1. Treatment of Extra-intestinal Manifestations of IBD: Case studies Alan C. Moss MD, FEBG, FACG Associate Professor of Medicine Director of Translational Research

2. Case A. - 42 yr old male patient Left-sided ulcerative colitis for 4 years In clinical remission on mesalamine 4.8g/day Admitted for flare-up January 2013 – Rx IV steroids and discharged on PO prednisone taper Clinic follow-up – slow to taper off prednisone, azathioprine added, tolerated well Seen in office visit complaining of fatigue; started on oral ferrous sulfate 100mg by primary care physician

3. Trend in Hematologic Indices Hematocrit (40-50%) Iron Profile

4. What would you do next? A.Increase oral iron dose B.Blood transfusion C.Iron infusion D.Erythropoietin E.All of the above

5. Causes of Anemia in IBD Iron Deficiency Chronic Disease Bone marrow suppression Drug-induced hemolysis Vitamin B12 / folic acid deficiency Gisbert J, Am J Gastroenterol. 2008 May;103(5):1299-307. 20% of Out-patients 60% of Hospitalized patients

6. Determining Iron Deficiency in IBD Gasche C, Inflamm Bowel Dis 2007;13:1545-1553

7. Oral OR IV Iron for Iron Deficiency in IBD StudyComparisons Reinisch 2013PO FeSO4 200mg v IV iron isomaltoside Schroder 2005PO FeSO4 200mg v IV iron sucrose Gisbert 2009PO FeSO4 v IV iron sucrose Lindgren S 2009PO FeSO4 v IV iron sucrose Kulnigg 2008PO FeSO4 200mg v IV ferric carboxymaltose

8. Meta-Analysis of Trials to Date Hb rise >2g/dl - RR of 0.98, 95% (CI 0.9, 1.1) p=0.7 Mean change in Hb (g/dl) - 0.7 96% (CI 0.3, 1.7) p=0.1 Increase in serum ferritin - 84, 95% (CI 79, 92) p>0.001 Risk of withdrawal due to adverse events RR 2.7 (CI 1.4, 5.2) p=0.002 Abhyankar, Moss submitted to DDW 2014

9. Erythropoietin for Anemia in IBD Schreiber s N Engl J Med. 1996 Mar 7;334(10):619-23

10. Guidelines – ECCO 2013 “Iron supplementation should be initiated when iron deficiency anemia is present, and considered when there is iron deficiency without anemia Intravenous iron is more effective and better tolerated than oral iron supplements Absolute indications for intravenous iron include severe anemia (hemoglobin < 10.0 g/dL), and intolerance or inadequate response to oral iron Intravenous iron should be considered in combination with an erythropoietic agent in selected cases where a rapid response is required” Van Asche G, J Crohns Colitis. 2013 Feb;7(1):1-33

11. Case B. - 59 year old male Colonic Crohn’s for 20 years Developed lymphoma while on azathioprine Recent flare-up; 4-6 BM per day, cramps Rx budesonide & metronidazole Call from PCP – in local ED with frank rectal bleeding, and swollen left leg Ultrasound – left leg Deep Venous Thrombosis (DVT)

12. Sigmoidoscopy

13. What would you suggest next? A.Low Molecular Weight Heparin B.Unfractionated Heparin C.Vena caval filter D.Other

14. Venous Thromboembolism in IBD – A ‘Preventable Complication’ 1-2% of all IBD hospitalizations Out-patients have 8-fold higher risk of VTE during flares, than when in remission Risks: age, UC, surgery, smoking, oral contraceptives Less than 40% of GIs ‘always’ prescribe VTE prophylaxis Nyugen G. Am J Gastroenterol. 2008 Sep;103(9):2272-80; Grainge MJ, Lancet. 2010 Feb 20;375(9715):657-63 Razik R, Can J Gastroenterol. 2012 Nov;26(11):795-8

15. VTE Prophylaxis is Under-Utilized in IBD Pleet J et al, DDW 2013, S434 Number of hospital days with VTE prophylaxis ordered ‘None’ ‘All’ Actual administration of ordered doses by nurses

16. VTE Prevention in IBD AGA Physician Performance Measures Set 2011; ‘Measure # 9: Patients with IBD receive prophylaxis for venous thromboembolism during hospitalization for any reason.’ LMW / UF heparin Compression stockings Minimizing IV catheter use Address smoking, OCP use, immobility ?Out-patient flares also