Cost-effectiveness of Pegylated Interferon Treatments for

Chronic Hepatitis C (HCV) Patients in Canada

Piwko C, PhD1, Walker JH, PhD1,2, Iskedjian M, MSc1, Einarson TR, PhD1,3
1
PharmIdeas Research and Consulting Inc., Oakville, Ontario, 2Faculty of Business, Brock University, St. Catharines, Ontario, 3Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario

Table 2. Clinical Trial SVR Values used for Comparisons. Table 5. Sensitivity Analysis with SVR Parameter Value biasing against Pegetron.
Objective
• To compare the cost-effectiveness of the Interferon-based regimens available in Canada for Proportion of Patients with Product SVR Rate Incremental SVR Cost Incremental Cost Results
Product
the management of patients with Chronic Hepatitis C Virus (HCV), genotype 1, that have been Sustained Viral Response
reported in a number of multicenter trials. Rebetron 36% $14,612
Pegasys RBV 46%2
Pegasys RBV 46% 10% $16,293 $1,681 Dominated
Background Rebetron 36% 2

4
Pegetron 48% Pegetron 48% 2% $15,469 ($824) Cost Effective
• Current HCV treatment combinations include
Rebetron 34%4
- Interferon alfa-2b plus ribavirin (Rebetron®)
Sensitivity Analysis of Patient Weight Distribution
- Pegylated interferon alfa-2b plus ribavirin (Pegetron®) Table 3. Product Cost.
- Pegylated interferon alfa-2a plus ribavirin (Pegasys RBV®) • Cost neutrality of Pegetron in comparison to Pegasys RBV was not obtained. Even when all
patients are assumed weighing 75 kg or more with the SVRs and the EVRs being held constant,
• Randomized phase III trials have compared Rebetron both with Pegetron and with Pegasys Product
Cost per Week
Patient Weight
Cost per Week
Patient Weight Average Costa Average Cost for 48 Pegetron was still dominant by $85.
RBV. per Week Weeksb
< 75 kg > 75 kg
Dosing Regimens Conclusions
Pegasys RBV $395.84 $395.84 $395.84 $16,293
• Rebetron: Recommended dosage is 3 million IU of interferon alfa-2b 3 times per week via
subcutaneous injection plus ribavirin capsules, depending on patient’s weight, 1000 mg daily Pegetron $376.10 $415.59 $396.63 $15,469 • These results indicate that treatment with Pegetron maximizes the cost-effectiveness for
(< 75 kg) or 1200 mg daily (>75 kg). the management of patients with Chronic Hepatitis C Virus. Pegetron is a good predictor of
Rebetron $376.10 $415.59 $396.63 $14,612 sustained viral response, what allows discontinuation of treatment in those patients unlikely
• Pegetron: Based on the results of the clinical trial, the recommended dose of peginterferon aAverage Price is 48% X (price for < 75kg) + 52% X (price for >75 kg)
alfa-2b is 1.5 μg/kg/week subcutaneous in combination with ribavirin capsules. The dose of to respond with further therapy. These results indicate that Pegetron dominates Pegasys RBV
bAverage product cost is (1-EVR%) X 12 weeks X Average Cost per week + EVR% X 48 weeks X Average Cost per week
ribavirin to be used in combination with peginterferon alfa-2b is based on patient body weight: in the base case analysis and is cost effective in the sensitivity analyses. In particular, assuming
800 mg per day (<64 kg); 1000 mg per day (64-75kg); and 1200 mg per day (>75 kg). Sensitivity Analyses that the SVR is the same both for Pegetron and for Pegasys RBV, it shows that unless the 48-
week treatment cost is reduced by $824 for Pegasys RBV, Pegetron is the less costly alternative
• Pegasys RBV: Recommended dosage is 180 µg of pegylated interferon alfa-2a per week via • Two sensitivity analyses were performed. In the first sensitivity analysis, it was assumed that therapy for Chronic Hepatitis C treatment.
subcutaneous injection, plus ribavirin dosed as 1000 mg per day (<75 kg) or 1200 mg per day the Rebetron SVR rate from the Fried et al. trial was the same rate as in the Manns et al. trial.
(>75 kg). This was the worst case for Pegetron, since the SVR rate from the Manns et al. trial is lower. In
• Clinical use of these medications suggests that, unless early viral response (EVR) is seen at 12 the second sensitivity analysis, a threshold analysis was done on the average weekly price of Limitations
weeks, therapy should not be continued for eventual nonresponders. EVR is defined as >2log10 Pegetron compared to Pegasys RBV.
• Since there is no head to head comparison of Pegetron and Pegasys RBV, data from two clinical
decline in HCV RNA levels from baseline by week 12, and SVR (sustained viral response) as no trials comparing these two products to Rebetron was used. The two clinical trials from which
detectable HCV RNA level at the end of treatment and again 24 weeks after completing of Results SVR data were taken, do not provide information on the EVR, hence the SVR data are based on
treatment. • Evaluating EVR leads to lower overall treatment cost for Rebetron and Pegetron than Pegasys the starting cohorts. Further studies are warranted from more comprehensive perspectives.
RBV. In all scenarios Pegetron was dominant over Pegasys RBV, with a lower expected treatment
Methods cost and a higher chance of achieving a SVR. Updated results are presented below. References
• A decision analysis model was constructed to compare Pegetron and Pegasys RBV at approved Table 4. Base Case Comparisons.
1. Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus
ribavirin in patients with chronic hepatitis C. Hepatology, 2003;38:645-652.
label doses. Data for the cost-effectiveness analysis were derived from the literature and the 2. Fried MW, Shiffman ML, Reddy KR, Smith C, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med,
time horizon was 48 weeks. Perspective was that of the Provincial Formulary Reimbursement 2002;347:975-982.
Trial Product SV Rate Incremental SVR Cost Incremental Cost 3. Ferenci P, Shiffman ML, Fried MW, et al. Early prediction of response to 40 KDA Peginterferon Alfa-2a (Pegasys®) Plus Ribavirin (RBV) in
plans. Product prices used were current Canadian wholesale drug prices, no provincial markups patients with Chronic Hepatitis C. Hepatology, 2001; 34(4) Pt/ 2, 351A.
or dispensing fees added. 4. Manns MP, McHutchison JG, Gordon SC et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial
Rebetron 36% $14,612 treatment of chronic hepatitis C: a randomized trial. Lancet 2001;358:958–65.
• In the base case, it was assumed that 48% of the patients weigh less than 75 kg5. The length Fried 5. Statistics Canada. National Population Health Survey (1996-97), 1997.
of therapy reflected the current treatment algorithm for HCV genotype 1 patients. Initially, Pegasys RBV 46% 10% $16,293 $1,681
6. Wong JB, Davis GL, McHutchison JG, Albrecht JK et al. Clinical implications of testing viral response during ribavirin and peginterferon
alfa-2b treatment for chronic hepatitis C. Hepatology, (53rd Ann. Mtg. Am. Assoc. Study Liver Dis., AASLD, Boston, MA, USA, Nov. 1-5, 2002),
patients receive 12 weeks of therapy and for those patients having an acceptable EVR, therapy Rebetron 34% $14,612 Vol. 36, No. 4, Pt. 2 of 2, Oct., 2002, Abstr. No. 472
is continued for an additional 36 week. Hence, they receive therapy for 48 weeks. Manns
Pegetron 48% 14% $15,469 $857
Table 1. Clinical Trial EVR Values used for Comparisons.
• Assuming that all parameters are equivalent in the two trials, Pegetron therapy shows a higher
Proportion of Patients with therapeutic response at a lower cost, and is hence dominant in comparison to Pegasys RBV.
Product
Early Viral Response

Pegasys RBV 81%3 Sensitivity Analysis

Pegetron 75%6 • In a sensitivity analysis assuming Rebetron rates were derived from the Fried trial (smaller Poster presented at Annual CAPT Meeting,
Rebetron 69%1 difference in SVR with Pegetron), and both Pegasys RBV and Pegetron being compared through Vancouver, BC, April 17, 2005.
Rebetron, we obtained dominance of Pegetron as illustrated in Table 5.
This study was sponsored by Schering Canada Inc.