Drug Class Monograph

Transcription

1 Drug Class Monograph Class: Chronic Hepatitis B Drug: Baraclude (entecavir), Epivir (lamivudine), Hepsera (adefovir), Intron A (interferon alfa- 2b), Pegasys (peginterferon alfa-2a), Tyzeka (telbivudine), Viread (tenofovir) Line of Business: Non-Medicare Effective Date: November 16, 2016 Renewal Date: November 16, 2016 This policy has been developed through review of medical literature, consideration of medical necessity, generally accepted medical practice standards, and approved by the IEHP Pharmacy and Therapeutics Subcommittee. Policy/Criteria: 1. Adefovir, Entecavir, Lamivudine, Tyzeka (telbivudine) a. Confirmed diagnosis of chronic hepatitis B infection; i. Prescribed by IEHP Hepatitis Center of Excellence specialist; AND ii. One of the following: Elevation in alanine aminotransferase (ALT >2 ULN); Documentation of significant histological disease (e.g. Significant inflammation and/or fibrosis in biopsy); iii. Formulary position: Entecavir is the preferred hepatitis B agent. Note: Tenofovir is considered DHCS carve-out. b. Requests for treatment of acute symptomatic hepatitis B will be reviewed by the IEHP pharmacist; i. Only indicated for patients with fulminant hepatitis B defined by two of the following: hepatic encephalopathy, serum bilirubin > 10.0 mg/dl or INR > 1.6; ii. Must be prescribed by IEHP Hepatitis Center of Excellence specialist. 2. Intron A (interferon alfa-2b) a. Confirmed diagnosis of chronic hepatitis B infection; i. Prescribed by IEHP Hepatitis Center of Excellence specialist; AND ii. One of the following: Elevation in alanine aminotransferase (ALT >2 ULN); Documentation of significant histological disease (e.g. Significant inflammation and/or fibrosis in biopsy);

2 iii. Formulary position: Entecavir is the preferred hepatitis B agent. b. Confirmed diagnosis of chronic hepatitis C infection; i. Please refer to the Chronic Hepatitis C Drug Class Monograph. c. Confirmed diagnosis of malignant indication; i. Please refer to the Antineoplastic Drug Class Monograph. d. Confirmed diagnosis of condylomata acuminata; i. Failure or clinically significant adverse effects to all of the alternatives: imiquimod 5% cream and podofilox; ii. Prescribed by an infectious disease specialist. 3. Pegasys (peginterferon alfa-2a) a. Confirmed diagnosis of chronic hepatitis B infection; i. Prescribed by IEHP Hepatitis Center of Excellence specialist; AND ii. One of the following: Elevation in alanine aminotransferase (ALT >2 ULN); Documentation of significant histological disease (e.g. Significant inflammation and/or fibrosis in biopsy); iii. Formulary position: Entecavir is the preferred hepatitis B agent. b. Confirmed diagnosis of chronic hepatitis C infection; i. Please refer to the Chronic Hepatitis C Drug Class Monograph. Clinical Justification: AASLD Guidelines for Treatment of Chronic Hepatitis B 2015 Treatment of Persons with Immune-Active CHB The AASLD recommends antiviral therapy for adults with immune-active CHB (HBeAg negative or HBeAg positive) to decrease the risk of liver-related complications. Immune-active CHB is defined by an elevation of ALT >2 ULN or evidence of significant histological disease plus elevated HBV DNA above 2000 IU/mL (HBeAg negative) or above 20,000 IU/mL (HBeAg positive). The AASLD recommends Peg-INF, entecavir, or tenofovir as preferred initial therapy for adults with immune-active CHB. Head-to-head comparisons of antiviral therapies fail to show superiority of one therapy over another in achieving risk reduction in liver-related complications. However, in recommending Peg-IFN, tenofovir, and entecavir as preferred therapies, the most important factor considered was the lack of resistance with long-term use. Patientspecific factor that need to be considered in choosing between Peg-IFN, entecavir, and tenofovir include: o Desire for finite therapy; o Anticipated tolerability of treatment side effects; o Comorbidities: Peg-IFN is contraindicated in persons with autoimmune disease, uncontrolled psychiatric disease, cytopenias, severe cardiac disease, uncontrolled seizures, and decompensated cirrhosis.

3 o Previous history of lamivudine resistance (entecavir is not preferred in this setting). o Family planning: A finite therapy with Peg-IFN pre-pregnancy or use of oral antiviral that is safe in pregnancy is best. o HBV genotype: A and B genotype are more likely to achieve HBeAg and HBsAg loss with Peg-IFN than non-a/b genotypes. o Medication costs. Peg-IFN is preferred over nonpegylated forms for simplicity. For persons treated with Peg-IFN, 48 weeks duration is used in most studies and is preferred. This treatment duration yields HBeAg seroconversion rates of 20%-31% and sustained off-treatment HBV DNA suppression <2000 IU/mL in ~65% of persons who achieve HBeAg to anti-hbe seroconversion. The combination of Peg-IFN and NAs has not yielded higher rates of off-treatment serological or virological responses and is not recommended. Duration of therapy for NA-based therapy is variable and influenced by HBeAg status, duration of HBV DNA suppression, and presence of cirrhosis/decompensation. All NAs require dose adjustment in persons with creatinine clearance <50 ml/min. Evaluation for stage of disease using noninvasive methods or liver biopsy is useful in guiding treatment decisions including duration of therapy. Treatment with antivirals does not eliminate the risk of HCC, and surveillance for HCC should continue in persons who are at risk. Additional factors included in the decision to treat persons with immune-active CHB but ALT<2 ULN and HBV DNA below thresholds are: o Age: Older age (40 years) is associated with higher likelihood of significant histological disease; o Family history of HCC; o Previous treatment history: Serological benefit of Peg-IFN (HBeAg and HBsAg loss) may occur months to years after treatment discontinuation (delayed). Previous NA exposure is a risk for drug resistance. o Presence of extrahepatic manifestations: indication for treatment independent of liver disease severity. Treatment of Adults with Immune-Tolerant CHB The AASLD recommends against antiviral therapy for adults with immune-tolerant CHB; o Immune-tolerant status should be defined by ALT levels utilization 30 U/L for men and 19 U/L for women as ULNs rather than local laboratory ULNs. The AASLD suggests antiviral therapy in the select group of adults >40 years of age with normal ALT and elevated HBV DNA ( 1,000,000 IU/mL) and liver biopsy showing significant necroinflammation or fibrosis. Renal and Bone Disease in Persons on NA Therapy

4 The AASLD suggests no preference between entecavir and tenofovir regarding potential long-term risks of renal and bone complications. o The existing studies do not show significant differences in renal dysfunction, hypophosphatemia or bone mineral density between HBV-infected persons treated with tenofovir or entecavir. However, renal events, such as acute renal failure or hypophosphatemia, have been reported in tenofovir-treated persons. o In cases of suspected tenofovir-associated renal dysfunction and/or osteoporosis/osteomalacia, tenofovir should be discontinued and substituted with an alternate NA with consideration for previous drug resistance. o Dosage of NAs should be adjusted based on renal function and creatinine clearance, as recommended by manufacturers. Management of Persons with Persistent Low-Level Viremia on NA Therapy The AASLD suggests that persons with persistent low-level viremia (<2000 IU/mL) on entecavir or tenofovir monotherapy continue monotherapy, regardless of ALT. The AASLD suggests one of two strategies in persons with virological breakthrough on entecavir or tenofovir monotherapy: either switch to another antiviral monotherapy with high barrier to resistance or add a second antiviral drug that lacks cross-resistance. Management of Adults with Cirrhosis and Low-Level Viremia The AASLD suggests that adults with compensated cirrhosis and low levels of viremia (<2000 IU/mL) be treated with antiviral therapy to reduce the risk of decompensation, regardless of ALT level. Tenofovir and entecavir are preferred because of their potency and minimal risk of resistance. Antivirals with a low genetic barrier to resistance should not be used because the emergence of resistance can lead to decompensation. Peg-IFN is not contraindicated in persons with compensated cirrhosis but NAs are safer. AASLD Guidelines for Chronic Hepatitis B 2009 Recommendations for Treatment of Patients with Acute Symptomatic Hepatitis B Treatment is only indicated for patients with fulminant hepatitis B and those with protracted, severe acute hepatitis B. Lamivudine or telbivudine may be used when the anticipated duration of treatment is short; otherwise, entecavir is preferred. Treatment should be continued until HBsAg clearance is confirmed or indefinitely in those who undergo liver transplantation. IFN-alpha is contraindicated.

5 AASLD Guidelines for Treatment of Chronic Hepatitis B 2015

6 AASLD Guidelines for Treatment of Chronic Hepatitis B 2015 AASLD Guidelines for Treatment of Chronic Hepatitis B 2015

7 Centers for Disease Control and Prevention: Sexually Transmitted Disease Treatment Guidelines 2010 Regimens Treatment of genital warts should be guided by the preference of the patient, available resources, and the experience of the health-care provider. No definitive evidence suggests that any of the available treatments are superior to any other, and no single treatment is ideal for all patients or all warts. The use of locally developed and monitored treatment algorithms has been associated with improved clinical outcomes and should be encouraged. Because of uncertainty regarding the effect of treatment on future transmission of HPV, and the possibility of spontaneous resolution, an acceptable alternative for some persons is to forego treatment and wait for spontaneous resolution. Factors that influence selection of treatment include wart size, wart number, anatomic site of the wart, wart morphology, patient preference, cost of treatment, convenience, adverse effects and provider experience. Factors that might affect response to therapy include the presence of immunosuppression and compliance with therapy, which can consist of either a single treatment or complete course of treatment. Treatment regimens are classified into patient-applied and provider-applied modalities. Patient-applied modalities are preferred by some patients because they can be administered in the privacy of the patient s home. To ensure that patient-applied modalities are effective, patients must comply with the treatment regimen and must be capable of identifying and reaching all genital warts.

8 References: 1. Lok AS, McMahon BJ. American Association for the Study of Liver Diseases (AASLD) Practice Guideline Update. Chronic Hepatitis B: update Hepatology Sep;50(3): Prescribing Information: Baraclude. Bristol-Myers Squibb Company, Princeton, NJ May Prescribing Information: Hepsera. Gilead Sciences, Inc, Foster City, CA November Prescribing Information: Pegasys. Roche Pharmaceuticals, Nutley, New Jersey October Prescribing Information: GlaxoSmithKline, Research Triangle Park, NC December Prescribing Information: Viread. Gilead Sciences, Inc, Foster City, CA October Prescribing Information: Tyzeka. Novartis Pharmaceuticals Corporation, New Jersey, January Terrault, NA, Bzowej NH, et al. American Association for the Study of Liver Diseases (AASLD) Guidelines for Treatment of Chronic Hepatitis B. Hepatology, Vol. 00, No. 00, Sexually Transmitted Disease Treatment Guidelines 2010, Centers for Disease Control and Prevention. Available at: Accessed October 11, 2016.