Clinical UM Guideline


Subject:Hepatitis C Pegylated Interferon Antiviral Therapy
Guideline #:  CG-DRUG-07Current Effective Date:  04/15/2014
Status:RevisedLast Review Date:  02/13/2014

Description

This document addresses the treatment of hepatitis C infection with pegylated interferon therapy, peginterferon alfa-2a or peginterferon alfa-2b as monotherapy, as dual therapy in combination with ribavirin, or as triple therapy utilizing ribavirin and a serine protease inhibitor (for example, boceprevir, simeprevir, or telaprevir) or polymerase inhibitor (for example, sofosbuvir).

Note: Please see the following related document for additional information:

Clinical Indications

Note: For the purposes of this document, the following definitions apply:

Medically Necessary:

  1. Treatment of Hepatitis C Virus (HCV) Genotype 1:
    1. Triple therapy – through week 12 with a polymerase inhibitor:
      Pegylated interferon as part of a planned triple therapy in combination with ribavirin and polymerase inhibitor is considered medically necessary in individuals (18 years or older) with confirmed HCV genotype 1 for a maximum of 12 weeks of therapy when all of the following criteria have been met:
      1. Detectable HCV ribonucleic acid (RNA); AND
      2. Compensated liver disease; AND
      3. Individual has not received previous treatment for HCV with triple therapy.
    2. Initial triple therapy – through week 12 with a serine protease inhibitor:
      Pegylated interferon as part of a planned triple therapy in combination with ribavirin and serine protease inhibitor is considered medically necessary in individuals (18 years or older) with confirmed HCV genotype 1 for up to a total of 12 weeks of initial therapy when all of the following criteria have been met:
      1. Detectable HCV ribonucleic acid (RNA); AND
      2. Compensated liver disease; AND
      3. Individual has not received previous treatment for HCV with triple therapy.
    3. Continuation of triple therapy – through week 48:
      Pegylated interferon as part of triple therapy in combination with ribavirin and serine protease inhibitor is considered medically necessary in individuals (18 years or older) with HCV genotype 1 currently receiving a 12 week course of triple therapy who require up to an additional 36 weeks of treatment (to complete up to a total of 48 weeks) of therapy when one of the following criteria has been met:
      1. Decrease in HCV RNA to less than 1000 IU/mL for telaprevir-based triple therapy at week 12 of initial therapy, or
      2. Decrease in HCV RNA to less than100 IU/mL for boceprevir-based triple therapy at week 12 of initial therapy; or
      3. Decrease in HCV RNA to less than 25 IU/mL for simeprevir based triple therapy at week 12 of initial therapy
    4. Initial dual therapy – through week 12:
      Pegylated interferon as part of dual therapy (with ribavirin) is considered medically necessary in individuals with confirmed HCV genotype 1 for up to a total of 12 weeks of initial therapy when all of the following criteria have been met:
      1. Detectable HCV RNA; AND
      2. Compensated liver disease; AND
      3. When one of the following criteria has been met:
        1. Individual has not received previous treatment with pegylated interferon in combination with ribavirin; or
        2. Individual with significant fibrosis or cirrhosis who has received one of the following treatments without any demonstrated response, or have relapsed:
          1. Non-pegylated interferon monotherapy, or
          2. Non-pegylated interferon with ribavirin, or
          3. Pegylated monotherapy.
    5. Continuation of dual therapy – through week 48:
      Pegylated interferon as part of dual therapy (with ribavirin) is considered medically necessary in individuals with HCV genotype 1 currently receiving a 12 week course of dual therapy who require an additional 36 weeks of treatment (to complete a total of 48 weeks) of therapy when one of the following criteria has been met:
      1. Documented early viral response (EVR). An EVR is defined as a decrease in HCV RNA greater than 2 log from baseline; or
      2. Decrease in HCV RNA to undetectable levels at week 12 of initial therapy.
    6. Slow responders to initial dual therapy:
      Pegylated interferon as part of dual therapy (with ribavirin) is considered medically necessary in individuals with HCV genotype 1 who are slow responders, defined as HCV RNA test becomes negative between weeks 12 and 24 of initial dual therapy, for a maximum treatment duration of 72 weeks.
  2. Treatment of HCV Genotype 2 or 3
    1. Triple therapy – through week 12 with a polymerase inhibitor:
      Pegylated interferon as part of a planned triple therapy in combination with ribavirin and polymerase inhibitor is considered medically necessary in individuals (18 years or older) with confirmed HCV genotype 2 for a maximum of 12 weeks of therapy when all of the following criteria have been met:
      1. Detectable HCV ribonucleic acid (RNA); AND
      2. Compensated liver disease; AND
      3. Demonstrated partial or no response to initial dual therapy with pegylated interferon in combination with ribavirin; AND
      4. Individual has not received previous treatment for HCV with triple therapy.

        Pegylated interferon as part of a planned triple therapy in combination with ribavirin and polymerase inhibitor is considered medically necessary in individuals (18 years or older) with confirmed HCV genotype 3 for a maximum of 12 weeks of therapy when all of the following criteria have been met:
      1. Detectable HCV ribonucleic acid (RNA); AND
      2. Compensated liver disease; AND
      3. Individual has not received previous treatment for HCV with triple therapy.
    2. Dual therapy – through week 24:
      Pegylated interferon as part of dual therapy (with ribavirin) is considered medically necessary in individuals with confirmed HCV genotype 2 or 3, for an initial course of treatment not to exceed 24 weeks in duration for individuals with all the following conditions:
      1. Detectable HCV RNA; AND
      2. Compensated liver disease; AND
      3. Individual has not received previous therapy with pegylated interferon in combination with ribavirin.
    3. Dual therapy – through week 48:
      Pegylated interferon as part of dual therapy (with ribavirin) is considered medically necessary in individuals with confirmed HCV genotype 2 or 3, for a course of treatment not to exceed 48 weeks in duration for individuals who meet both of the following conditions:
      1. Detectable HCV RNA; AND
      2. Individual has HIV coinfection, or demonstrated no response to initial dual therapy (with ribavirin), or has relapsed after treatment with one of the following:
        1. Non-pegylated interferon monotherapy; or
        2. Non-pegylated interferon with ribavirin; or
        3. Pegylated monotherapy.
  3. Treatment of HCV Genotype 4, 5 or 6
    1. Triple therapy – through week 12 with a polymerase inhibitor:
      Pegylated interferon as part of a planned triple therapy in combination with ribavirin and polymerase inhibitor is considered medically necessary in individuals (18 years or older) with confirmed HCV genotype 4 for a maximum of 12 weeks of therapy when all of the following criteria have been met:
      1. Detectable HCV ribonucleic acid (RNA); AND
      2. Compensated liver disease; AND
      3. Individual has not received previous treatment for HCV with triple therapy.

        Pegylated interferon as part of a planned triple therapy in combination with ribavirin and polymerase inhibitor is considered medically necessary in individuals (18 years or older) with confirmed HCV genotype 5 or 6 for a maximum of 12 weeks of therapy when all of the following criteria have been met:
      1. Detectable HCV ribonucleic acid (RNA); AND
      2. Compensated liver disease; AND
      3. Individual has not received previous treatment for HCV with triple therapy; AND
      4. When one of the following criteria have been met:
        1. Individual has not received initial treatment with pegylated interferon in combination with ribavirin; or
        2. Demonstrated relapse after initial dual therapy with pegylated interferon in combination with ribavirin.
    2. Initial dual therapy – through week 12:
      Pegylated interferon as part of dual therapy (with ribavirin) is considered medically necessary in individuals with confirmed HCV genotype 4, 5 or 6 for up to a total of 12 weeks of initial therapy when all of the following criteria have been met:
      1. Detectable HCV RNA; AND
      2. Compensated liver disease; AND
      3. When one of the following criteria has been met:
        1. Individual has not received previous treatment with pegylated interferon in combination with ribavirin; or
        2. Individual with significant fibrosis or cirrhosis who has received one of the following treatments without any demonstrated response, or has relapsed:
          1. Non-pegylated interferon monotherapy, or
          2. Non-pegylated interferon with ribavirin, or
          3. Pegylated monotherapy.
    3. Continuation of dual therapy – through week 48:
      Pegylated interferon as part of dual therapy (with ribavirin) is considered medically necessary in individuals with HCV genotype 4, 5 or 6 currently receiving a 12 week course of combination pegylated interferon and ribavirin therapy who require an additional 36 weeks of treatment (to complete a total of 48 weeks) of therapy when one of the following criteria has been met:
      1. Documented EVR. An EVR is defined as a decrease in HCV RNA greater than 2 log from baseline; or
      2. Decrease in HCV RNA to undetectable levels at week 12 of initial therapy.
  4. HCV antiviral therapy in individuals with a contraindication to Ribavirin:
    Pegylated interferon monotherapy is considered medically necessary in individuals with a contraindication to ribavirin and confirmed HCV with compensated liver disease for up to 48 weeks when all of the following criteria have been met:
    1. Any genotype; AND
    2. Detectable HCV RNA; AND
    3. When one of the following criteria has been met:
      1. Individual has not received previous treatment with pegylated interferon monotherapy; or
      2. Individual has received previous non-pegylated interferon monotherapy with no response or relapse has occurred.

Not Medically Necessary: 

Treatment of HCV with ribavirin as monotherapy is considered not medically necessary for the treatment of hepatitis C.

Treatment of HCV with pegylated interferon as monotherapy, or as part of dual or triple therapy is considered not medically necessary when any of the criteria specified above are not met, or in individuals when any of the following contraindications are present:

  1. Uncontrolled depression (for example, suicide risk); or
  2. Autoimmune hepatitis or other condition known to be exacerbated by interferon and ribavirin; or
  3. Pregnant women or those who may become pregnant; or
  4. Severe concurrent diseases including, but not limited to, severe hypertension, heart failure, significant coronary artery disease, poorly controlled diabetes or obstructive pulmonary disease; or
  5. Untreated hyperthyroidism; or
  6. Children under 3 years of age; or
  7. Known hypersensitivity to drugs used to treat hepatitis C; or
  8. A recipient of kidney, heart, or other solid organ transplant except liver transplant (note: antiviral therapy post liver transplantation should be undertaken with caution and performed under the supervision of a physician experienced in transplantation).

Treatment of HCV genotype 1 with pegylated interferon is considered not medically necessary when the criteria specified above are not met, or for any of the following:

  1. Triple therapy beyond 12 weeks using a polymerase inhibitor; or
  2. Triple therapy beyond 48 weeks using a serine protease inhibitor; or
  3. Dual therapy beyond 48 weeks when there was a response to initial therapy; or
  4. Dual therapy beyond 72 weeks for slow responders.

Treatment of HCV genotype 2, 3, 4, 5 and 6 with pegylated interferon in combination with ribavirin and polymerase inhibitor is considered not medically necessary beyond 12 weeks when the criteria specified above are not met.

Treatment of HCV genotype 2, 3, 4, 5, and 6 with pegylated interferon beyond 48 weeks is considered not medically necessary.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS 
S0145Injection, pegylated interferon alfa-2a, 180 mcg per ml (Pegasys)
S0148Injection, pegylated interferon alfa-2b; 10 mcg (Peg Intron)
S9559Home injectable therapy; interferon, including administrative services, care coordination, and all necessary supplies and equipment, per diem
  
ICD-9 Diagnosis[For dates of service prior to 10/01/2014]
070.41Acute hepatitis C with hepatic coma
070.44Chronic hepatitis C with hepatic coma
070.51Acute hepatitis C without mention of hepatic coma
070.54Chronic hepatitis C without mention of hepatic coma
070.70-070.71Unspecified viral hepatitis C
  
ICD-10 Diagnosis[For dates of service on or after 10/01/2014]
B17.10-B17.11Acute hepatitis C
B18.2Chronic viral hepatitis C
B19.20-B19.21Unspecified viral hepatitis C
  
Discussion/General Information

The hepatitis C virus (HCV) was identified in 1989 and found to account for most infections previously termed "non-A, non-B hepatitis." It is a common and serious disease accounting for approximately 15 percent of reported cases of acute viral hepatitis, 60 to 70 percent of chronic hepatitis, and up to 50 percent of cirrhosis, end-stage liver disease, and liver cancer (hepatocellular carcinoma [HCC]). According to the Centers for Disease Control (CDC) (2010), approximately 1.8 percent of the U.S. population (4.1 million persons exposed and 3.2 million persons chronically infected) revealed antibodies to HCV, indicating ongoing or previous infection with the virus and resulting in an estimated 16,000 deaths annually. A distinct and major characteristic of hepatitis C is its tendency to cause chronic liver disease and liver failure.

Liver failure from chronic hepatitis C is one of the most common indications for liver transplantation in the United States. It is estimated that 70% of all HCV-infected individuals will eventually go on to develop chronic liver disease; at least 20 percent will develop cirrhosis, a process that takes 10 to 20 years. After 20 to 40 years, a smaller percentage of those individuals with chronic disease develop HCC. The population identified as high-risk for developing HCC includes males, people with a history of substance abuse, those diagnosed with cirrhosis, people over age 40, and those infected for 20 to 40 years.

There are six known genotypes of HCV with genotype 1 (75%), genotype 2 (approximately 10%), and genotype 3 (approximately 10%) being most common in the United States. People with genotypes 2 and 3 are almost three times more likely to respond to therapy than those with genotype 1. Genotyping can also be used to determine the duration of treatment for many people. For those with genotype 2 or 3, a 24-week course of combination therapy is usually sufficient. Individuals with genotype 1 who have responded at the end of 12 weeks of treatment may benefit from an additional 36 weeks of treatment. For those individuals with genotype 1 who are identified as slow responders (HCV RNA test becomes negative between weeks 12 and 24), the American Association for the Study of Liver Disease (AASLD) has recommended extending treatment to 72 weeks (AASLD, 2009). For those with genotype 4, the American Gastroenterological Association (AGA) recommends treatment for 48 weeks with combination therapy. The hepatitis C virus replicates inside its host every 7 to 9 hours and typically produces about 1 trillion viral copies per day. According to the National Institute for Health and Clinical Excellence (NICE, 2004), treatment for individuals infected with HCV genotype 5 or 6 should mirror that of HCV genotype 1 and 4 using pegylated therapy and ribavirin. According to the recommendations, individuals should receive an initial 12 weeks of treatment, if there is a decrease in HCV RNA greater than 2 log from baseline treatment , until 48 weeks. The authors also concluded that "people infected with more than one genotype that includes one or more of genotypes 1, 4, 5, or 6 should be treated as genotype 1."

Chronic hepatitis C varies greatly in its course and outcome. At one end of the spectrum are individuals who exhibit no signs or symptoms of liver disease and have completely normal levels of serum liver enzymes. Liver biopsy has been used to determine the stage of fibrosis and the degree of inflammation, which assist in determining prognosis. Biopsy results usually show some degree of chronic hepatitis, but the degree of injury is usually mild, and the overall prognosis may be good. At the other end of the spectrum are individuals with severe hepatitis C who have symptoms, HCV RNA (ribonucleic acid) in serum, elevated serum liver enzymes, and who ultimately develop cirrhosis and end-stage liver disease. In the middle of the spectrum are individuals who have few or no symptoms, mild to moderate elevations in liver enzymes, and an uncertain prognosis. For individuals with HCV genotype-1 infection, clinicians are more likely to proceed with liver biopsy as a guide for treatment. Whereas those with HCV genotype-2 or 3 who are very likely to respond to therapy, the clinician may not resort to liver biopsy (AASLD, 2009).

Currently, combination therapy with oral ribavirin and pegylated interferon alfa 2a or 2b injection (Pegasys®, Hoffman-La Roche Inc., Nutley, NJ or PegIntron®, Schering Corporation, Kenilworth, NJ) is the standard of care for the treatment of chronic hepatitis C. Combination therapy with pegylated interferon products has been more effective than interferon alfa alone in interferon-naïve subjects. Treatment-naïve subjects have a 41%- 56% sustained viral response (SVR) with combination pegylated interferon and ribavirin (Rebetol® Schering Corporation, Kenilworth, NJ, Copegus®, Roche Laboratories Inc., Nutley, NJ or Ribasphere®, Three Rivers Pharmaceuticals, LLC, Warrendale, PA) therapy. Subjects who have relapsed on previous non-pegylated interferon therapy have a 49% SVR, and non-responders to non-pegylated interferon monotherapy have a 25%-40% response (Shepherd, 2004). According to the U.S. Food and Drug Administration (FDA) label for ribavirin, the intended use for treatment of hepatitis C is in combination with pegylated-interferon and not as a monotherapy, when criteria are met.

In May 2011, Incivek (Vertex Pharmaceuticals Inc., Cambridge, MA) and Victrelis (Schering Corp., Whitehouse Station, NJ) were approved by the U.S. FDA for treatment of chronic hepatitis C genotype 1 infection in combination with pegylated interferon and ribavirin, in adults with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy.

The FDA approved labeling for boceprevir (Victrelis) includes additional precautions for use in specific populations (Product Information Label, 2013):

Geriatric Use

Hepatic Impairment

Hepatitis B Virus (HBV) Co-Infection

Human Immunodeficiency Virus (HIV) Co-Infection

Nursing Mothers

Organ Transplantation

Pediatric Use

Pregnancy

Renal Impairment

The FDA approved labeling for telaprevir (Incivek) includes additional precautions for use in specific populations (Product Information Label, 2013):

Co-infection

Geriatric Use

Hepatic Impairment

Pediatrics Use

Pregnancy

Renal Impairment

Solid Organ Transplantation

According to the 2011 AASLD update on treatment of genotype 1 chronic hepatitis C virus infection, the use of pegylated interferon and ribavirin remain key components of therapy in treatment of this disease. The emergence of triple therapy with the addition of the serine protease NS3/4A (boceprevir and telaprevir) inhibitors provides options for the treatment-naïve and treatment-experienced individuals with HCV genotype 1 disease.

In November 2013, simeprevir (Olysio™) (Janssen Therapeutics, Titusville, NJ), an HCV NS3/4A protease inhibitor, received approval by the U.S. FDA for treatment of chronic hepatitis C genotype 1 infection as a component of a combination antiviral treatment regimen. Simeprevir efficacy has been established in combination with peginterferon alfa and ribavirin in HCV genotype 1 infected subjects with compensated liver disease (including cirrhosis). Simeprevir is not indicated for use as a monotherapy. FDA approval was based on results of unpublished randomized, placebo-controlled studies in 1,178 subjects with hepatitis C genotype 1 infections. In the treatment –naïve individuals at 12 weeks of therapy, the simeprevir triple therapy group had a higher SVR than group who received treatment with the dual therapy (80% vs. 50%). In participants who had a relapse on interferon-based therapy, the addition of simeprevir improved SVR response (79% vs. 37%) at 12 weeks. Although these results are encouraging, it is important to note that there is a genotype 1a strain (with NS3 Q80K polymorphism) for which simeprevir will not be efficacious. For this reason, those with genotype 1 infections should be screened, and alternate therapy is recommended for those with Q80K polymorphism.

In December 2013, sofosbuvir (Sovaldi™) (Gilead Sciences, Inc., Foster City, CA), a HCV nucleotide analog NS5B polymerase inhibitor, received approval by the U.S. FDA for treatment of CHC infection as a component of a combination antiviral treatment regimen. Sofosbuvir efficacy has been established in adults with HCV genotype 1 and 4 infection, including those with HCV/HIV-1 co-infection when administered in combination with pegylated interferon and ribavirin. Lawitz and colleagues (2013) reported results from the NEUTRINO study, a phase III open-label, single-arm trial that evaluated 12 weeks of treatment with sofosbuvir combined with peginterferon-ribavirin in treatment naïve subjects with genotype 1, 4, 5 and 6 HCV infection (98% had genotype 1 or 4). The overall SVR rate at 12 weeks for treatment-naïve subjects with genotype 1 and 4 HCV infection was 90% and 96% at 12 weeks, respectively. Adverse events included fatigue, headache, nausea and neutropenia, less common with sofosbuvir than with peginterferon.

According to the AASLD/ Infectious Diseases Society of America (IDSA) 2014 updated practice guideline,  recommendations for testing, managing and treating hepatitis C include off-label recommendations for individuals who are initiating therapy for HCV infection or who experienced relapse after combination peginterferon alfa and ribavirin therapy in genotype 3, 5 and 6 using triple therapy with Sovaldi, peginterferon alfa and ribavirin. In those individuals who previously received peginterferon alfa and ribavirin therapy and who had failed treatment (partial or no response), the guideline included recommendation using triple therapy regimen with Sovaldi, peginterferon alfa and ribavirin in genotype 2 and 3. The recommendations are based on a 2A category of evidence.

The FDA-approved labeling for simeprevir includes additional precautions for use in specific populations (Product Information Label, 2013):

Geriatric Use

Hepatic Impairment

Liver Transplantation

Nursing Mothers

Other HCV Genotypes

Pediatric Use

Pregnancy

Race

Renal Impairment

The FDA-approved labeling for sofosbuvir includes additional precautions for use in specific populations (Product Information Label, 2013): 

CHC with Genotype 5 or 6 HCV Infection

HCV/HIV-1 Co-infection

Hepatic Impairment

Nursing Mothers

Pediatric Use

Pregnancy

Renal Impairment

Post-Liver Transplant

The National Institute of Health (NIH) consensus statement on HCV states pegylated-interferon in combination with ribavirin is an appropriate therapy for non-responders and for those who relapse after previous interferon monotherapy or in combination with ribavirin. The yield of retreatment may be as small as 15 to 20% of non-responders to standard interferon.

At this time, there is a paucity of evidence to support the retreatment of individuals who have relapsed after previous treatment with pegylated interferon/ribavirin combination therapy.

There is limited peer reviewed literature addressing the net health outcomes in individuals with decompensated cirrhosis with evidence of clinical complications and/or profound thrombocytopenia or leukopenia. However, for a subset of individuals with cirrhosis and decompensation (generally MELD [Model for End-stage Liver Disease] score less than 18), low accelerating doses of interferon and ribavirin combination therapy, with or without growth factors, may slow progression or prevent complications. Therefore, such cases should be reviewed on an individual basis.

Results of several uncontrolled studies demonstrate that individuals with acute HCV, as confirmed by HCV RNA, who fail to spontaneously clear the virus within 12 weeks of the onset of symptomatic disease, may also benefit from pegylated interferon therapy, and such cases will be considered on an individual basis. Due to the lack of controlled studies in this population, definitive recommendations regarding the initiation, dosing of pegylated interferon, or duration of therapy have yet to be determined.

Definitions

Child-Pugh Score (also known as Child-Turcotte-Pugh score): A scoring system for severity of liver disease and likelihood of survival based on the presence of: degenerative disease of the brain (encephalopathy), the escape or accumulation of fluid in the abdominal cavity (ascites), laboratory measures of various substances in the blood (see table below), and the presence of other co-existing diseases; after calculating the CTP score using a table similar to the one below, individuals can be classified into one of three categories:

Variable

1 Point

2 Points

3 Points

EncephalopathyNoneModerateSevere
AscitesNoneMildModerate
Albumin (mg/dL)Greater than 3.52.8-3.5Less than 2.8
Prothombin time (International Normalized ratio) prolongedLess than 44-6Greater than 6
Bilirubin (mg/dL)
Primary biliary cirrhosis
Cirrhosis/primary
Primary sclerosing cholangitis
1-44-10Greater than 10
All other diseasesLess than 21-3Greater than 3

Compensated liver disease: Child-Pugh score less than or equal to 6 (class A) in cirrhotic individuals before or during treatment.

Decompensated liver disease: Child-Pugh score greater than 6 (class B or class C) in cirrhotic individuals before or during treatment.

References

Peer Reviewed Publications:

  1. Ahmed F, Jacobson IM. Treatment of relapsers after combination therapy for chronic hepatitis C. Gastroenterol Clin North Am. 2004; 33(3):513-526.
  2. Arenas JI, Vargas HE. Hepatitis C antiviral therapy in patients with cirrhosis. Gastroenterol Clin North Am. 2004; 33(3):549-562.
  3. Berenguer M, Wright T. Treatment strategies for hepatitis C: intervention prior to liver transplant, pre-emptively or after established disease. Clin Liver Dis. 2003; 7(3):631-650.
  4. DeFrancesco R, Rice CM. New therapies on the horizon for hepatitis C. Clin  Liver Dis. 2003; 7(1):211-242.
  5. Dove, L. A general approach to the management of chronic hepatitis C. Gastroenterol Clin North Am. 2004; 33(3):463-477.
  6. Flamm SL. Chronic hepatitis C virus infection. JAMA. 2003; 289(18):2413-2417.
  7. Fontana RJ. Nonresponders to hepatitis C virus therapy: pegylated interferons and beyond. Gastroenterol Clin North Am.2004; 33(3):527-547.
  8. Hadziyannis SJ, Sette H, Morgan TR, et al. Peginterferon-a2a and ribavirin combination therapy in chronic hepatitis C. Ann Internal Med. 2004; 140:346-355.
  9. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013; 368(20):1878-1887.
  10. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet. 2001; 358:958-965.
  11. Oh S, Afdhal NH. Antiviral therapy for treatment naïve patients with hepatitis C virus. Gastroenterol Clin North Am. 2004; 33(3):497-511.
  12. Shepard J, Brodin H, Cave C, et al. Pegylated interferon µ-2a and -2b in combination with ribavirin in the treatment of chronic hepatitis C: a systematic review and economic evaluation. Health Technol Assess. 2004; 8(39).
  13. Ward RP, Kugelmas M, Libsch KD. Management of hepatitis C: evaluating suitability for drug therapy. Am Fam Physician. 2004: 69(6):E1429-1438. Available at: http://www.aafp.org/afp/20040315/1429.html. Accessed on December 31, 2013. 

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American Association for the Study of Liver Disease (AASLD). Ghany MG, Nelson DR, Strader DB, et al. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases. Available at: http://www.aasld.org/practiceguidelines/Documents/2011UpdateGenotype1HCVbyAASLD24641.pdf. Accessed on December 31, 2013.
  2. American Association for the Study of Liver Disease (AASLD). Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management and treatment of hepatitis C: an update. 2009. Available at: http://www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/Diagnosis_of_HEP_C_Update.pdf. Accessed on December 31, 2013.
  3. American Association for the Study of Liver Disease (AASLD). Recommendation for testing, managing, and treating hepatitis C. January 2014. Accessed on: http://www.hcvguidelines.org/sites/default/files/full_report.pdf. Accessed on February 20, 2014.
  4. American Hospital Formulary Services® (AHFS). AHFS Drug Information 2013®. Bethesda, MD: American Society of Health-System Pharmacists®; 2013.
  5. Boceprevir. In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated December 23, 2013. Available at: http://www.micromedexsolutions.com. Accessed on December 31, 2013.
  6. Boyer JL, Chang EB Collyar DE, et al. Management of Hepatitis C: National Institutes of Health Consensus Development Conference Statement. 2002.
  7. Copegus [Product Information], Nutley, NJ. Roche Laboratories, Inc.; February 2013. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021511s026lbl.pdf. Accessed on December 31, 2013.
  8. Dienstag JL, McHutchison JG. American Gastroenterological Association medical position statement on the management of hepatitis C. Gastroenterology 2006; 130(1):225-230. Available at: http://www.gastrojournal.org/article/PIIS0016508505022717. Accessed on December 31, 2013.
  9. Dienstag JL, McHutchison JG. American Gastroenterological Association technical review on the management of hepatitis C. Gastroenterology. 2006; 130 (1):231-264. Available at: http://www.gastrojournal.org/article/PIIS0016508505022705. Accessed on December 31, 2013.
  10. Incivek [product Information], Cambridge, MA. Vertex Pharmaceuticals Inc; October 2013. Available at: http://pi.vrtx.com/files/uspi_telaprevir.pdf. Accessed on December 31. 2013.
  11. National Institute for Health and Clinical Excellence. Technology appraisal guidance 75. Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of chronic hepatitis C. (Review and extension of technology appraisal guidance 14). Updated November 2013. Available at: http://www.nice.org.uk/nicemedia/live/11524/32809/32809.pdf. Accessed on December 31, 2013.
  12. Pegasys [Product Information], Nutley, NJ. Hoffman-La Roche Inc; July 2013. Available at: http://www.gene.com/download/pdf/pegasys_prescribing.pdf. Accessed December 31, 2013.
  13. Peginterferon Alfa-2a. In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated August 26, 2013. Available at: http://www.micromedexsolutions.com. Accessed on December 31, 2013.
  14. Peginterferon Alfa-2b (systemic). In: DrugPoints System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated August 26, 2013. Available at: http://www.micromedexsolutions.com. Accessed on December 31, 2013.
  15. PegIntron [Product Information], Kenilworth, NJ. Schering Corporation; November 2013. Available at: http://www.merck.com/product/usa/pi_circulars/p/pegintron/pegintron_pi.pdf. Accessed on December 31, 2013.
  16. Rebetol [Product Information], Kenilworth, NJ. Schering Corporation. November 2013. Available at: http://www.spfiles.com/pirebetol.pdf. Accessed on December 31, 2013.
  17. Ribasphere [Product Information], Greenville, NC.DSM Pharmaceuticals, Inc; December 2013. Available at: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=41798. Accessed on October 15, 2013.
  18. Ribavirin. In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated December 20, 2013. Available at: http://www.micromedexsolutions.com. Accessed on December 31, 2013.
  19. Simeprevir. In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated January 2, 2014. Available at: http://www.micromedexsolutions.com. Accessed on January 13, 2014.
  20. Simeprevir [Product Information], Titusville, NJ. Janssen Therapeutics. December 2013. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/205123s001lbl.pdf. Accessed on December 31, 2013.
  21. Sofosbuvir. In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated December 20, 2013. Available at: http://www.micromedexsolutions.com. Accessed on January 3, 2014.
  22. Sofosbuvir [Product Information], Foster City, CA. Gilead Sciences. December 2013. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204671s000lbl.pdf. .Accessed on December 31, 2013.
  23. Telaprevir. In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated December 19, 2013. Available at: http://www.micromedexsolutions.com. Accessed on December 31, 2013.
  24. Victrelis [Product Information], Whitehouse Station, NJ. Schering Corporation; September 2013. Available at: http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf. Accessed on December 31, 2013.
Index

Boceprevir
Copegus
Hepatitis C
Peginterferon alfa 2-a [Pegasys]
Peginterferon alfa-2b [PegIntron]
Pegylated Interferon Therapy
Rebetol
Ribasphere
Ribavirin
Simeprevir
Sofosbuvir
Telaprevir

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Revised02/13/2014Medical Policy & Technology Assessment Committee (MPTAC) review. Added medically necessary statement for HCV genotype 1, 2, 3, 4, 5 and 6 triple therapy using polymerase inhibitor. Revised medically necessary statement for initial triple therapy and continuation of triple therapy using serine protease inhibitor. Revised not medically necessary statement to address polymerase inhibitor and serine protease inhibitor. Updated Description, References, Websites and Index.
Revised11/14/2013MPTAC review. Clarified medically necessary criteria for initial treatment and re-treatment of HCV genotype 1 with pegylated interferon as part of triple therapy. Updated Discussion, References and Websites.
Reviewed11/08/2012MPTAC review. Updated Discussion, References and Websites.
Revised11/17/2011MPTAC review. Medically necessary statements updated to address initial treatment and re-treatment of HCV genotype 1 with pegylated interferon as part of triple therapy. Clarified medically necessary criteria for genotype 2 and 3. Updated not medically necessary statements. Description, Background, Index, References and Websites updated.
Revised08/18/2011MPTAC review. Medically necessary statement updated to address coverage for genotypes 5 and 6. Clarified not medically necessary contraindications and statements. Updated Definitions, Websites and References.
Reviewed08/19/2010

MPTAC review.

Websites and References updated. Updated Coding section with 10/01/2010 HCPCS changes; removed HCPCS S0146 deleted 09/30/2010.

Revised08/27/2009

MPTAC review.

Medically necessary coverage to include criteria for Hepatitis C Genotype 1 slow responders. Removed liver biopsy criteria from medically necessary statements. Clarified not medically necessary statements. Removed place of service. Definitions added, Appendix B removed, rationale and references updated.

Revised11/20/2008MPTAC review.  Medically Necessary coverage to include coverage for Hepatitis C Genotype 4 individuals who responded to initial therapy. Discussion and references updated.
 04/01/2008References updated to reflect change from USP DI to new DrugPoints compendia.
Reviewed11/29/2007MPTAC review. References updated.
Reviewed08/23/2007MPTAC review. Coding updated. References updated.
Revised09/14/2006MPTAC review. Added increase in medically necessary treatment period for up to 48 weeks for Hepatitis C (HCV) Genotype 2 or 3 in individuals who have had no response to prior therapy or who have relapsed; and for Hepatitis C (HCV) individuals (all genotypes) co-infected with stable human immunodeficiency virus (HIV). Added: Liver biopsy no longer required if contraindicated or not warranted in the treating physician's judgment.
Reviewed06/08/2006MPTAC review. References updated. No change in guideline position.
New07/14/2005MPTAC initial guideline development.

 

 

Appendix A1

Testing for Hepatitis C