The interferons are a family of
naturally occurring small proteins and glycoproteins with molecular weights of
approximately 15,000 to 27,600 daltons produced and secreted by cells in
response to viral infections and to synthetic or biological inducers.
Interferons exert their
cellular activities by binding to specific membrane receptors on the cell
surface. Once bound to the cell membrane, interferons initiate a complex
sequence of intracellular events. In vitro studies demonstrated that these
include the induction of certain enzymes, suppression of cell proliferation, immunomodulating
activities such as enhancement of the phagocytic activity of macrophages and
augmentation of the specific cytotoxicity of lymphocytes for target cells, and
inhibition of virus replication in virus-infected cells.
In a study using human hepatoblastoma
cell line HB 611, the in vitro antiviral activity of alpha interferon was
demonstrated by its inhibition of hepatitis B virus (HBV) replication.
The correlation between these in
vitro data and the clinical results is unknown. Any of these activities might
contribute to interferon's therapeutic effects.
The pharmacokinetics of INTRON®
A were studied in 12 healthy male volunteers following single doses of 5
million IU/m² administered intramuscularly, subcutaneously, and as a 30-minute
intravenous infusion in a crossover design.
The mean serum INTRON A
concentrations following intramuscular and subcutaneous injections were
comparable. The maximum serum concentrations obtained via these routes were
approximately 18 to 116 IU/mL and occurred 3 to 12 hours after administration.
The elimination half-life of INTRON A following both intramuscular and
subcutaneous injections was approximately 2 to 3 hours. Serum concentrations
were undetectable by 16 hours after the injections.
administration, serum INTRON A concentrations peaked (135- 273 IU/mL) by the
end of the 30-minute infusion, then declined at a slightly more rapid rate than
after intramuscular or subcutaneous drug administration, becoming undetectable
4 hours after the infusion. The elimination half-life was approximately 2 hours.
Urine INTRON A concentrations
following a single dose (5 million IU/m²) were not detectable after any of the
parenteral routes of administration. This result was expected since preliminary
studies with isolated and perfused rabbit kidneys have shown that the kidney
may be the main site of interferon catabolism.
There are no pharmacokinetic
data available for the intralesional route of administration.
Serum Neutralizing Antibodies
In INTRON A-treated patients
tested for antibody activity in clinical trials, serum anti-interferon
neutralizing antibodies were detected in 0% (0/90) of patients with hairy cell
leukemia, 0.8% (2/260) of patients treated intralesionally for condylomata
acuminata, and 4% (1/24) of patients with AIDS-Related Kaposi's Sarcoma. Serum
neutralizing antibodies have been detected in less than 3% of patients treated
with higher INTRON A doses in malignancies other than hairy cell leukemia or
AIDS-Related Kaposi's Sarcoma. The clinical significance of the appearance of
serum anti-interferon neutralizing activity in these indications is not known.
neutralizing antibodies were detected in 7% (12/168) of patients either during
treatment or after completing 12 to 48 weeks of treatment with 3 million IU TIW
of INTRON A therapy for chronic hepatitis C and in 13% (6/48) of patients who
received INTRON A therapy for chronic hepatitis B at 5 million IU QD for 4 months,
and in 3% (1/33) of patients treated at 10 million IU TIW. Serum
anti-interferon neutralizing antibodies were detected in 9% (5/53) of pediatric
patients who received INTRON A therapy for chronic hepatitis B at 6 million
IU/m² TIW. Among all chronic hepatitis B or C patients, pediatrics and adults
with detectable serum neutralizing antibodies, the titers detected were low
(22/24 with titers less than or equal to 1:40 and 2/24 with titers less than or
equal to 1:160). The appearance of serum anti-interferon neutralizing activity
did not appear to affect safety or efficacy.
Hairy Cell Leukemia
In clinical trials in patients
with hairy cell leukemia, there was depression of hematopoiesis during the
first 1 to 2 months of INTRON A treatment, resulting in reduced numbers of
circulating red and white blood cells, and platelets. Subsequently, both
splenectomized and nonsplenectomized patients achieved substantial and
sustained improvements in granulocytes, platelets, and hemoglobin levels in 75%
of treated patients and at least some improvement (minor responses) occurred in
90%. INTRON A treatment resulted in a decrease in bone marrow hypercellularity
and hairy cell infiltrates. The hairy cell index (HCI), which represents the
percent of bone marrow cellularity times the percent of hairy cell infiltrate,
was greater than or equal to 50% at the beginning of the study in 87% of
patients. The percentage of patients with such an HCI decreased to 25% after 6
months and to 14% after 1 year. These results indicate that even though
hematologic improvement had occurred earlier, prolonged INTRON A treatment may
be required to obtain maximal reduction in tumor cell infiltrates in the bone
The percentage of patients with
hairy cell leukemia who required red blood cell or platelet transfusions
decreased significantly during treatment and the percentage of patients with
confirmed and serious infections declined as granulocyte counts improved. Reversal
of splenomegaly and of clinically significant hypersplenism was demonstrated in
A study was conducted to assess
the effects of extended INTRON A treatment on duration of response for patients
who responded to initial therapy. In this study, 126 responding patients were
randomized to receive additional INTRON A treatment for 6 months or observation
for a comparable period, after 12 months of initial INTRON A therapy. During
this 6-month period, 3% (2/66) of INTRON A-treated patients relapsed compared
with 18% (11/60) who were not treated. This represents a significant difference
in time to relapse in favor of continued INTRON A treatment (P=0.006/0.01, Log
Rank/Wilcoxon). Since a small proportion of the total population had relapsed, median
time to relapse could not be estimated in either group. A similar pattern in relapses
was seen when all randomized treatment, including that beyond 6 months, and available
follow-up data were assessed. The 15% (10/66) relapses among INTRON A patients
occurred over a significantly longer period of time than the 40% (24/60) with observation
(P=0.0002/0.0001, Log Rank/Wilcoxon). Median time to relapse was estimated,
using the Kaplan-Meier method, to be 6.8 months in the observation group but
could not be estimated in the INTRON A group.
Subsequent follow-up with a
median time of approximately 40 months demonstrated an overall survival of
87.8%. In a comparable historical control group followed for 24 months, overall
median survival was approximately 40%.
The safety and efficacy of
INTRON A was evaluated as adjuvant to surgical treatment in patients with
melanoma who were free of disease (post surgery) but at high risk for systemic
recurrence. These included patients with lesions of Breslow thickness greater
than 4 mm, or patients with lesions of any Breslow thickness with primary or
recurrent nodal involvement. In a randomized, controlled trial in 280 patients,
143 patients received INTRON A therapy at 20 million IU/m² intravenously five
times per week for 4 weeks (induction phase) followed by 10 million IU/m²
subcutaneously three times per week for 48 weeks (maintenance phase). In the
clinical trial, the median daily INTRON A dose administered to patients was
19.1 million IU/m² during the induction phase and 9.1 million IU/m² during the
maintenance phase. INTRON A therapy was begun less than or equal to 56 days
after surgical resection. The remaining 137 patients were observed.
INTRON A therapy produced a
significant increase in relapse-free and overall survival. Median time to
relapse for the INTRON A-treated patients versus observation patients was 1.72
years versus 0.98 years (P<0.01, stratified Log Rank). The estimated 5-year
relapse-free survival rate, using the Kaplan-Meier method, was 37% for INTRON A-treated
patients versus 26% for observation patients. Median overall survival time for INTRON
A-treated patients versus observation patients was 3.82 years versus 2.78 years
(P=0.047, stratified Log Rank). The estimated 5-year overall survival rate,
using the Kaplan-Meier method, was 46% for INTRON A-treated patients versus 37%
for observation patients.
In a second study of 642
resected high-risk melanoma patients, subjects were randomized equally to one
of three groups: high-dose INTRON A therapy for 1 year (same schedule as above),
INTRON A therapy for 2 years (3 MU/d TIW SC), and observation. Consistent with
the earlier trial, high-dose INTRON A therapy demonstrated an improvement in
relapse-free survival (3-year estimated RFS 48% versus 41%; median RFS 2.4 versus
1.6 years, P=not significant). Relapse-free survival in the low-dose INTRON A
arm was similar to that seen in the observation arm. Neither high-dose nor low-dose INTRON A therapy
showed a benefit in overall survival as compared to observation in this study.
The safety and efficacy of
INTRON A in conjunction with CHVP, a combination chemotherapy regimen, was
evaluated as initial treatment in patients with clinically aggressive, large
tumor burden, Stage III/IV follicular Non-Hodgkin's Lymphoma. Large tumor
burden was defined by the presence of any one of the following: a nodal or extranodal
tumor mass with a diameter of greater than 7 cm; involvement of at least three
nodal sites (each with a diameter of greater than 3 cm); systemic symptoms;
splenomegaly; serous effusion, orbital or epidural involvement; ureteral
compression; or leukemia.
In a randomized, controlled
trial, 130 patients received CHVP therapy and 135 patients received CHVP
therapy plus INTRON A therapy at 5 million IU subcutaneously three times weekly
for the duration of 18 months. CHVP chemotherapy consisted of cyclophosphamide
600 mg/m², doxorubicin 25 mg/m², and teniposide (VM- 26) 60 mg/m², administered
intravenously on Day 1 and prednisone at a daily dose of 40 mg/m² given orally
on Days 1 to 5. Treatment consisted of six CHVP cycles administered monthly,
followed by an additional six cycles administered every 2 months for 1 year.
Patients in both treatment groups received a total of 12 CHVP cycles over 18
The group receiving the
combination of INTRON A therapy plus CHVP had a significantly longer progression-free
survival (2.9 years versus 1.5 years, P=0.0001, Log Rank test). After a median
follow-up of 6.1 years, the median survival for patients treated with CHVP
alone was 5.5 years while median survival for patients treated with CHVP plus
INTRON A therapy had not been reached (P=0.004, Log Rank test). In three
additional published, randomized, controlled studies of the addition of
interferon alpha to anthracycline-containing combination chemotherapy regimens,1-3
the addition of interferon alpha was associated with significantly prolonged
progression-free survival. Differences in overall survival were not
Condylomata acuminata (venereal
or genital warts) are associated with infections of the human papilloma virus
(HPV). The safety and efficacy of INTRON A in the treatment of condylomata
acuminata were evaluated in three controlled double-blind clinical trials. In
these studies, INTRON A doses of 1 million IU per lesion were administered
intralesionally three times a week (TIW), in less than or equal to 5 lesions
per patient for 3 weeks. The patients were observed for up to 16 weeks after
completion of the full treatment course.
INTRON A treatment of
condylomata was significantly more effective than placebo, as measured by
disappearance of lesions, decreases in lesion size, and by an overall change in
disease status. Of 192 INTRON A-treated patients and 206 placebotreated patients
who were evaluable for efficacy at the time of best response during the course
of the study, 42% of INTRON A patients versus 17% of placebo patients experienced
clearing of all treated lesions. Likewise, 24% of INTRON A patients versus 8%
of placebo patients experienced marked (75% to less than 100%) reduction in
lesion size, 18% versus 9% experienced moderate (50% to 75%) reduction in
lesion size, 10% versus 42% had a slight (less than 50%) reduction in lesion
size, 5% versus 24% had no change in lesion size, and 0% versus 1% experienced
In one of these studies, 43% (54/125)
of patients in whom multiple (less than or equal to 3) lesions were treated
experienced complete clearing of all treated lesions during the course of the
study. Of these patients, 81% remained cleared 16 weeks after treatment was
Patients who did not achieve
total clearing of all their treated lesions had these same lesions treated with
a second course of therapy. During this second course of treatment, 38% to 67%
of patients had clearing of all treated lesions. The overall percentage of patients
who had cleared all their treated lesions after two courses of treatment ranged
from 57% to 85%.
INTRON A-treated lesions showed
improvement within 2 to 4 weeks after the start of treatment in the above
study; maximal response to INTRON A therapy was noted 4 to 8 weeks after
initiation of treatment.
The response to INTRON A
therapy was better in patients who had condylomata for shorter durations than
in patients with lesions for a longer duration.
Another study involved 97
patients in whom three lesions were treated with either an intralesional
injection of 1.5 million IU of INTRON A per lesion followed by a topical application
of 25% podophyllin, or a topical application of 25% podophyllin alone. Treatment
was given once a week for 3 weeks. The combined treatment of INTRON A and
podophyllin was shown to be significantly more effective than podophyllin
alone, as determined by the number of patients whose lesions cleared. This
significant difference in response was evident after the second treatment (Week
3) and continued through 8 weeks post-treatment. At the time of the patient's
best response, 67% (33/49) of the INTRON A- and podophyllin-treated patients
had all three treated lesions clear while 42% (20/48) of the
podophyllin-treated patients had all three clear (P=0.003).
AIDS-Related Kaposi's Sarcoma
The safety and efficacy of
INTRON A in the treatment of Kaposi's Sarcoma (KS), a common manifestation of
the Acquired Immune Deficiency Syndrome (AIDS), were evaluated in clinical
trials in 144 patients.
In one study, INTRON A doses of
30 million IU/m² were administered subcutaneously three times per week (TIW) to
patients with AIDS-Related KS. Doses were adjusted for patient tolerance. The
average weekly dose delivered in the first 4 weeks was 150 million IU; at the
end of 12 weeks this averaged 110 million IU/week; and by 24 weeks averaged 75
Forty-four percent of
asymptomatic patients responded versus 7% of symptomatic patients. The median
time to response was approximately 2 months and 1 month, respectively, for
asymptomatic and symptomatic patients. The median duration of response was
approximately 3 months and 1 month, respectively, for the asymptomatic and
symptomatic patients. Baseline T4/T8 ratios were 0.46 for responders versus 0.33
In another study, INTRON A
doses of 35 million IU were administered subcutaneously, daily (QD), for 12
weeks. Maintenance treatment, with every other day dosing (QOD), was continued
for up to 1 year in patients achieving antitumor and antiviral responses. The
median time to response was 2 months and the median duration of response was 5
months in the asymptomatic patients.
In all studies, the likelihood
of response was greatest in patients with relatively intact immune systems as
assessed by baseline CD4 counts (interchangeable with T4 counts). Results at
doses of 30 million IU/m² TIW and 35 million IU/QD were subcutaneously similar
and are provided together in TABLE 1. This table demonstrates the relationship
of response to baseline CD4 count in both asymptomatic and symptomatic patients
in the 30 million IU/m² TIW and the 35 million IU/QD treatment groups.
In the 30 million IU study
group, 7% (5/72) of patients were complete responders and 22% (16/72) of the
patients were partial responders. The 35 million IU study had 13% (3/23
patients) complete responders and 17% (4/23) partial responders.
For patients who received 30
million IU TIW, the median survival time was longer in patients with CD4
greater than 200 (30.7 months) than in patients with CD4 less than or equal to
200 (8.9 months). Among responders, the median survival time was 22.6 months
versus 9.7 months in nonresponders.
Chronic Hepatitis C
The safety and efficacy of
INTRON A in the treatment of chronic hepatitis C was evaluated in 5 randomized
clinical studies in which an INTRON A dose of 3 million IU three times a week
(TIW) was assessed. The initial three studies were placebo-controlled trials
that evaluated a 6-month (24-week) course of therapy. In each of the three
studies, INTRON A therapy resulted in a reduction in serum alanine aminotransferase
(ALT) in a greater proportion of patients versus control patients at the end of
6 months of dosing. During the 6 months of follow-up, approximately 50% of the patients
who responded maintained their ALT response. A combined analysis comparing
pretreatment and post-treatment liver biopsies revealed histological improvement
in a statistically significantly greater proportion of INTRON A-treated patients
compared to controls.
Two additional studies have
investigated longer treatment durations (up to 24 months).5,6
Patients in the two studies to evaluate longer duration of treatment had hepatitis
with or without cirrhosis in the absence of decompensated liver disease. Complete
response to treatment was defined as normalization of the final two serum ALT
levels during the treatment period. A sustained response was defined as a complete
response at the end of the treatment period, with sustained normal ALT values
lasting at least 6 months following discontinuation of therapy.
In Study 1, all patients were
initially treated with INTRON A 3 million IU TIW subcutaneously for 24 weeks
(run-in-period). Patients who completed the initial 24-week treatment period
were then randomly assigned to receive no further treatment, or to receive 3
million IU TIW for an additional 48 weeks. In Study 2, patients who met the
entry criteria were randomly assigned to receive INTRON A 3 million IU TIW subcutaneously
for 24 weeks or to receive INTRON A 3 million IU TIW subcutaneously for 96
weeks. In both studies, patient follow-up was variable and some data collection
Results show that longer
durations of INTRON A therapy improved the sustained response rate (see TABLE
2). In patients with complete responses (CR) to INTRON A therapy after 6 months
of treatment (149/352 [42%]), responses were less often sustained if drug was
discontinued (21/70 [30%]) than if it was continued for 18 to 24 months (44/79
[56%]). Of all patients randomized, the sustained response rate in the patients
receiving 18 or 24 months of therapy was 22% and 26%, respectively, in the two
trials. In patients who did not have a CR by 6 months, additional therapy did
not result in significantly more responses, since almost all patients who
responded to therapy did so within the first 16 weeks of treatment.
A subset (less than 50%) of
patients from the combined extended dosing studies had liver biopsies performed
both before and after INTRON A treatment. Improvement in necroinflammatory
activity as assessed retrospectively by the Knodell (Study 1) and Scheuer
(Study 2) Histology Activity Indices was observed in both studies. A higher number
of patients (58%, 45/78) improved with extended therapy than with shorter (6 months)
therapy (38%, 34/89) in this subset.
Combination treatment with
INTRON A and REBETOL® (ribavirin USP) provided
a significant reduction in virologic load and improved histologic response in
adult patients with compensated liver disease who were treatment-naÃ¯ve or had
relapsed following therapy with alpha interferon alone; pediatric patients
previously untreated with alpha interferon experienced a sustained virologic
response. See REBETOL prescribing information for additional information.
Chronic Hepatitis B
The safety and efficacy of
INTRON A in the treatment of chronic hepatitis B were evaluated 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 versus 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,
evaluated 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 (less than or equal to 1.5 x 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 patients responding to 10 million IU TIW.
Improvement in liver histology was evaluated in Studies 1
and 3 by comparison of pretreatment and 6-month post-treatment 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
The safety and efficacy of INTRON A in the treatment of
chronic hepatitis B was evaluated 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
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] versus 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 less than 100
pg/mL were more likely to respond to INTRON A therapy than were patients with a
baseline HBV DNA greater than 100 pg/mL (35% versus 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% versus
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
|* Data for CD4, and asymptomatic and symptomatic
classification were not available for all patients.
TABLE 2: SUSTAINED ALT RESPONSE RATE VERSUS DURATION
OF THERAPY IN CHRONIC HEPATITIS C PATIENTS INTRON A 3 Million IU TIW
||Treatment Group* - Number of Patients (%)
|INTRON A 3 million IU
24 weeks of treatment
||INTRON A 3 million IU
72 or 96 weeks of treatment†
||Difference (Extended — 24
weeks) (95% CI)‡
||ALT response at the end of follow-up
||10% (-3, 24)
||13% (-4, 30)
||11.4% (2, 21)
||ALT response at the end of treatment
|| 32/67 (48%)
|| 35/80 (44%)
|* Intent-to-treat groups.
† Study 1: 72 weeks of treatment; Study 2: 96 weeks of treatment.
‡ Confidence intervals adjusted for multiple comparisons due to 3 treatment
arms in the study.
TABLE 3: VIROLOGIC RESPONSE* IN CHRONIC HEPATITIS B PATIENTS
|INTRON A 5 million IU QD
||INTRON A 10 million IU TIW
|* Loss of HBeAg and HBV DNA by 6 months post-therapy.
† Patients pretreated with prednisone not shown.
‡ INTRON A treatment group versus untreated control.
§ Untreated control patients evaluated after 24-week observation period. A
subgroup subsequently received INTRON A therapy. A direct comparison is not
TABLE 4: ALT RESPONSES* IN CHRONIC HEPATITIS B PATIENTS
||Treatment Group - Number of Patients (%)
|INTRON A 5 million IU QD
||INTRON A 10 million IU TIW
|* Reduction in serum ALT to normal by 6 months
† INTRON A treatment group versus untreated control.
‡ Untreated control patients evaluated after 24-week observation period. A
subgroup subsequently received INTRON A therapy. A direct comparison is not
1. Smalley R, et al. N Engl J Med. 1992;327:1336-1341.
2. Aviles A, et al. Leukemia and Lymphoma. 1996;20:495-499.
3. Unterhalt M, et al. Blood. 1996;88(10 Suppl 1):1744A.
5. Poynard T, et al. N Engl J Med. 1995;332(22)1457-1462.
6. Lin R, et al. J Hepatol. 1995;23:487-496.
7. Perrillo R, et al. N Engl J Med. 1990;323:295-301.
8. Perez V, et al. J Hepatol. 1990;11:S113-S117.
9. Knodell R, et al. Hepatology. 1981;1:431-435.
10. Perrillo R, et al. Ann Intern Med. 1991;115:113-115.