Treatment of Extra-intestinal Manifestations of IBD: Case studies

Alan C. Moss MD, FEBG, FACG

Associate Professor of MedicineDirector of Translational Research

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

Trend in Hematologic Indices

Hematocrit (40-50%) Iron Profile

What would you do next?

A. Increase oral iron dose

B. Blood transfusion

C. Iron infusion

D. Erythropoietin

E. All of the above

Causes of Anemia in IBD

Iron Deficiency Chronic

Disease

Bone marrow suppressionDrug-induced hemolysis

Vitamin B12 / folic acid deficiency

Gisbert J, Am J Gastroenterol. 2008 May;103(5):1299-307.

20% of Out-patients60% of Hospitalized patients

Determining Iron Deficiency in IBD

Gasche C, Inflamm Bowel Dis 2007;13:1545-1553

Oral OR IV Iron for Iron Deficiency in IBD

Study Comparisons

Reinisch 2013 PO FeSO4 200mg v IV iron isomaltoside

Schroder 2005 PO FeSO4 200mg v IV iron sucrose

Gisbert 2009 PO FeSO4 v IV iron sucrose

Lindgren S 2009 PO FeSO4 v IV iron sucrose

Kulnigg 2008 PO FeSO4 200mg v IV ferric carboxymaltose

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

Erythropoietin for Anemia in IBD

Schreiber s N Engl J Med. 1996 Mar 7;334(10):619-23

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

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)

Sigmoidoscopy

What would you suggest next?

A. Low Molecular Weight Heparin

B. Unfractionated Heparin

C. Vena caval filter

D. Other

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

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

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