response in adult patients with compensated liver disease who were treatment naïve or had relapsed following therapy with alpha interferon alone; pediatric patients previously untreated with alpha interferon experienced a sustained virologic response. See REBETOL package insert for additional information.
Chronic Hepatitis B
Adults
The safety and efficacy of INTRON A in the treatment of chronic hepatitis B were eva luated in three clinical trials in which INTRON A doses of 30 to 35 million IU per week were administered subcutaneously (SC), as either 5 million IU daily (QD), or 10 million IU three times a week (TIW) for 16 weeks vs no treatment. All patients were 18 years of age or older with compensated liver disease, and had chronic hepatitis B virus (HBV) infection (serum HBsAg positive for at least 6 months) and HBV replication (serum HBeAg positive). Patients were also serum HBV-DNA positive, an additional indicator of HBV replication, as measured by a research assay.7,8 All patients had elevated serum alanine aminotransferase (ALT) and liver biopsy findings compatible with the diagnosis of chronic hepatitis. Patients with the presence of antibody to human immunodeficiency virus (anti-HIV) or antibody to hepatitis delta virus (anti-HDV) in the serum were excluded from the studies.
Virologic response to treatment was defined in these studies as a loss of serum markers of HBV replication (HBeAg and HBV DNA). Secondary parameters of response included loss of serum HBsAg, decreases in serum ALT, and improvement in liver histology.
In each of two randomized controlled studies, a significantly greater proportion of INTRON A-treated patients exhibited a virologic response compared with untreated control patients (see TABLE 3). In a third study without a concurrent control group, a similar response rate to INTRON A therapy was observed. Pretreatment with prednisone, eva luated in two of the studies, did not improve the response rate and provided no additional benefit.
The response to INTRON A therapy was durable. No patient responding to INTRON A therapy at a dose of 5 million IU QD or 10 million IU TIW relapsed during the follow-up period, which ranged from 2 to 6 months after treatment ended. The loss of serum HBeAg and HBV DNA was maintained in 100% of 19 responding patients followed for 3.5 to 36 months after the end of therapy.
In a proportion of responding patients, loss of HBeAg was followed by the loss of HBsAg. HBsAg was lost in 27% (4/15) of patients who responded to INTRON A therapy at a dose of 5 million IU QD, and 35% (8/23) of patients who responded to 10 million IU TIW. No untreated control patient lost HBsAg in these studies.
In an ongoing study to assess the long-term durability of virologic response, 64 patients responding to INTRON A therapy have been followed for 1.1 to 6.6 years after treatment; 95% (61/64) remain serum HBeAg negative, and 49% (30/61) lost serum HBsAg.
INTRON A therapy resulted in normalization of serum ALT in a significantly greater proportion of treated patients compared to untreated patients in each of two controlled studies (see TABLE 4). In a third study without a concurrent control group, normalization of serum ALT was observed in 50% (12/24) of patients receiving INTRON A therapy.
Virologic response was associated with a reduction in serum ALT to normal or near normal (≤1.5 × the upper limit of normal) in 87% (13/15) of patients responding to INTRON A therapy at 5 million IU QD, and 100% (23/23) of patien
