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Download case studies - Advances in Inflammatory Bowel Diseases
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2014 Advances in Inflammatory Bowel Diseases Management of Reactions To Immunomodulators and Biologics: Case Studies Orlando, Florida December 6, 2014 Robert Burakoff, MD MPH Clinical Chief, Division of Gastroenterology Director, Center for Digestive Health Associate Professor of Medicine Harvard Medical School Brigham and Women’s Hospital Case Study HPI: • CR 47 year old male diagnosed with left-sided colitis 8/01 • Did not respond to oral and enema 5ASA and required a course of corticosteroids • 11/05: started 6 MP • therapeutic dose of 6MP was 150 mg + 4 gm 5ASA Case Study • Occasional mild flares requiring cortenemas over the next 5 years • 10/12: Severe flare requiring corticosteroids documented by colonoscopy involving left colon • 11/12: Started adalimumab • Clinical remission achieved within 8 weeks Case Study • Over the next 2 years remains in complete clinical remission on 150 mg 6mp + 40 mg adalimumab qow • 5/14: Visits hand surgeon for a hx of right nail bed injury occurred 5 years ago • Seen by dermatologists- no cancer or fungus • Undergoes nail ablation and full thickness skin grafting Case Study • 7/14: Pathology reveals invasive squamous cell carcinoma • 9/14: A local resection was performed with clear margins Photograph Case Study • 10/14: Remains in complete clinical remission past 2 years on 150 mg 6mp and 40 mg adalimumab qow • Colonoscopy and biopsies reveal normal mucosa except mild activity in the rectum What would you do? • Stop 6mp? • Yes or no? • And why? Appropriate Use of Thiopurines • Measure TPMT before starting therapy • Closely monitor CBCs frequently in the first 8 weeks of therapy, less closely thereafter • Consider dose optimization strategies in selected populations • Recommend use of sunscreen and hats • Regular dermatology exams • Counsel about risk of lymphoma, but no proven strategies to reduce this risk • Avoid combination therapy in specific patient subsets 9 Azathioprine/6-Mercaptopurine Toxicity • • • • • • • Nausea Allergic reactions (fevers, arthralgias) Pancreatitis Bone marrow depression Drug-induced hepatitis Infectious complications Lymphoma Present DH, et al. N Engl J Med. 1980;302(18):981-7. 10 Drug Interactions with AZA/6-MP: 5-ASA AZA and 6-MP may interact with 5-ASAs, potentially causing leukopenia – 5-ASA reversibly inhibits TPMT – Low levels of TPMT causes accumulation 6-TGN, active metabolite – Increased 6-TGN associated with a decrease in WBC – Patients with low baseline levels of TPMT who are taking a combination of AZA/6-MP and 5-ASAs are at risk of clinically significant leukopenia Lowry PW, et al. Gut. 2001;49(5):656-64. 11 Non Melanoma Skin Cancer In Immunosuppressed IBD Patients • Non-melanoma skin cancer 65-250 times more frequent in immunosuppressed patient • Increased risk of melanoma and nonmelanoma skin cancer in IBD patients on immunosuppressive drugs • Educate patient on increased risk and sun protection strategies • Consider yearly dermatologic evaluation in patients on immunosuppressive agents Long MD, et al. Clin Gastroenterol Hepatol. 2010;8:268-274. Long MD, et al. Gastroenterology. 2012;143(2):390-399. 12 Thiopurines and Skin Cancer NMSC MELANOMA 12 10 8 7.06 6 4 2 1.85 2.17 1.1 1.03 0 Long MD, et al. Gastroenterology. 2012:143:390-399. Singh H, et al. Gastroenterology. 2011:141:1612-1620. Peyrin-Biroulet L, et al. Gastroenterology. 2011:141:1621-1628. Peyrin-Biroulet L, et al. Am J Gastroenterol. 2012;107(9):1443-1444. 13 Timing of Thiopurines and NMSC CESAME 12 SIR and 95% CI 10 8 6 4 2 0 Current Thiopurine Former Thiopurine Peyrin-Biroulet L, et al. Gastroenterology. 2011:141:1621-1628. Never Thiopurine 14 Minimizing Toxicity from Thiopurines • Check TPMT to guide dosing and avoid use of 6MP/AZA in patients with absent enzyme activity • Schedule regular CBC, liver enzymes • Educate patient on symptoms to watch for • Dosing at night anecdotally alleviates some complaints of nausea • Vaccinate patients for age-appropriate diseases prior to initiation Kane S. Curr Gastroenterol Rep. 2010;12(6):502-6. 15 Methotrexate Toxicity • • • • • • • • Rash Nausea, mucositis, diarrhea Bone marrow suppression Hypersensitivity pneumonitis Increased liver enzymes Hepatic fibrosis/cirrhosis Known abortifacient No documented increased risk of lymphoma or skin cancer Alfadhli A. Cochrane Database Syst Rev. 2005; 25(1):CD000459. 16 Minimizing Methotrexate Toxicity • • • • Regular counseling regarding birth control 1 mg folic acid supplementation daily Monitor CBC, liver enzymes every 6 weeks Evaluate risk factors for liver disease – Diabetes – Obesity – Alcohol abuse • Routine dose based liver biopsy no longer recommended Alfadhli A. Cochrane Database Syst Rev. 2005; 25(1):CD000459. 17
