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Telaprevir, Boceprevir for HCV: High Cost may warrant 'criteria for use' policies
By Brenda Le, Pharmacy Department Volunteer at Santa Clara Valley Medical Center.
Paul Hsiao, Pharm D, Pharmacist Specialist in the Purchasing Division of the Santa Clara Valley Medical Center Department of Pharmacy.
Jessica C. Song, M.A., Pharm.D, Clinical Supervisor of Pharmacy and Therapeutics, Ambulatory Care, and Mental Health at Santa Clara Valley Medical Center, San Jose, CA, is Associate Editor for Infectious Disease Alert.
Brenda Le, Paul Hsiao and Jessica C. Song report no financial relationships relevant to this field of study.
Hepatitis C virus (HCV) associated liver disease has affected an estimated 180 million people worldwide, and it continues to be the most common indication for liver transplantation.1 Of the 6 major HCV genotypes, HCV genotype 1 is the most common strain responsible for infections in North America, South America, and Europe.1 Chronic HCV patients have a 15% to 30% chance of progressing to cirrhosis over the ensuing 3 decades. Moreover, cirrhotic HCV patients are at heightened risk for hepatocellular carcinoma, which occurs at a rate of 1% to 3% per year.1
An updated clinical practice guideline for chronic HCV infection was recently developed by the American Association for the Study of Liver Diseases (AASLD).2 Prior to the publication of the 2011 AASLD guideline for chronic HCV infection, the standard of care for genotype 1 patients was the combination of peginterferon alfa-2a or peginterferon alfa-2b and weight-based ribavirin, administered for 48 weeks.32 In the updated guideline, the working group recommended the addition of boceprevir, a newly FDA approved NS3/4A protease inhibitor, to peginterferon alfa and weight-based ribavirin after a 4-week lead-in treatment phase of peginterferon alfa/ribavirin in treatment-naïve patients. The duration of treatment depends on the patient's HCV-RNA results at treatment weeks 8,12, and 24; boceprevir treatment duration ranges from 24 to 44 weeks.
For treatment-experienced patients (prior-relapse, partial-responder), the FDA label4 and the updated AASLD guideline2 recommends the addition of boceprevir to peginterferon alfa and weight-based ribavirin, following a 4-week lead in treatment period, with triple drug therapy lasting from 32 to 44 weeks. Cirrhotic patients require 44 weeks of triple therapy, following 4 weeks of dual therapy with peginterferon alfa and ribavirin. Treatment cessation of all three drugs should be considered if the patient's HCV RNA level exceeds 100 IU/mL at week 12 or week 24.2
The 2011 AASLD guideline also recommends the use of another FDA-approved NS3/4A protease inhibitor, telaprevir, for use in genotype 1 HCV patients (treatment naïve and experienced).2 Unlike boceprevir-treated patients, patients placed on telaprevir do not require a 4-week lead in period. Telaprevir should be used in combination with peginterferon alfa and ribavirin for 12 weeks in both treatment naïve and treatment experienced patients. Of note, telaprevir can be considered for use in prior null responders to a course of dual therapy with peginterferon alfa and weight-based ribavirin.2 Upon completion of 12 weeks of triple drug therapy, dual therapy with peginterferon alfa and weight-based ribavirin needs to be continued for an additional 12 to 36 weeks, depending on HCV-RNA levels at weeks 4 and/or 12, cirrhosis status, along with prior treatment history.2,5 Patients who display HCV RNA levels in excess of 1000 IU/mL at treatment weeks 4 or 12 should consider discontinuing all three drugs.2 With the inclusion of the new protease inhibitors in evidence-based treatment guidelines, formulary decision makers have many factors to consider in developing a strategy for ensuring cost-effective management of genotype 1 HCV patients. Increased drug costs, adherence, adverse effects, and appropriate utilization management are critical issues faced by institutions considering the addition of protease inhibitors to formularies. This article will review cost considerations associated with adding boceprevir or telaprevir to peginterferon alfa/weight-based ribavirin regimens for genotype 1 HCV patients.
Formulations, Adverse Effects, Acquisition Costs
Boceprevir is marketed in the U.S. as a 200 mg capsule, priced at $9.06/capsule, and telaprevir is available as a 375 mg tablet, priced at $75.07/tablet.4,5 The pill burden of boceprevir might prove burdensome for some chronic hepatitis C patients, since patients will require 12 capsules a day to meet the recommended dose of 800 mg every 7 to 9 hours.4 Patients receiving telaprevir will face a lower pill burden, since the dosing regimen of 750 mg every 7-9 hours would require the ingestion of six tablets per day.5 A 24-week treatment course of boceprevir would cost $18,264.96 and longer treatment courses of 32 weeks to 44 weeks would increase the cost to $24,353.28 and $33,485.76, respectively. A 12-week treatment course of telaprevir would cost $37,835.28.
At Santa Clara Valley Medical Center (San Jose, CA), an estimated 30 to 60 patients will require the addition of boceprevir or telaprevir to peginterferon alfa and weight-based ribavirin in 2012. The estimated cost impact will range from $1,135,058 to $2,270,117 for the addition of telaprevir to the standard dual therapy regimen of peginterferon alfa and weight-based ribavirin. The projected financial impact of adding boceprevir to peginterferon alfa and weight-based ribavirin will depend on treatment duration. The costs of treating 30 to 60 patients with boceprevir for 24 weeks, 32 weeks, and 44 weeks will range from $547,948.80 to $1,095,897.60; $779,304.96 to $1,558,609.92; and $1,473,373.44 to $2,946,746.88, respectively.
Additional costs will be incurred in the management of anemia that may result from the use of boceprevir or telaprevir. Anemia occurred in 43% to 49% of boceprevir-treated patients in Phase III trials, compared with 20% to 29% of patients who received dual therapy regimens consisting of peginterferon alfa and weight-based ribavirin.6,7 In the SPRINT-2 trial, patients qualified for the use of once weekly subcutaneous injections of erythropoietin 40,000 units if their serum hemoglobin levels dropped to a level of 10 g/dL or lower.6 Forty-three percent of boceprevir-treated patients required erythropoietin therapy, with mean durations of 94 weeks and 156 weeks in response-guided subjects and fixed-duration subjects, respectively. Nearly 1 in 4 dual therapy (peginterferon alfa and weight-based ribavirin) patients required erythropoietin, with a mean duration of 121 weeks. The cost of once weekly erythropoietin 40,000 units at Santa Clara Valley Medical Center approaches $394. Assuming a percentage increase of 20% for anemia rates in boceprevir-treated patients versus peginterferon-ribavirin-treated patients, the additional cost of using erythropoietin in 6 to 12 patients (20% of 30 to 60 patients) would range from $222,216 to $444,432 (treatment duration of 94 weeks). Study investigators of the REALIZE and ADVANCE studies did not use erythropoietin for the management of anemia in study patients, but reduced ribavirin doses if warranted.8,9 Anemia occurred in 37% to 39% of telaprevir-treated patients and in 19% to 22% of placebo-treated patients.
The addition of telaprevir or boceprevir to the combination of peginterferon alfa and weight-based ribavirin will bring substantial new pharmacy costs to the management of chronic genotype 1 HCV patients. Institutions will likely resort to utilizing "criteria for use" policies that will ensure that appropriate patients will receive these vital, but expensive medications.10 Coverage criteria should consider the following factors:
(1) exclusion criteria (with special emphasis on checking for non-adherence to prior medications),
(2) inclusion criteria,
(3) limiting prescriptions to a 28-day supply,
(4) treatment duration,
(5) recommended monitoring,
(6) use in specific populations,
(7) drug interactions,
(8) patient education.
County institutions with Medication Assistance Programs may minimize the costs associated with stocking such expensive medications by maintaining a non-formulary status for the drugs. Following approval of non-formulary drug requests, the necessary paperwork required for medication assistance will be submitted by prescribers and patients prior to the dispensing of boceprevir or telaprevir. Despite the great advancement in hepatitis C treatment, the significant pill burden, adverse effect profile, and exorbitant cost of protease inhibitors will necessitate the implementation of appropriate utilization management strategies by institution decision makers.