No 193 March 2016

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Factsheet: Treatments for hepatitis C - Direct Acting Antivirals (DAAs)

This factsheet is abridged and adapted from the original published by Hepatitis NSW on 9 February 2016. It is reprinted with permission.

For more information about anything in this factsheet, if you are in NSW, phone the NSW Hepatitis Infoline on 1800 803 990 or go to www.hep.org.au

If you are in other states, phone the National Hepatitis Information Line on 1800 437 222.

The information in this factsheet will be amended as new information emerges. In particular, the administrative details concerning prescription arrangements for GPs and other doctors still need to be established. New treatment consensus guidelines also are being developed. The purpose of this factsheet is to provide as much information about the new treatments as is currently known.

INTRODUCTION

This year, 2016, is a particularly exciting time for the treatment opportunities for all people in Australia living with hepatitis C. It has been announced that new direct acting antiviral treatment drugs will be listed on the Pharmaceutical Benefits Scheme (PBS) on 1 March 2016.

This factsheet relates to these hepatitis C treatment combinations:

  • Harvoni® (sofosbuvir/ledipasvir) two drugs combined in one pill, taken daily
  • Sovaldi® and Daklinza® (sofosbuvir and daclatasvir) separate pills, taken daily
  • Sovaldi® and Ibavyr® (sofosbuvir and ribavirin) separate pills, taken daily

Other new drugs for treating hepatitis C are currently in different stages of development and/or approval. Over time, these new drugs will also likely be PBS listed and funded, and this factsheet will be amended accordingly.

SUCCESS RATES OF THE NEW TREATMENTS

  • sofosbuvir/ledipasvir = around 95% of people (with genotype 1) achieved cure in Phase 3 studies (see “Defining cure”, below, for an explanation of “cure”).
  • sofosbuvir and daclatasvir = around 95% of people (with genotypes 1 or 3 and no cirrhosis) achieved cure in Phase 3 studies. People with genotype 3 and cirrhosis have lower (although still relatively high) cure rates and will require longer duration or addition of ribavirin.
  • sofosbuvir and ribavirin = around 93% of people (with genotype 2) achieved cure in Phase 3 studies.

The above cure rates relate to people’s hepatitis C genotype and treatment history. They are from Phase 3 clinical trials (researching efficacy in large study groups) and therefore may not apply to reallife populations). Treating doctors will advise which treatment options are suitable for individual people.

TREATMENTS AND GENOTYPES

  • Hep C genotype 1 = sofosbuvir/ledipasvir
    sofosbuvir and daclatasvir
  • Hep C genotype 2 = sofosbuvir and ribavirin
  • Hep C genotype 3 = sofosbuvir and daclatasvir

People with genotypes 4 or 6 remain limited to sofosbuvir taken with pegylated interferon and ribavirin treatment (greater than 90% cure rate).

Other drug combinations are approved and available but those mentioned above are the ones with best response and tolerability.

TREATMENT DURATIONS

sofosbuvir/ledipasvir:

  • = 8 weeks for people with no prior treatment, no cirrhosis and viral load less than 6 million IU/mL
  • = 12 weeks for people with no prior treatment, no cirrhosis and viral load more than 6 million IU/mL
  • = 12 weeks for people with no prior treatment and cirrhosis
  • = 24 weeks for people with prior treatment and cirrhosis

sofosbuvir and daclatasvir:

  • = 12 weeks (although likely longer for people with cirrhosis)
  • = 24 weeks for people with genotype 3 and cirrhosis

sofosbuvir and ribavirin:

  • = 12 weeks for people with genotype 2

sofosbuvir and daclatasvir and ribavirin:

  • = 12 to 16 weeks for people with genotype 3 and cirrhosis.

ARE NEW TREATMENTS TAKEN WITH RIBAVIRIN OR INTERFERON INJECTIONS?

As listed above, sofosbuvir is sometimes taken with ribavirin. Also, sofosbuvir and daclatasvir may additionally be taken with ribavirin for those people who have genotype 3 and cirrhosis.

Importantly, all the new treatments are taken as tablets (pills) and none involve interferon injections.

(Treatment for people with genotypes 4 or 6 involves sofosbuvir taken with pegylated interferon injections and ribavirin tablets.)

TREATMENT SIDE EFFECTS

  • Sofosbuvir/ledipasvir is well tolerated with only minor side effects.
  • Sofosbuvir and daclatasvir are well tolerated with only minor side effects.
  • Sofosbuvir and ribavirin are well tolerated (the most common adverse events of ribavirin are anaemia, fatigue, headache, skin irritation and insomnia).

TREATMENT CONTRAINDICATIONS

There are some drug-drug interaction issues, including amiodarone (an antiarrhythmic medication used to treat ventricular tachycardia or ventricular fibrillation), but most issues will be able to be handled with change of accompanying medications, or through careful monitoring.

Pregnancy must be strictly avoided by both men and women treated with ribavirin in any of the treatment combinations (during treatment and for 24 weeks after). Pregnancy must also be avoided with daclatasvir (during treatment and for 5 weeks after). People should be advised to talk to their doctor or specialist about treatment with sofosbuvir/ledipasvir in pregnancy.

Treating doctors or specialists will advise which treatments would be suitable (or not suitable) for patients, depending on their past and present medical conditions and any other medications they are taking.

PREPARING FOR TREATMENT

People with hepatitis C will have an initial GP or specialist assessment. This will involve full blood testing and likely assessment of their fibrosis stage, via Fibroscan®. People with cirrhosis will be referred for specialist care and treatment. People with cirrhosis require long term monitoring for complications including liver cancer.

(Treatment protocols are currently in development and once they are confirmed, the information in this factsheet will be amended.)

TREATMENT MONITORING AND FOLLOW UP

Treating doctors will probably use a week 4 PCR viral load test to assess treatment adherence as opposed to speed of viral load decline. By week 4, nearly all people are likely to be <1,000 viral load and generally <100 viral load, if they are taking the medication as prescribed.

Some hospital clinics may use different protocols based on whether or not people have other illnesses and the complexity of their hepatitis C disease.

People with no complicating factors may need to have only one on-treatment visit (generally at week 4). This would typically involve blood testing at week 4 for Full Blood Count, Urea & Electrolytes Test, Liver Function and PCR viral load (mentioned above). Some people will require more intensive monitoring/follow-up.

All people will require a PCR viral load test 12 weeks after treatment finishes to check if they are cured.

(Treatment protocols are currently in development and once they are confirmed, the information in this factsheet will be amended.)

DEFINING CURE

“Cure” or “SVR” (Sustained Virological Response) means that someone has cleared hepatitis C virus from their body. If someone has a PCR viral load test which shows undetectable (no virus) at 12 weeks after treatment finished they are considered to be cured.

If hepatitis C has caused significant liver damage, clearing the virus (cure) might not mean that someone is healthy again all of a sudden. In particular, if someone has cirrhosis, they still need specialist care and monitoring. People with cirrhosis still have a potential risk of developing liver cancer, even after being cured of hepatitis C.

People should talk to their treating doctor about what “cure” should mean for them.

This factsheet was developed by Hepatitis NSW. It was reviewed by the Hepatitis NSW Medical and Research Advisory Panel with special input from Prof Gregory Dore and A/Prof Simone Strasser.

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Date last reviewed: 17 March 2016