COMPARISON OF PEGYLATED INTERFERON (PEG IFN), LAMIVUDINE, ADEFOVIR, ENTECAVIR, TELBIVUDINE, AND TENOFOVIR THERAPY FOR CHRONIC HEPATITIS Ba
| Feature | PEG IFNb | Lamivudine | Adefovir | Entecavir | Telbivudine | Tenofovir |
|---|---|---|---|---|---|---|
| Route of administration | Subcutaneous injection | Oral | Oral | Oral | Oral | Oral |
| Duration of therapyc | 48-52 weeks | ≥52 weeks | ≥48 weeks | ≥48 weeks | ≥52 weeks | ≥48 weeks |
| Tolerability | Poorly tolerated | Well tolerated | Well tolerated; creatinine monitoring recommended | Well tolerated | Well tolerated | Well tolerated; creatinine monitoring recommended |
| HBeAg seroconversion | ||||||
1 yr Rx >1 yr Rx | 18-20% NA | 16-18% up to 50% @ 5 yrs | 12% 43% @ 3 yrsd | 21% 31% @ 2 yrs 44% @ 6 yrs | 22% 30% @ 2 yrs | 21% 40% @ 5 yrs |
| Log10 HBV DNA reduction (mean copies/mL) | ||||||
HBeAg-reactive HBeAg-negative | 4.5 4.1 | 5.5 4.4-4.7 | median 3.5-5 median 3.5-3.9 | 6.235.0 | 6.4 5.2 | 6.2 4.6 |
| HBV DNA PCR negative (<300-400 copies/mL; <1000 copies/mL for adefovir) at end of yr 1 | ||||||
HBeAg-reactive HBeAg-negative | 10-25% 63% | 36-44% 60-70% | 13-21% 48-77% | 67% (91% @ 4 yrs) 90% | 60% 88% | 76% 93% |
| ALT normalization at end of yr 1 | ||||||
HBeAg-reactive HBeAg-negative | 39% 34-38% | 41-75% 62-79% | 48-61% 48-77% | 68% 78% | 77% 74% | 68% 76% |
HBsAg loss yr 1 >yr 1 | 3-4% 12% 5 yr after 1 yr of Rx | ≤1% No data | 0% 5% at yr 5 | 2% 6% at yr 6 | <1% No data | 3% 8% at yr 5 |
| Histologic improvement (≥2 point reduction in HAI) at yr 1 | ||||||
HBeAg-reactive HBeAg-negative | 38% 6 months after 48% 6 months after | 49-56% 61-66% | 53-68% 64% | 72% 70% | 65% 67% | 74% 72% |
| Viral resistance | None | 15-30% @ 1 yr 70% @ 5 yrs | None @ 1 yr 29% @ 5 yrs | ≤1% @ 1 yre 1.2% @ 6 yrse | Up to 5% @ yr 1 Up to 22% @ yr 2 | 0% @ yr 1 0% through yr 5 |
| Pregnancy category | C | Cf | C | C | B | B |
| Cost (US$) for 1 yr | ~$18,000 | ~$2,500 | ~$6,500 | ~$8,700g | ~$6,000 | ~$6,000 |
aGenerally, these comparisons are based on data on each drug tested individually versus placebo in registration clinical trials; because, with rare exception, these comparisons are not based on head-to-head testing of these drugs, relative advantages and disadvantages should be interpreted cautiously.
bAlthough standard interferon α administered daily or three times a week is approved as therapy for chronic hepatitis B, it has been supplanted by PEG IFN, which is administered once a week and is more effective. Standard interferon has no advantages over PEG IFN.
cDuration of therapy in clinical efficacy trials; use in clinical practice may vary.
dBecause of a computer-generated randomization error that resulted in misallocation of drug versus placebo during the second year of clinical trial treatment, the frequency of HBeAg seroconversion beyond the first year is an estimate (Kaplan-Meier analysis) based on the small subset in whom adefovir was administered correctly.
e7% during a year of therapy (43% at year 4) in lamivudine-resistant pts.
fDespite its Class C designation, lamivudine has an extensive pregnancy safety record in women with HIV/AIDS.
gApproximately $17,400 for lamivudine-refractory pts.
Abbreviations: ALT, alanine aminotransferase; HAI, histologic activity index; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; NA, not applicable; PEG IFN, pegylated interferon; Rx, therapy; yr, year.