Azathioprine for IBD : Better the devil you know Jeremy D. Sanderson.

Slides:



Advertisements
Similar presentations
Who should receive early anti-TNF therapy: With what benefits and risks? Ted Denson, MD Cincinnati Childrens Hospital Medical Center University of Cincinnati.
Advertisements

Medical Management of Ulcerative Colitis
Methotrexate Indications and Approaches
CZ5225 Methods in Computational Biology Lecture 9: Pharmacogenetics and individual variation of drug response CZ5225 Methods in Computational Biology.
Monotherapy using 6-MP or azathioprine for Crohn’s disease is dead: out with the old and in with the new Stephen B. Hanauer, MD Professor of Medicine Clinical.
Immunomodulators and Biologics Maria T. Abreu, MD University of Miami Miller School of Medicine Miami, Florida.
Thomas Ullman, M.D. Chief Medical Officer
Colitis in the Very Young
Management of Inflammatory bowel disease 8/12/10.
Rochester, Minnesota, USA
Miguel Regueiro, M.D. Professor of Medicine
Thiopurines still have a role in the management of pediatric IBD Athos Bousvaros MD, MPH Associate Director, IBD program Boston Children’s Hospital.
Emerging treatments in Crohn’s disease and ulcerative colitis
6-MP and AZA Applications and Approaches
Presented at the Arthritis Advisory Committee on July 15, 2003 by Naomi Winick, M.D.
Therapy of Inflammatory Bowel Diseases 2013 Gastroenterology Department Division of Medicine Eran Israeli MD.
Immunosuppressive Medications and IBD: Now and What’s Next
Treatment of Vasculitis: immunesuppressives and biologics
When can we use combination therapy for our pediatric IBD patients? Athos Bousvaros MD, MPH Advances in IBD Dec 2014.
Hepatitis web study Hepatitis web study Sofosbuvir in Genotypes 2 or 3 VALENCE Trial Phase 3 Treatment Naïve and Treatment Experienced Zeuzem S, et al.
Overview Diagnosis & Treatment
Asymptomatic UC patients on an immunomodulator with persistent moderate mucosal inflammation should either add a biologic or switch to a biologic William.
Recent advances in medical treatment of inflammatory bowel disease Adrian Thomas, Booth Hall Childrens Hospital Manchester, M9 7AA, UK.
Inflammatory Bowel Disease Kimberly Persley, MD Digestive Disease Associates of Dallas Presbyterian Hospital of Dallas.
Inflammatory Bowel Disease Treatment. Epidemiology Clinical Laboratory Imaging Pathology Response to treatment IBD.
Case Study Advances 2014 Betty White C-NP
Therapeutic algorithms for Crohn’s disease: Where are we in 2012?
Hepatitis web study Hepatitis web study Boceprevir in Treatment Experienced RESPOND-2 Phase 3 Treatment Experienced Bacon BR, et al. N Engl J Med. 2011;364:
Medical Management of Ulcerative Colitis Conrad Beckett Bradford Royal Infirmary M62 Course March 2006.
1 Unconventiional Therapies: What to do when all else fails? Scott Plevy, MD Associate Professor of Medicine, Microbiology & Immunology UNC School of Medicine.
1 Benefit-Risk of Crohn’s Disease Therapeutics William Sandborn, MD Mayo Clinic and Mayo College of Medicine Rochester, MN, USA.
“Antibiotics and corticosteroids: Indications and approaches”
Aminosalicylates in IBD: New Data on an Old Therapy Joel R. Rosh, MD Director, Pediatric Gastroenterology Goryeb Children’s Hospital/Atlantic Health Professor.
Vedolizumab in Pediatric IBD: We are Ready to Use It
Clinical Vignette: Medical Grand Rounds Joshua L. Denson MD Internal Medicine PGY2 January 7, 2013 U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS.
IBD Cases Stephen B. Hanauer, MD Professor of Medicine Feinberg School of Medicine Medical Director, Digestive Health Center.
You Can Never Stop a Biologic
Natalizumab- Unmet Need in the Management of Crohn’s Disease Doug Wolf, M.D. Atlanta Gastroenterology Associates July 31, 2007.
Should we change how we position biologics in ulcerative colitis? Bruce E. Sands, MD, MS Chief of the Dr. Henry D. Janowitz Division of Gastroenterology.
Pharmacogenetics (PGx) of Irinotecan: Scientific and Clinical Impact of UGT Polymorphism: Background Clinical Pharmacology Subcommittee of ACPS November.
Early Administration of Azathioprine Versus Conventional Management of Crohn’s Disease : A Randomized Controlled Trial F1. Ja Won Koo JACQUES COSNES, ANNE.
Am J Gastroenterol 2010; 105:1820–1829 F1 박재현. Background Background A novel mouse line with defects in both transforming growth factor- β type II receptor.
Improving outcome of Inflammatory Bowel Disease in children Dinesh Pashankar, MD Pediatric Gastroenterologist Director- Pediatric IBD program Yale University.
Dr Gill Watermeyer IBD Clinic Division of Gastroenterology
6-Thioguanosine Diphosphate and Triphosphate Levels in Red Blood Cells and Response to Azathioprine Therapy in Crohn’s Disease  Markus F. Neurath, Ralf.
IMMUNOSUPPRESSANTS AZATHIOPRINE.
P0866 Combination of Low dose Thiopurine and Allopurinol in patients with ulcerative colitis Please export the Keynote document as a PDF (File – Save as.
Azathioprine (AZA) Helen Liu Teagan Rolf von den Baumen
Volume 118, Issue 6, Pages (June 2000)
Goede V et al. Proc ASH 2014;Abstract 3327.
CASE DISCUSSION: Crohn's disease patient with bad perianal disease- are new therapies any help? Alana Wichmann, APN, MSN, FNP, Advanced Practice Nurse,
IBD: GC, purine analogs and MTX
Volume 118, Issue 6, Pages (June 2000)
6-Thioguanosine Diphosphate and Triphosphate Levels in Red Blood Cells and Response to Azathioprine Therapy in Crohn’s Disease  Markus F. Neurath, Ralf.
Methotrexate for Ulcerative Colitis: To Use or Not to Use?
Population Health Management for Inflammatory Bowel Disease
The pathway for commencement of thiopurines and monitoring.
Thiopurine Dose in Intermediate and Normal Metabolizers of Thiopurine Methyltransferase May Differ Three-Fold  Sharon J. Gardiner, Richard B. Gearry,
Clinical relevance of advances in genetics and pharmacogenetics of IBD
Corticosteroids in the ICU
Volume 118, Issue 4, Pages (April 2000)
Azathioprine metabolism.
Prevention of Postoperative Recurrence in Crohn's Disease
Initiating Azathioprine for Crohn's Disease
Phase III randomized controlled trial to compare biosimilar infliximab (CT-P13) with innovator infliximab in patients with active Crohn’s disease: 1-year.
Marla C. Dubinsky  Clinical Gastroenterology and Hepatology 
Presentation data from US VICTORY Consortium
Crohn’s Disease Biologic Pathway
Azathioprine metabolism.
Treatment Advances for RA
Presentation transcript:

Azathioprine for IBD : Better the devil you know Jeremy D. Sanderson

Azathioprine for inducing remission in active IBD 425 patients (209 AZA/6-MP, 216 placebo) End-points: steroid sparing effect, clinical response Overall response Aza/6-MP54% (CI 47%-61%) placebo 33% (CI 27%-40%) Pooled OR2.36 (CI 1.57 – 3.53) Time to respondPresent 1980av. 3.1 months OR 1.54 if <17 weeks Rx OR 2.51 if >17 weeks Rx Steroid sparingAza/6-MP65% (CI 56%-74%) placebo36% (CI 27%-45%) Pooled OR3.86 (CI 2.14 – 6.96) Sandborn et al, Cochrane Library, Issue 4, 2000

Background Azathioprine effective in 70% patients with IBD 30% failure due to:Intolerance 15% No response 15% IntoleranceBone marrow suppression Nausea Myalgia, flu-like symptoms Pancreatitis Hepatotoxicity Other Azathioprine failuresMTX, anti-TNF  Surgery

Azathioprine 6-Mercaptopurine 6-thioinosine nucleotide 6-thioguanine nucleotides Thiouric acid 6-Me MP TPMT*** Xanthine oxidase HGPRT IMPDH ImmunosppressionClinical benefit

Intermediate High (Normal) Very High Low

TPMT (thiopurine methyl transferase) allelic polymorphism High TPMT 89% Intermediate TPMT 11% Low TPMT 1/300 ?very high TPMT Severe Bone Marrow Suppression !! High risk of marrow suppression Low risk ? poor responders - + clinical response

Initiate at 100mg Build to 2mg/kg AZA treatment ? Check TPMT Enzyme / genotype Check TPMT Enzyme / genotype Homozygous deficient Heterozygous deficient Normal Initiate at 25mg Build to 1mg/kg Consider 2.5 – 5mg AZA ? Thioguanine Alternative Rx Consider 2.5 – 5mg AZA ? Thioguanine Alternative Rx TolerantIntolerant Very high Flu-like illness Pancreatitis Hepatitis Flu-like illness Pancreatitis Hepatitis Nausea Reduce dose Switch to 6-MP Alternative Rx ? Thioguanine Marrow suppression Reduce dose Check for drugs, 5’-nucleotidase def Parvovirus infection Repeat TPMT 6mo – 1yr. InducedNo change Increase AZAContinue Initiate at 100mg Build to 2.5 – 3mg/kg Non-response…...

Bargain Azathioprine …….. still the best and getting better

IBD medical therapy …… …… the Bridge approach

Crohn’s disease : the Bridge approach Antibiotics Nutritional Rx Steroids Methotrexate Anti-TNF  Azathioprine Mycophenolate ?? Methotrexate

Conclusions Many new and potentially exciting therapies for refractory IBD But before you use them …….. Make sure you get the best out of existing approaches