HEPATITIS C TREATMENT GUIDANCE

HEPATITIS C TREATMENT GUIDANCE

These guidelines have been produced based on the NICE Guidance TA200 Peginterferon alfa and ribavirin for the treatment of chronic hepatitis c and the summaries of product characteristics for PEG IFN 2a (Pegasys Roche) and PEG IFN 2b (Viraferon Peg MSD). This guidance includes the treatment pathways for treatment naïve patients (standard and shortened courses of treatment) and those patients who require re-treatment. Definitions found within this guidance: LVL low viral load This is 800,000 iu / ml at baseline when using PEG IFN 2a (Pegasys) or 600,000 iu / ml at baseline when using PEG IFN 2b (Viraferon peg). HVL high viral load This is 800,000 iu / ml at baseline when using PEG IFN 2a (Pegasys) or 600,000 iu / ml at baseline when using PEG IFN 2b (Viraferon peg) RVR rapid viral response Undetectable levels of hepatitis c RNA 4 weeks after starting treatment. EVR early viral response A 2-log or greater reduction in the levels of hepatitis C RNA 12 weeks after starting treatment. EVRs can be classed as complete (negative hepatitis c RNA levels at week 12 cevr) or incomplete (positive hepatitis c RNA at week 12 but with at least a 2 log reduction from baseline levels ievr) Primary non-responder A patient who fails to achieve and end of treatment response, or in whom treatment is stopped early because early blood tests show failure of viral suppression below predetermined values values that predict failure of response ETR End of treatment response Undetectable levels of hepatitis C RNA on blood testing at the end of planned treatment. Responder relapser A patient who achieved an end of treatment response but has recurrence of detectable virus 6 months after cessation of treatment. SVR sustained viral response Undetectable levels of hepatitis C RNA on blood testing 6 months after completion of antiviral therapy.

Referral Pathway Patient is Hepatitis C antibody positive with a detectable HCV RNA Referral made to Consultant Gastroenterologists East Cheshire NHS Trust Considerations when referring: Current drug use Alcohol use Is the patient homeless? Co-morbidities Referral assessed. Appointment arranged with CNS within 6 weeks of episode being opened. Patient contacted and advised of preinvestigation to avoid Un-necessary appointments Investigations arranged, abdominal ultrasound requested for the same afternoon as hepatitis clinic appointment If no blood tests performed within two weeks contact patient First Clinic Appointment Discuss expectations / patient s wishes Assess for treatment Review investigations Fibroscan Discuss treatment DNA POLICY: At assessment stage: Contact patient after first DNA Discharge after x2 DNAs. Retain details on a database. OUTCOMES Uncomplicated disease Commence treatment within 10 weeks of episode being opened (max. 18weeks). Watch and Wait For patients who do not want treatment. Review 6-12 monthly Consultant Review prior to commencing treatment Investigations are abnormal Significant fibrosis / cirrhosis identified on fibroscan Childs Pugh >B History of decompensation Oesophageal varices Significant co-morbidities Significant psychiatric history

Prescribing Guidance Interferon Two preparations of pegylated interferon are prescribed within East Cheshire NHS Trust. Pegylated Interferon 2a (Pegasys Roche) and Pegylated Interferon 2b (Viraferon Peg MSD). PEG IFN 2a is licensed at a single dose of 180ug / 0.5ml /sc. once weekly PEG IFN 2b is licensed at 1.5ug/kg sc. (upto a maximum dose of 150ug per week) once weekly It may be appropriate to consider the use of non-weight based PEG IFN in those patients who weigh more than 85kg. Ribavirin Two preparations of non-generic ribavirin are currently licensed for the treatment of hepatitis c (Copegus and Rebetol). The licensed dosages of the two ribavirin preparations differ, although there is no evidence of differences in the pharmokinetics of these products. Dosing Recommendations for combination therapy using PEG IFN 2a for hepatitis c positive patients. Genotype Pegasys Dose Ribavirin Dose Duration (standard course) Genotypes 1 /4 180 micrograms < 75kg = 1000mg 48 weeks > 75kg = 1200mg Genotypes 2/3 180 micrograms 800mgs 24 weeks Dosing Recommendations for combination therapy using PEG IFN 2b for hepatitis c positive patients. Body weight (kg) ViraferonPeg (µg/0.5ml) Ribavirin Dose (mg/day) Duration (standard course) <40 50 800 40-50 80 800 51-64 80 800 65-75 100 1000 76-80 120 1000 81-85 120 1200 86-105 150 1200 >105 150 1400 Genotype 1 / 4-48 weeks Genotypes 2 / 3 24 weeks

Treatment Pathways for treatment naïve patients Standard Pathway Pegasys + Copegus (Roche) Genotype 1 / 4 If baseline HCV RNA 800,000 iu / ml consider switching to the shortened pathway Week 12 Has there been a 2 log drop in HCV RNA from baseline? Discontinue treatment Week 24 - Is HCV RNA Continue treatment for 48 weeks Consider withdrawing from treatment as unlikely to achieve SVR Genotype 2 / 3 Continue treatment for 24 weeks If baseline HCV RNA 800,000 iu / ml consider switching to the shortened th

Treatment Pathways for treatment naïve patients Standard Pathway Viraferon Peg + Rebetol Genotype 1 / 4 Week 12 Has there been a 2 log drop in HCV RNA from baseline? If baseline HCV RNA 600,000 iu / ml consider switching to the shortened pathway Discontinue treatment Week 24 - Is HCV RNA Continue treatment for 48 weeks Consider withdrawing from treatment as unlikely to achieve SVR Genotype 2 / 3 license for shortened treatment in patients with Genotypes 2 / 3 Continue treatment for 24 weeks

Treatment Pathways for treatment naïve patients Shortened Pathway Pegasys + Copegus (Roche) Genotype 1 Baseline HCV RNA 800,000 iu / ml Genotype 4 can follow this pathway with no requirement for a low viral load Switch to the standard pathway Week 24 Is HCV RNA still un Consider completing treatment at week 24 Switch to the standard pathway Genotype 2 / 3 Switch to the standard pathway Week 16 Is HCV RNA still un Consider completing treatment at week 16 Switch to the standard pathway When considering a shortened course patients should be free of poor prognostic factors (significant fibrosis / cirrhosis, old age, co-infection, heavy weight). The patient should also be informed of the slightly increased risk of relapse.

Treatment Pathways for treatment naïve patients Shortened Pathway Viraferon Peg + Rebetol Genotype 1 / 4 Baseline HCV RNA 600,000 iu / ml Switch to the standard pathway Week 24 Is HCV RNA still un Consider completing treatment at week 24 Switch to the standard pathway Genotype 2 / 3 license exists When considering a shortened course patients should be free of poor prognostic factors ( significant fibrosis / cirrhosis, old age, co-infection, heavy weight). The patient should also be informed of the slightly increased risk of relapse.

Treatment pathway for patients requiring retreatment Factors to consider: Age Response to primary course Presence of significant fibrosis / cirrhosis ALT Side effects experienced during the primary course Evidence of compliance during primary course Pegasys + Copegus (Roche) Genotype 1 Genotypes 2 / 3 cevr achieved at week 12 If ievr achieved then stop treatment Treat for 72 weeks Treat for 48 weeks Viraferon Peg + Rebetol (MSD) All genotypes Week 12 is HCV RNA Discontinue treatment Continue treatment for 48 weeks