Improvement in liver histology was eva luated in Studies 1 and 3 by comparison of pretreatment and 6-month posttreatment liver biopsies using the semiquantitative Knodell Histology Activity Index.9 No statistically significant difference in liver histology was observed in treated patients compared to control patients in Study 1. Although statistically significant histological improvement from baseline was observed in treated patients in Study 3 (P≤0.01), there was no control group for comparison. Of those patients exhibiting a virologic response following treatment with 5 million IU QD or 10 million IU TIW, histological improvement was observed in 85% (17/20) compared to 36% (9/25) of patients who were not virologic responders. The histological improvement was due primarily to decreases in severity of necrosis, degeneration, and inflammation in the periportal, lobular, and portal regions of the liver (Knodell Categories I + II + III). Continued histological improvement was observed in four responding patients who lost serum HBsAg and were followed 2 to 4 years after the end of INTRON A therapy.10

Pediatrics
The safety and efficacy of INTRON A in the treatment of chronic hepatitis B was eva luated in one randomized controlled trial of 149 patients ranging from 1 year to 17 years of age. Seventy-two patients were treated with 3 million IU/m2 of INTRON A therapy administered subcutaneously three times a week (TIW) for 1 week; the dose was then escalated to 6 million IU/m2 TIW for a minimum of 16 weeks up to 24 weeks. The maximum weekly dosage was 10 million IU TIW. Seventy-seven patients were untreated controls. Study entry and response criteria were identical to those described in the adult patient population.

Patients treated with INTRON A therapy had a better response (loss of HBV DNA and HBeAg at 24 weeks of follow-up) compared to the untreated controls (24% [17/72] vs 10% [8/77] P=0.05). Sixteen of the 17 responders treated with INTRON A therapy remained HBV DNA and HBeAg negative and had a normal serum ALT 12 to 24 months after completion of treatment. Serum HBsAg became negative in 7 out of 17 patients who responded to INTRON A therapy. None of the control patients who had an HBV DNA and HBeAg response became HBsAg negative. At 24 weeks of follow-up, normalization of serum ALT was similar in patients treated with INTRON A therapy (17%, 12/72) and in untreated control patients (16%, 12/77). Patients with a baseline HBV DNA <100 pg/mL were more likely to respond to INTRON A therapy than were patients with a baseline HBV DNA >100 pg/mL (35% vs 9%, respectively). Patients who contracted hepatitis B through maternal vertical transmission had lower response rates than those who contracted the disease by other means (5% vs 31%, respectively). There was no evidence that the effects on HBV DNA and HBeAg were limited to specific subpopulations based on age, gender, or race.

TABLE 1 RESPONSE BY BASELINE CD4 COUNT* IN AIDS-RELATED KS PATIENTS  30 million IU/m2
TIW, SC and 35 million IU QD, SC
 Asymptomatic Symptomatic
*
Data for CD4, and asymptomatic and symptomatic classification were not available for all patients. 
CD4<200 4/14 (29%) 0/19 (0%)
200≤CD4≤400 6/12 (50%) 0/5 (0%)
  } 58% 
CD4>400 5/7 (71%) 0/0 (0%)
TABLE 2 SUSTAINED ALT RESPONSE RATE VS DURATION OF THERAPY IN CHRONIC HEPATITIS C PATIENTS INTRON A 3 Million IU TIW  Treatment Group*- Number of Patients (%)