1. TWH LIVER CENTRE UHN centre of excellence A case study: Hepatitis C treatment and severe anemia Colina Yim RN(EC), MN Nurse Practitioner CAHN 2013

2. TWH LIVER CENTRE Objective To illustrate the change of best practices in managing hepatitis C treatment related anemia To illustrate the change of best practices in managing hepatitis C treatment related anemia

3. TWH LIVER CENTRE Mr. Number 1 55 year old man first seen 2009 HCV G1, VL 1.30 x10E6 IU/mL Cryoglobulins 2%: leg numbness, leg rash Stopped alcohol age 53 No co-morbidities Liver biopsy: A3 F3-4 Treated 2008 PegIFNα2a 180mcg/ RBV 1200 mg/day HCVRNA negative at wk 12 Stopped after 29 wks: anemia, neutropenia Relapsed !

4. TWH LIVER CENTRE Mr. Number 1 2009 Treatment # 2 PegIFNα2a 180mcg/wk + RBV 1200 mg/day What to do ? Treat again ?

5. TWH LIVER CENTRE Treatment # 2 WeekHCV RNAALTASTHgbLkcANCPlts 01.04 E51882121364.63.1288 21.20 E5781091112.21.4176 44.52 E446721021.40.877 88.51 E22855931.70.9221 124.52 E12352871.61.196 16< 152859901.30.757

6. TWH LIVER CENTRE Treatment # 2 WeekHCV RNAALTASTHgbLkcANCPlts 01.04 E51882121364.63.1288 21.20 E5781091112.21.4176 44.52 E446721021.40.877 88.51 E22855931.70.9221 124.52 E12352871.61.196 16< 152859901.30.757 242343831.20.683 482851891.00.655 72< 152452781.40.956 Unfortunately Relapsed post treatment

7. TWH LIVER CENTRE Mr. Number 1 Now May 2011 Cryos rebound from negative on treatment to 7% Skin lesions return Urinalysis now +ve for protein and blood Develops small ascites No varices What to do now ?

8. TWH LIVER CENTRE Mr. Number 1 May 2011 Treatment # 3 – SAP Boceprevir PegIFNα2b 150mcg/wk + RBV 1200mg/day Plan to add Boceprevir after 4 wks lead-in

9. TWH LIVER CENTRE Treatment # 3 WkHCV RNAALTASTHgbReticLkcANCPlts 07.01 E4901181326.04.5372 236741101633.32.3456 4Detected, < 152356921812.01.2228

10. TWH LIVER CENTRE Treatment # 3 WkHCV RNAALTASTHgbReticLkcANCPlts 07.01 E4901181326.04.5372 236741101633.32.3456 4Detected, < 152356921812.01.2228 8Not detected2345641112.51.7105 10521.50.8105  Erythropoietin 40,000 IU/wk  Blood transfusion q4w  No RBV dose reduction

11. TWH LIVER CENTRE Treatment # 3 WkHCV RNAALTASTHgbReticLkcANCPlts 07.01 E4901181326.04.5372 236741101633.32.3456 4Detected, < 152356921812.01.2228 8Not detected2345641112.51.7105 10521.50.8105 14335181161.30.970 24Not detected2941741.10.817  Erythropoietin 40,000 IU/wk  Blood transfusion q week  Platelets transfusion  Treatment stopped at 24 wks SVR

12. TWH LIVER CENTRE How should his anemia be best managed now ?

13. TWH LIVER CENTRE Anemia Study: EPO vs Ribavirin Dose-Reduction 687 pts received boceprevir/ pegIFN/RBV 500 randomized at time of onset of anemia (Hgb < 10 g/dL) to RBV dose reduction (200-400mg) or Erythropoietin (40,000 IU/wk) Response, %RBV Dose Reduction (n = 249) Erythropoietin (n = 251) End of treatment82 SVR71 Relapse10 Poordad et al. EASL 2012 Abstract 1419.

14. TWH LIVER CENTRE Timing of RBV Dose Reduction Does Not Impact SVR SVR % Poordad F, et al. AASLD 2012. Abstract 154.

15. TWH LIVER CENTRE Degree of RBV Dose Reduction Does Not Impact SVR SVR % Poordad F, et al. AASLD 2012. Abstract 154. Number of RBV dose reduction steps* * step= 200 mg RBV/day decrease for > 3 days

16. TWH LIVER CENTRE Lower SVR Rate if < 50% RBV Received SVR % Poordad F, et al. AASLD 2012. Abstract 154. % of total RBV dose received

17. TWH LIVER CENTRE SVR Rates with RBV Dose Reduction or Erythropoietin in Cirrhotics SVR % Lawitz E et al. AASLD 2012. Abstract 50. n = 438n = 48 ** Cirrhotics more likely to receive secondary intervention than non cirrhotics P=0.59

18. TWH LIVER CENTRE Telaprevir Clinical Trials Pooled Data: RBV Dose Reduction Does Not Impact SVR SVR % Sulkowski et al. EASL 2011. Abstract.

19. TWH LIVER CENTRE Take Home Messages Close monitoring for anemia Close monitoring for anemia RBV dose reduction is the first strategy for managing anemia RBV dose reduction is the first strategy for managing anemia Can reduce dose aggressively i.e. to 600 mg Can reduce dose aggressively i.e. to 600 mg Maintain > 50 % of total RBV dose Maintain > 50 % of total RBV dose Can dose reduce cirrhotics Can dose reduce cirrhotics Cirrhotics may need secondary intervention Cirrhotics may need secondary intervention

20. TWH LIVER CENTRE

21. TWH LIVER CENTRE Higher SVR Rates if RBV Dose Reduced when HCV RNA was Undetectable SVR % Poordad F, et al. AASLD 2012. Abstract 154. HCV RNA