The changing world of hepatitis C

Recently, with the approval of a novel polymerase inhibitor, sofosbuvir (Sovaldi), and a second-generation protease inhibitor, simeprevir (Olysio), treatment of hepatitis C (HCV) has progressed dramatically. These new options offer better cure rates and are more tolerable; however, the costs associated with these new medications are substantial, amounting to several thousands of dollars over the course of treatment. Obviously, the advantages and disadvantages connected with these new therapy options require clinicians, payors, and patients to balance the cost against convenience and effectiveness.

Hepatitis C is a viral disease that leads to inflammation of the liver. It is one of the leading causes of liver transplantation in the United States, where currently, 3.2 million people are infected with the virus. In comparison, 1.2 million people in the United States are living with HIV/AIDS.

As with HIV treatment in the early 1990s, HCV therapy is rapidly evolving from a complex regimen with many drug interactions, side effects, and limited efficacy to a more straightforward regimen and the promise of better patient outcomes.

Most patients with HCV were born between 1945 and 1965. Unfortunately, patients with HCV are commonly asymptomatic. Symptoms of acute infection include jaundice, dark urine, white stools, nausea, and upper-right quadrant pain; long-term complications include cirrhosis and end-stage liver disease. The virus is passed from person to person through the blood, most commonly through shared needles or syringes, needle sticks, and mother-to-child transmission.  While less common, there have been reports of HCV being spread when razors or toothbrushes are shared, as well as through sexual intercourse with a person infected with HCV.

The community pharmacist who becomes familiar with the new screening and treatment guidelines for HCV is poised to play a vital role in the management of this disease.   

Screening

Two-thirds of patients with HCV are asymptomatic; therefore it is imperative to identify patients so that they can be treated appropriately and long-term complications can be prevented.

Among the organizations offering recommendations for screening guidelines are the Centers for Disease Control and Prevention (CDC), the American Association for the Study of Liver Diseases (AASLD), the U.S. Preventative Services Task Force (USPSTF), and the National Institute of Health (NIH).  Table 1 indicates specific recommendations made by individual organizations.^1-4

Once patients are identified for screening, the next step is to obtain an HCV antibody test. Similar to the screening tests for HIV, tests can involve an immunoassay obtained from a blood draw; there is also a rapid test made with an oral swab. After testing proves positive for antibodies, further testing should be conducted to confirm the results.

For most patients, as long as exposure to risk factors does not continue, one screening is appropriate. For those who continue to experience exposure, further screening should be conducted. However, there are no current recommendations as to how often this should be done.

Pharmacotherapy

The pharmacotherapy for HCV is complex, despite the fact that there are only six medications, divided into four pharmacological classes (Table 2).^5-11

Recent updates from the AASLD and Infectious Disease Society of America (IDSA) have provided evidence-based recommendations for pharmacotherapy. Table 3 provides an overview of these recommendations, with the strength of evidence.¹² In short, patients with HCV will require combination therapy; the medications, doses, and duration will be dependent on specific factors, such as genotype, previous treatment history, response rate, and tolerance of therapy based on side effects.

The pharmacotherapy for patients with HCV warrants specific language. Table 4 lists the main clinical terms and their definitions used for the treatment of HCV.¹ This terminology was used extensively before the publication of the new guidelines and medications; however, an understanding of these terms and concepts is still important to mastery of the pharmacotherapy.

Before any initial treatment can occur, patients with HCV must undergo genotype testing. The determination of the HCV genotype is critical for the pharmacotherapy; regimens, doses, duration, and response all vary among the different genotypes.

In HCV, six genotypes exist, but more than 50 subtypes have also been categorized. Genotype 1 is the most common isolate, accounting for 74% of cases in the United States.¹³ While genotypes 2 (15%) and 3 (10%) may not be so common, they are more responsive to current treatment.¹³

^SVR

Historically, the treatment of HCV was based on a combination of ribavirin and peginterferon. The dose and duration were dependent on the factors already listed.

The goal of pharmacotherapy is to eradicate HCV RNA, predicted by the attainment of a sustained virologic response (SVR). Combination therapy of ribavirin and peginterferon has a SVR of only 40% to 50%. When telaprevir (Incivek) and boceprevir (Victrelis) came to market in 2011, the protease inhibitors improved SVR (23% to 88% depending on patient characteristics), but caused severe side effects and drug interactions. 

With the recent addition of sofosbuvir to the market, SVR is increased to 89% to 99%.¹⁴ This dramatic increase in SVR, coupled with the decrease in side effects and potential for treatment as oral therapy only, makes the newer agents groundbreaking. Ultimately, the cost of the newer agents may be high, but the outcomes are incomparable, as shown by the decreased morbidity and mortality.

Pharmacist intervention

Among the changes ushered in with passage of the Affordable Care Act, more patients will have medication coverage to offset the cost of the specialty medications.

As in the case of HIV/AIDS, it is imperative that patients take their medications as prescribed. Pharmacists are at the forefront of patient care, and the profession can play a key role in stressing the importance of adherence at the initial fill and refills.

Compliance packaging is a service that might help patients maintain adherence to their medications, However, the cost of the medication needs to be considered on a store-by-store basis before bottles are opened.

Medication therapy management (MTM)-style meetings can also help increase adherence, by ensuring that patients understand indications for treatment and the side effects they can expect from the therapy.

In light of the high cost of the medications, pharmacies may also provide high-touch services, such as insurance benefits investigation, in order to secure payment from an insurance company.

In short, the pharmacist’s intervention can provide better care for patients, from helping them to understand medication access issues to the necessity of adherence.

Not only can patients benefit from increased care; the pharmacy can benefit as well. The treatment of patients with HCV allows the pharmacy to enter the specialty market. As with other specialty medications, the newer anti-HCV therapies are expensive; while the medications add to total inventory, they might provide better reimbursements.  Also, with better understanding of the world of hepatitis C, a pharmacist can provide such services as patient education on lifestyle changes, future in-house screenings, and the dispensing of evidence-based therapy.

Conclusion

When it comes to managing patients with hepatitis C, the role of the pharmacist is dramatically changing. As specialists who are experts in medications, including drug interactions and administration, and ease of accessibility, pharmacists are poised to make a positive impact on the lives of patients.

To enter the “changing world of hepatitis C,” the first thing pharmacists need is knowledge. They can then augment patient care through their understanding of injection technique, management of the specialty services required to navigate insurance benefits, and provision of accessible help to patients struggling to understand hepatitis C. 

References

1. Ghany MG, Strader DB, Thomas DL, Seeff LB. AASLD Practice Guidelines. Diagnosis, management and treatment of hepatitis C: An Update. 2009. Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hep. 22759.

2. Hepatitis C Information for Health Professionals. CDC website: http:// www.cdc.gov/hepatitis /HCV/GuidelinesC.htm Accessed March 9, 2014.

3. U.S. Preventive Services Task Force. Screening for hepatitis C virus infection in adults: Final recommendation statement. AHRQ Publication No. 12-05174-EF-2. http://www.uspreventiveservicestaskforce.org/uspstf12/hepc/hepcfinalrs.htm.Accessed March 9, 2014.

4. Hepatitis. What You Need to Know. National Digestive Diseases Information Clearinghouse (NDDIC). A service of the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK). National Institutes of Health. http://www.digestive.niddk.nih.gov/ddiseases/pub/hepatitis_ES/index.aspx#2.Accessed March 9, 2014.

5. Sovaldi [package insert]. Forest City, CA: Gilead Sciences, Inc.; 2013. www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/Sovaldi/sovaldi_pi.pdf. Accessed March 9, 2014.

6. Pegasys [package insert]. South San Francisco, CA: Genetech, Inc.; 2013. www.gene.com/download/pdf/pegasys_prescribing.pdf. Accessed March 9, 2013.

7. PegIntron [pacakage insert]. Whitehouse Station, NJ: Merck & Co., Inc.; 2013. www.merck.com/product/usa/pi_circulars/p/peginterferon/pegintron_pi.pdf. Accessed March 9, 2014.

8. Copegus [package insert]. South San Francisco, CA: Genetech, Inc.; 2013. www.gene.com/download/pdf/copegus_prescribing.pdf. Accessed March 9, 2014.

9. Olysio [package insert]. Titusville, NJ: Janssen Therapeutics, Division of Janssen Products; 2013. www.olysio.com/shared/product/olysio/prescribing_information.pdf. Accessed March 9, 2014.

10. Incivek [package insert]. Cambridge, MA: Vertex Pharmaceuticals Inc.; 2013. pi.vrtx.com/files/uspi_telaprevir.pdf. Accessed March 9, 2014.

11. Victrelis [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; 2013. www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf. Accessed March 9, 2014.

12. Recommendations for Testing, Managing, and Treating Hepatitis C. Joint panel from the American Association of the Study of Liver Diseases and the Infectious Diseases Society of America. January 2014. http://www.hcvguidelines.org/.

13. Tice JA. Simeprevir and Sofosbuvir for the Treatment of Chronic Hepatitis C Infections. CTAF [California Technology Assessment Forum]: New Treatments for Patients with Hepatitis C. San Francisco; March 10, 2014. Webcast: http://www.bizvision.com/webcast/prod/54858.

14. Chopra S and Muir AJ. Treatment regimens for chronic hepatitis C virus genotype 1. In: Basow DS, ed. UpToDate. Waltham, MA: UpToDate. www.uptodate.com. Accessed March 12, 2014.

Ben Culpepper is a PGY-2 community pharmacy/academia resident and clinical instructor at UNC Eshelman School of Pharmacy/Kerr Drug, Chapel Hill, NC. John A. (Jake) Galdo is a clinical pharmacy educator at Barney’s Pharmacy, Augusta, Ga.; clinical assistant professor, University of Georgia College of Pharmacy; and clinical instructor, Georgia Regents University College of Dental Medicine.