Economic Burden and Current Managed Care Challenges Associated With Hepatitis C

Because peginterferon with ribavirin surpassed interferon plus ribavirin as the standard of therapy for the management of chronic HCV, it is of potentially greater interest to compare the cost-effectiveness of regimens containing peginterferon. An early review suggested that 6 of 7 (85.7%) studies had ICERs per QALY gained less than US$25,000 for peginterferon plus ribavirin versus interferon plus ribavirin, while 1 of those studies demonstrated cost savings, and another study demonstrated an ICER of $12,000 to $90,000 per QALY gained.¹¹ The authors of the study that did not demonstrate robust cost-effectiveness¹³ noted that the probability of chronic HCV patients developing cirrhosis over 30 years was 13% to 46% for men and 1% to 29% for women. The ICER of peginterferon with ribavirin was $26,000 to $64,000 per QALY gained for genotype 1, and $10,000 to $28,000 for other genotypes in men. For women, the ICER per QALY gained was $32,000 to $90,000 for genotype 1, and $12,000 to $42,000 for other genotypes. Improvements were found more in the form of health-related quality of life (HRQoL) gains than in prolonged survival. Thus, the cost per QALY was less than the cost per life-year.¹³ Since $100,000 per QALY gained is generally considered cost-effective, these findings indicate that peginterferon plus ribavirin is costeffective under a variety of clinical scenarios, but also highlights how patient and disease factors can change the success, and hence the cost-effectiveness, of therapy.

Another important factor in assessing the cost-effectiveness of peginterferon with ribavirin is the duration of therapy. Wong et al used a computer simulation to compare a 48-week course of peginterferon alfa-2b plus ribavirin with a potentially shorter course of peginterferon alfa-2b plus ribavirin, depending on the results of viral testing after 12 weeks of treatment.¹⁴ The assessment of 12-week rapid viral response (RVR) reduced the duration of antiviral treatment by 40% to 44% and antiviral costs by 44% to 45%, which corresponded to a savings of $15,116 to $16,268 for peginterferon plus ribavirin and $8300 for interferon plus ribavirin compared with 48-week dosing. The ICERs per discounted QALY gained were evaluated for a number of comparisons. Based on the 54% to 61% SVR rates from the study with peginterferon plus ribavirin, the expected extension of life expectancy was 3.6 years to 4 years, in general, and 5.9 years for patients with genotype 2 or 3. The 12-week evaluation demonstrated that peginterferon plus ribavirin had an ICER of $13,600 to $22,800 compared with interferon plus ribavirin. In the 24-week evaluation, peginterferon plus ribavirin had an ICER of $14,600 to $25,000 compared with interferon plus ribavirin. In patients with HCV genotype 1, the respective 12-week and 24-week ICERs were $13,500 to $19,300 and $15,100 to $20,600, relative to interferon plus ribavirin. In patients with genotype 2 or 3, the respective 12-week and 24-week ICERs were $15,400 to $47,100 and $15,100 to $46,700, due to the higher degree of efficacy of the interferon plus ribavirin regimen in that population. In these analyses, the lower range of the ICER was for weight-based ribavirin dosing, and the higher range was for ribavirin 800-mg fixed dosing, due to the greater efficacy of the weight-based regimen. These findings were mirrored in another study, which showed an increase in life expectancy of 4.3 years with peginterferon alfa-2b plus fixed-dose ribavirin, and 4.7 years with peginterferon alfa-2b plus weight-based ribavirin, as well as acceptable ICERs per QALY gained.15 The results demonstrated that peginterferon plus ribavirin may reduce liver complications, increase life expectancy, improve qualityadjusted life expectancy, and be cost-effective. In addition, monitoring could reduce the morbidity associated with the adverse effects of medication due to a shortened duration of therapy.^14,15

Management of adverse effects is an important consideration for cost-effectiveness of treatment. While it may be acceptable to reduce the duration of antiviral treatment when RVR is achieved, it is a less attractive option when viral response is not optimal. A common adverse effect of peginterferon plus ribavirin is anemia. Strategies for the management of anemia include reducing the dose of ribavirin or administering hematologic growth factors.^14,16 One study compared darbepoetin alpha, epoetin alpha, or ribavirin dose reduction for significant anemia (>3 g/dL reduction from baseline) in patients on standard doses of peginterferon alfa-2a or peginterferon alfa-2b with ribavirin 1200 mg per day for genotype 1, or standard doses of peginterferon alfa-2a or peginterferon alfa-2b with ribavirin 800 mg per day for genotypes 2 or 3. A Markov model was used to determine the cost-effectiveness of the hematologic growth factors. Dose reduction of ribavirin in patients with genotype 1 reduced SVR from 55.6% to 46.1%. Darbepoetin alpha increased costs by $14,100, and epoetin alpha by $24,600, compared with ribavirin dose reduction in the patients with genotype 1. The ICERs for darbepoetin alpha and epoetin alpha were $34,793 and $60,600 per QALY, respectively, relative to ribavirin dose reduction for genotype 1. Dose reduction of ribavirin in patients with genotype 2 or 3 reduced the SVR rate from 83.3% to 78.6%. The addition of darbepoetin alpha increased costs by $7000, and epoetin alpha increased costs by $13,200 compared with ribavirin dose reduction for patients with genotypes 2 and 3. For genotypes 2 and 3, the ICERs for darbepoetin alpha and epoetin alpha were $33,832 and $64,311 per QALY, respectively, relative to ribavirin dose reduction. These results suggest that administration of a hematologic growth factor, particularly darbepoetin alpha, rather than ribavirin dose reduction for anemia associated with HCV treatment, preserves efficacy and is cost-effective.¹⁶