Specialty Pharmaceuticals: Therapy Class Review: Hepatitis C Treatment Guidelines

Mr. Allinson is chief executive officer and chief clinical officer of Therigy, LLC.

The American Association for the Study of Liver Diseases (AASLD) recently published its updated practice guidelines for the diagnosis, management, and treatment of hepatitis C.¹ The updated 2009 guidelines include new information and some changes from the last published guidelines, which were published in 2003, and are critical to the community pharmacist who has developed or is interested in developing a hepatitis C virus (HCV) practice. It is through a thorough understanding of the disease, its treatment, and the impact on patients and their families that the pharmacist will develop an optimal specialty therapy management program.

It is estimated that 180 million people worldwide are infected with HCV; although, in the United States, approximately 4.1 million individuals are positive for the antibody to hepatitis C. HCV is the principal cause of death from liver disease and is the leading indication for liver transplantation in the United States.²

For the past 15 years, HCV has been a disease that lends itself very well to the development of a specialty practice, and several well-known specialty pharmacies have built substantial businesses solely on the treatment of HCV. It is an ideal “specialty” for pharmacy due to the complex, self-injected medication therapy; the significant side effects experienced by the patient; and the absolute need for adherence and persistence to achieve good clinical outcomes. Quite often, the gastrointestinal practice is busy and eager to collaborate with and provide direct referrals to a pharmacist who is interested in providing therapy management. For all these reasons, a significant opportunity exists for the pharmacist to provide specialty therapy management, in addition to dispensing the drugs.

Although a comprehensive review of the new guidelines is beyond the scope of this article, some areas of the guidelines can give insight to the opportunity for a community pharmacist interested in building an HCV practice.

Viral Kinetics

HCV can be classified into 6 major genotypes (1-6). Genotype 1 is the most common in the United States, followed by genotypes 2 and 3. Genotypes 4 to 6 are the least common but are increasing, due to the increasing cultural diversity in the United States.³ Knowing the patient’s viral genotype is critical to determining the likelihood of response and the expected duration of therapy. In general, genotype 1 virus will require 48 weeks of therapy, whereas genotypes 2 and 3 will require 24 weeks of therapy.

Because no clinical end point to treatment exists, HCV treatment response is measured with a surrogate marker: an undetectable level of HCV RNA in the serum (“HCV RNA negative”). A successful end-of-treatment response (ETR) is defined as HCV RNA negative following 24 or 48 weeks of treatment. A sustained viral response (SVR) is the ultimate goal of therapy and is defined as HCV RNA negative 24 weeks after treatment cessation.

HCV treatment research is focused not only on new drugs and new drug combinations, but also on viral kinetics— that is, the response of the virus to treatment at different intervals of therapy. For genotype 1 patients, an early viral response (EVR) is measured following 12 weeks of treatment. If the patient has had a ≥2-log drop in their HCV RNA, then they have had an EVR, and that is predictive of an ETR and, ultimately, an SVR. Research continues to focus on a rapid viral response (RVR) at week 4. Genotypes 2 and 3 patients who achieve RVR may be able to shorten their course of treatment; genotype 1 patients with a low initial viral load may possibly shorten their course of therapy.

For the pharmacist, knowing the viral kinetics provides additional information with which to counsel and support the patient. Remaining maximally adherent through these therapy milestones will provide the patient the best opportunity for treatment success; if the virus does not respond, treatment should be stopped, avoiding future exposure to this potent treatment.

Adverse Events

The most common adverse events are the flu-like symptoms (fatigue, headache, and fever), which occur in about one half of patients, and psychiatric side effects (depression, irritability), which occur in about one third of patients. These adverse events are usually the most severe immediately after the patient begins therapy. Without counseling or some assistance, these adverse events often lead to adherence problems or a complete stop in therapy.

Therefore, an ideal role for the pharmacist is to complete a patient assessment and provide behavioral and educational counseling before the patient begins self-injection. This can be done very successfully in a 15- to 20-minute counseling session, which will provide the patient with the understanding of the side effects they are going to experience and practical remedies to manage them. At the same time, the pharmacist can reinforce self-injection training, drug storage and disposal, and the importance of adherence.

Because the pharmacist sees the patient monthly, this is an ideal time to provide a reassessment and determine if the patient is adherent, how they are managing their adverse events (if any), how they are storing their medications, and if any change has taken place to their dose or schedule of administration. This can easily be done in 5 minutes for most patients—obviously, where therapy problems are identified, additional time is spent in counseling.

HIV Coinfection

For patients coinfected with HIV, the urgency for treatment is greater than for patients with HCV infection alone.¹ Unfortunately, the likelihood of achieving SVR is lower in HIV/HCV coinfected patients than in those with HCV monoinfection. As a result, controversy exists as to which HIV/HCV patients should be treated, because the greater risk of cirrhosis must be weighed against the lower SVR rates and additional safety concerns.

For the pharmacist monitoring the coinfected patient undergoing treatment for both diseases, it is important to monitor for signs of ribavirin-associated anemia. Anemia is especially common and more severe in coinfected persons taking azidothymidine (AZT). Ribavirin should not be used in patients taking didanosine (ddI), because it potentiates the toxicity of ddI. The AASLD guidelines recommend that, when possible, patients receiving AZT and especially ddI should be switched to an equivalent antiretroviral agent before beginning ribavirin therapy.

Alcohol Use

One of the most common general patient management issues is the use of alcohol by the HCV-infected patient undergoing treatment. During counseling, patients often inquire if they must abstain completely from alcohol while on treatment. Or, they may call the pharmacist to inquire if they can have “a drink or 2” at a special occasion they are attending. A strong relationship exists between the use of excess alcohol and the development or progression of liver fibrosis. Furthermore, excess alcohol may increase HCV RNA replication and interfere with treatment response. In answer to one of the most likely questions a pharmacist will receive from the HCV patient under treatment, the guidelines provide the following suggestion: “although no consensus opinion exists, it seems reasonable to recommend either the complete suspension of alcohol intake while on treatment or restricting its use to an occasional drink during the course of therapy.”¹

Regarding the use of herbals, recommendation 65 in the guidelines states conclusively that “there is no current evidence that herbal products have a role in the treatment of patients with acute or chronic HCV infection.”¹

Summary

In conclusion, the pharmacist has an important role to play in the provision of pharmaceutical care to patients undergoing treatment for HCV. For those who have a practice or want to develop an HCV practice, it is critically important to understand the disease and the new AASLD Practice Guidelines. They contain a wealth of information about HCV and provide an invaluable foundation for the care of these patients. â– 

References

1. Ghany M, Strader D, Thomas D, Seeff LB, American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4);1335-1374.

2. Kim WR. The burden of hepatitis C in the United States. Hepatology. 2002;36(5 suppl 1):S30-S34.

3. Nainan OV, Alter MJ, Kruszon-Moran D, et al. Hepatitis C virus genotypes and viral concentrations in participants of a general population survey in the United States. Gastroenterology. 2006;131(2):478-484.