dr Gill Watermeyer IBD clinic Groote Schuur Hospital 17 th August 2012 Inflammatory Bowel Disease Crohn s disease and ulcerative colitis
More informationFOR UK NURSING MEDIA Embargoed until: 00:01 GMT, Friday 13 March 2015
Contact: Ross Selby Takeda UK Ltd Email ross.selby@takeda.com News Release FOR UK NURSING MEDIA Embargoed until: 00:01 GMT, Friday 13 March 2015 World s first gut-selective treatment for ulcerative colitis
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 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 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 informationPositioning Biologics in Ulcerative Colitis
Positioning Biologics in Ulcerative Colitis Bruce E. Sands, MD, MS Acting Chief, Gastrointestinal Unit Massachusetts General Hospital Associate Professor of Medicine Harvard Medical School Sequential Therapies
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 informationAAPS NBC 2016 IBD Symposium
AAPS NBC 2016 IBD Symposium Steven W Martin, PhD Group,, Pfizer, Cambridge, MA MAdCAM plays a central role in lymphocyte homing to the gut Adapted from Cheroutre and Madakamutil 2004 Anti-MAdCAM Mechanistic
More informationA Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Vedolizumab
Clin Pharmacokinet (2017) 56:1287 1301 DOI 10.1007/s40262-017-0546-0 REVIEW ARTICLE A Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Vedolizumab Maria Rosario 1 Nathanael
More informationResearch Update: Looking for the Answers
Research Update: Looking for the Answers Ted Denson, M.D. Schubert-Martin Inflammatory Bowel Disease Center Research Support: NIH/NIDDK, CCFA, BMRP Figure 2 Approach to Improve Outcomes for our IBD Patients
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 informationCAG Symposium: Management of IBD in 2018
CAG Symposium: Management of IBD in 2018 Waqqas Afif, MD, M. Sc., FRCPC, Associate Professor, Department of Medicine Division of Gastroenterology McGill University Health Center X X X X X CanMEDS Roles
More informationInflammatory bowel disease: Novel therpaies NZ November 2018
Inflammatory bowel disease: Novel therpaies NZ November 2018 Dr Charlie Lees Consultant Gastroenterologist From the Edinburgh IBD Unit at the Western General Hospital History of treatment for IBD 1950s
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 informationTreatment Goals. Current Therapeutic Pyramids Crohn s Disease Ulcerative Colitis 11/14/10
Current Management of IBD: From Conventional Agents to Biologics Stephen B. Hanauer, M.D. University of Chicago Treatment Goals Induce and maintain response/ remission Prevent complications Improve quality
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 informationMucosal Healing in Crohn s Disease. Geert D Haens MD, PhD University Hospital Gasthuisberg University of Leuven Leuven, Belgium
Mucosal Healing in Crohn s Disease Geert D Haens MD, PhD University Hospital Gasthuisberg University of Leuven Leuven, Belgium Mucosal Lesions in CD: General Features CD can affect the entire GI tract
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 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 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 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 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 informationOzanimod Induction and Maintenance Treatment for Ulcerative Colitis
The new england journal of medicine Original Article Induction and Maintenance Treatment for Ulcerative Colitis William J. Sandborn, M.D., Brian G. Feagan, M.D., Douglas C. Wolf, M.D., Geert D Haens, M.D.,
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 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 informationHighlights of DDW 2015: Crohn s disease
Highlights of DDW 2015: Crohn s disease Mark S. Silverberg, MD, PhD, FRCPC Associate Professor of Medicine, University of Toronto Staff Gastroenterologist, Mount Sinai Hospital Senior Investigator, Lunenfeld-Tanenbaum
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 informationPharmacotherapy of Inflammatory Bowel Disorder
PHARMACY / MEDICAL POLICY 5.01.563 Pharmacotherapy of Inflammatory Bowel Disorder Effective Date: Feb. 14, 2018 Last Revised: April 1, 2018 Replaces: Extracted from 5.01.550 RELATED MEDICAL POLICIES: 11.01.523
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 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 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 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 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 informationClinical Policy: Vedolizumab (Entyvio) Reference Number: CP.PHAR.265
Clinical Policy: (Entyvio) Reference Number: CP.PHAR.265 Effective Date: 07/16 Last Review Date: 07/17 Coding Implications Revision Log See Important Reminder at the end of this policy for important regulatory
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 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 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 informationPharmacotherapy of Inflammatory Bowel Disorder
PHARMACY / MEDICAL POLICY 5.01.563 Pharmacotherapy of Inflammatory Bowel Disorder Effective Date: June 9, 2019* Last Revised: Feb. 12, 2019 Replaces: Extracted from 5.01.550 RELATED MEDICAL POLICIES: 11.01.523
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 informationOnce Daily Dosing for Induction and Maintenance of Remission in Ulcerative Colitis
Once Daily Dosing for Induction and Maintenance of Remission in Ulcerative Colitis John K. Marshall MD MSc FRCPC AGAF Division of Gastroenterology McMaster University JKM 2014 Svartz N. Acta Med Scand
More informationCADTH CANADIAN DRUG EXPERT COMMITTEE FINAL RECOMMENDATION
CADTH CANADIAN DRUG EXPERT COMMITTEE FINAL RECOMMENDATION VEDOLIZUMAB (Entyvio Takeda Canada Inc.) Indication: Crohn s Disease Recommendation: The CADTH Canadian Drug Expert Committee (CDEC) recommends
More informationUlcerative Colitis: Refining our Management and Incorporating Newer Concepts
Ulcerative Colitis: Refining our Management and Incorporating Newer Concepts Asher Kornbluth, MD Clinical Professor of Medicine The Henry D. Janowitz The Mt. Sinai School of Medicine Refining our Management
More informationGenetics. Environment. You Are Only 10% Human. Pathogenesis of IBD. Advances in the Pathogenesis of IBD: Genetics Leads to Function IBD
Advances in the Pathogenesis of IBD: Genetics Leads to Function Pathogenesis of IBD Environmental Factors Microbes Scott Plevy, MD Associate Professor of Medicine, Microbiology & Immunology UNC School
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 informationvedolizumab 300mg powder for concentrate for solution for infusion (Entyvio ) SMC No. (1064/15) Takeda UK Ltd
vedolizumab 300mg powder for concentrate for solution for infusion (Entyvio ) SMC No. (1064/15) Takeda UK Ltd 05 June 2015 The Scottish Medicines Consortium (SMC) has completed its assessment of the above
More informationTitle: Author: Journal:
IMPORTANT COPYRIGHT NOTICE: This electronic article is provided to you by courtesy of Ferring Pharmaceuticals. The document is provided for personal usage only. Further reproduction and/or distribution
More informationSUPPLEMENTAL MATERIALS
SUPPLEMENTAL MATERIALS Intensity of Adverse Events The intensity for each adverse (AE) was defined by the study investigator as mild, moderate, or severe according to the following criteria: Mild: Awareness
More information