Background information on Hepatitis C (HCV):
- 170 million people worldwide infected with HCV, 2.7 milllion people in U.S. infected
- 27% of worldwide cases of cirrhosis are due to HCV
- 25% of cases of hepatocellular carcinoma are due to HCV
- Established treatment with pegylated interferon (PEG IFN) and ribavirin have ~40% response rates in genotype 1 (74% of HCV in U.S.) and relapses are not uncommon among responders
New treatments for Hepatitis C (in combination with previous treatments):
- Two new drugs: Boceprevir (BOC) & Telaprevir (TVR)
- Overall sustained viral response (SVR) with BOC combination 63-66% vs 73-79% with TVR combination treatment
- Both trials demonstrate marked improvement over previous
- Mechanism of action: Protease inhibitor binding to NS3 HCV target
- BOC: Wholesale cost $1100/week (20-44 weeks)
- TVR: 12weeks cost: $49,000
Previous treatments for hepatitis C typically cost about $5000 per month (http://www.familydrugguide.com/family/ub/view/Consumer_Reports_Health/526033/4/hepatitis_c_drugs). The addition of these newer drugs could add another $50,000 to the cost of treatment. In some cases which respond well to the newer treatments, shorter treatment periods will lower the increase in cost. Although these drugs are expensive, they may be lifesaving and may obviate the need for liver transplantation. Due to the potential complications of HCV, more medications are in the pipeline. They may be easier to take but are likely to be expensive as well. The safety & effectiveness of these medications have not been demonstrated in published pediatric studies.
- Hepatology 2011; 54: 1433. Updated AASLD HCV treatment guidelines
- NEJM 2011; 364: 1195-206, Editorial pg. 1272. Addition of boceprevir, in 1097 previously untreated pts increased SVR. In whites, 40%–>67% & in blacks from 23% –>42%. Medication given after lead-in of 4 weeks. More frequent anemia in boceprevir-treated patients (SPRINT-2 study).Boceprevir dosing: 800mg (4 capsules) TID with food. (trying to space out doses evenly).
- NEJM 2011; 365: 1014. n=540. Telaprevir study: extended SVR 72%. In pts with rapid viral response (RVR) at 4 & 12 weeks (no detectable HCV), Telaprevir12weeksPegRbv24 was as effective as Telprevir12weeksPegRbv48. Dosing for study: Teleprevir 750mg TID, PEGalfa-2a 180mcg/wk, RBV1-1.2gm per day. Rash in 37% (severe in 5%), anemia in 39% (severe in 6%).
- NEJM 2011; 364: 2405, 2417, 2429 (review). Telaprevir addition: up to 75% response in HCV genotype 1 pts. n=1095 in 1st study, n=833 in 2nd study (re-treatment study)
- Gastroenterology 2011; 140: 746. Summary of results of boceprevir (used with IFN -alfa 2b 1.5/kg) & telaprevir (used with IFN -alfa 2a 180mcg). “Similar effectiveness” thus far. Telaprevir used for 12 weeks without lead-in period. TVR: most frequent problem -rash & then anemia. In practice, dosing in adults: Telaprevir will be used at 750mg TID in combination with IFN-2a 180mcg & RBV 1-1.2g/d. & used for 1st 12 weeks of Rx. This will allow ~50% of patients to have shorter Rx duration: if HCV RNA RVR –>24week total vs 48week total in those w/o RVR. Both drugs best for genotype 1.