NATIONAL INSTITUTE FOR CLINICAL EXCELLENCE

Health Technology Appraisal

Pegylated interferon alpha 2a and alpha 2b for hepatitis C

Scope

Objective: To establish the clinical and cost effectiveness of pegylated interferon alpha 2a and alpha 2b for the treatment of chronic hepatitis C virus (HCV), relative to current standard treatments, and to produce guidance to the NHS in England and Wales¹

Background: Hepatitis C, a viral disease of the liver, is an important cause of morbidity and mortality in the United Kingdom and many other parts of the world. It frequently causes few or no symptoms at first infection, but has a high probability of becoming an insidious chronic disease. Only about 15% of those infected manage to clear the virus. Around 30% of those with chronic infection will develop cirrhosis of the liver over the next 20-30 years, and a small proportion will go on to develop cancer of the liver. Hepatitis C is one of the main reasons for liver transplantation.

The prevalence in the United Kingdom is uncertain, but estimated to be between 0.1% and 1%. The largest group known to be infected are current and former injecting drug users. Infected blood was the source of infection via clotting factors used in haemophilia and blood transfusions, until these were rendered safe in 1985 and 1991 respectively. Other less common routes of transmission are community-acquired and occupational.

In August 2002, the Department of Health published Hepatitis C Strategy for England in draft form, subject to consultation prior to finalisation. It sets out to improve the effectiveness of prevention, diagnosis and treatment services for hepatitis C.

Technoloy: There has been increasing interest in the use of 'pegylated' interferon. 'Pegylation' is a method for altering the pharmacokinetic characteristics of the drug from the injection site, thus prolonging action, necessitating fewer doses and resulting in greater efficacy. Pegylated interferon can therefore be given (by subcutaneous injection) once a week rather than three times a week as for conventional interferon.

Existing guidance: The existing guidance from the Institute (published in October 2000) recommends that:

Interferon alpha and ribavirin as combination therapy is recommended for the treatment of moderate to severe hepatitis C (defined as histological evidence of significant scarring (fibrosis) and/or significant necrotic inflammation), at standard doses for patient over the age of 18 years as follows:

i) all treatment-naive patients (that is, those who have not previously had interferon alpha monotherapy or combination therapy) and all patients who have been treated with interferon alpha monotherapy, and have had some response but have since relapsed. Such treatments should be continued for 6 months for all patients.

ii) a further 6 months combination therapy is recommended only for patients infected with hepatitis C virus of genotype 1, who respond to therapy by becoming clear of circulating viral RNA as detected by polymerase chain reaction (PCR) in the first 6 months

iii) those in whom liver biopsy poses a substantially increase risk (such as patients with haemophilia) may be treated on clinical grounds without histology.

Therapy involving either or both of these drugs is not in general recommended for patients who are continuing intravenous drug users. Only where the prescribing clinician can be reliably assured that re-infection, compliance and drug interactions pose no problem should patients in this group be considered for combination therapy. Former intravenous drug users including those on oral maintenance therapy need not be excluded from therapy.

Therapy involving either or both of these drugs is not in general recommended for patients who are heavy users of alcohol, because of an increased risk of exacerbation of liver damage.

There is insufficient evidence for making recommendations on combination therapy for patients less than 18 years of age.

There is also insufficient evidence for making recommendations for using combination therapy after liver transplantation.

Interferon alpha monotherapy should be considered only when ribavirin is contraindicated or not tolerated. The recently licensed pegylated interferon monotherapy has not been considered in this guidance.

These recommendations are consistent with the European Association of the Study of the Liver (EASL) guidelines with the exception that (see para. i), those who relapse after initially successful treatment by monotherapy are recommended for 6 months of combination therapy without the necessity of a viral load test after three months.

[Note that EASL guidelines have recently been largely superseded by NIH guidelines (2002).]

¹ The remit from the Department of Health/Welsh Assembly Government is "To appraise the clinical and cost effectiveness of pegylated interferon alphas in their licensed indications and by genotype groups, compared with the current treatment of choice, in the treatment and management of chronic hepatitis C. For patients who can tolerate ribavirin the comparison will be between combination therapy (pegylated interferon alpha + ribavirin) versus combination therapy with conventional interferon alpha; for patients for whom ribavirin is inappropriate or who cannot tolerate ribavirin after commencement of therapy, the comparison will be between pegylated and conventional interferon alpha monotherapy."