I saw this elsewhere as a news report - without the actual 'SVR Calculator'
data listed. This story has the data.

BeatHepC

Model to Predict Outcome of Pegasys plus Ribavirin Therapy

Reported by Jules Levin
39th EASL Conference
April 14-18, 2004
Berlin, Germany
ALL EASL REPORTS ARCHIVED ON NATAP WEBSITE: http://www.natap.org

??oCOMBINATION THERAPY WITH PEGINTERFERON ALFA-2A (40KD) (PEGASYS??)
PLUS RIBAVIRIN (COPEGUS) IN TREATMENT-NAIVE PATIENTS WITH CHRONIC HEPATITIS
C AND GENOTYPE 1 INFECTION: INDIVIDUAL ESTIMATED PROBABILITY OF SUSTAINED
VIROLOGICAL RESPONSE (SVR)???

O. Weiland (Karolinska Institutet, Stockholm, Sweden) presented the results
of this study at EASL (April 14-18, 2004, Berlin, Germany). Here is his
report.

Brief summary: This results from this study can be helpful in contributing
to making decisions about treatment for HCV, including when to begin HCV
therapy. These study results provide data showing response rates to
Pegasys/Copegus for patients with specific characteristics. The information
in this study discusses how to consider age, HCV viral load, BMI (body mass
index, i.e. body weight), ALT, and stage of liver disease in considering
when to begin therapy, the authors report how these factors affected patient
outcome and response rates.

Weiland said: Extensive analyses of date from pivotal studies has
demonstrated that SVR rates are heterogenous and are influenced by a range
of patient- and virus-specific characteristics. For this reason it is
possible to accurately predict the outcome of treatment for an individual
patient with chronic hepatitis C. The ability to more accurately predict the
outcome of treatment in an individual patient would be of practical value.
More accurate predictability data would allow physicians to better counsel
their patients on treatment decisions, and could be used to motivate
patients to start and to adhere to treatment with Pegasys/Copegus by
providing an accurate estimate of the probability of a cure. To this end we
constructed an "SVR Calculator'' for estimating the probability that an
individual patient will achieve an SVR after treatment with PEGASYS/COPEGUS.
The probability can be calculated at baseline, or after 12 weeks' treatment,
and can include assumptions about adherence.

The study objective was to present data from our logistic regression model
that demonstrates the ability to predict SVR in patients with HCV genotype 1
when treated with Pegasys/Copegus.

Data included were from patients treated with PEGASYS 180mcg/week and
COPEGUS 800 or 1000/1200mg/day in two phase III trials (Fried NEJM 2002;
Hadziyannis 2002).

The influence of pretreatment factors (gender, age, race, BMI/weight, viral
load, ALT quotient, histology, adherence) on SVR rates was examined by a
logistic regression model. Data falling outside the 5th-95th
percentiles were excluded; thus, data from 736 of 1037 genotype 1 patients
with these characteristics were used in the model: Caucasian men and women,
aged 18-65yrs, BMI 18-32 kg/m, ALT quotient, HCV RNA 0.1-24 million
copies/mL, histology.

SVR was defined as a single undetectable HCV RNA measurement (COBAS AMPLICOR
HCV Test v 2.0, limit of detection 65, no BMI or BMI >32, viral load 8.

Factors that significantly modified the probability of an SVR in patients
infected with genotype 1 included: age, viral load, ALT quotient, histology,
and BMI.

Note that these results are based on actual patient data from the two
studies and show the effects of two factors while ignoring other factors
included in the final model.

SVR RATES ACCORDING TO BASELINE AGE AND HCV RNA LEVEL

(data from 392 HCV genotype 1 patients treated for 48 weeks with Pegasys and
RBV 1000 or 1200 mg/day in Fried & Hadziyannis studies)

LOW HCV RNA 800,000 IU/ml

Age 18-34: 53.5% (24/43)
Age 35-50: 51.9% (81/156)
Age 51-65: 28% (14/50)

SVR RATES ACCORDING TO BASELINE AGE AND HCV RNA LEVEL (ADHERENT
PATIENTS ONLY)

(analysis limited to adherent patients??"datafrom 392 HCV genotype 1
patients treated for 48 weeks with Pegasys/Copegus 1000 or 1200 mg/day in
Fried & Hadziyannis studies)

LOW HCV RNA 800,000 IU/ml

Age 18-34: 59.5% (22/37)
Age 35-50: 65.0% (80/123)
Age 51-65: 36.4% (12/33)

SVR RATES ACCORDING TO BASELINE ALT QUOTIENT AND HCV RNA LEVEL

(data from 392 HCv genotype 1 patients treated for 48 weeks with
pegasys/Copegus 1000 or 1200 mg/day in Fried & Hadziyannis studies)

LOW HCV RNA 5.0 x ULN: 37.5% (3/8)

HIGH HCV RNA >800,000 IU/mL

ALT Quotient 5.0 x ULN: 68.2% (15/22)

SVR RATES ACCORDING TO BASELINE BMI AND HCV RNA LEVEL

(data from 392 HCV genotype 1 patients treated for 48 weeks with pegasys and
Copegus 1000 or 1200 mg/day in fried & Hadziyannis studies)

LOW HCV RNA 800,000 IU/ml

BMI ??? 25: 57.1% (64/112)
BMI ??? 25: 39.4% (54/137)

SVR RATES ACCORDING TO BASELINE AGE AND CIRRHOSIS STATE

(data from 392 HCV genotype 1 patients treated for 48 wks with
pegasys/Copegus 1000 or 1200 mg/day in Fried & Hadziyannis studies)

NO CIRRHOSIS

Age 18-34: 62.7% (47/75)
Age 35-50: 55.9% (105/188)
Age 51-65: 47.3% (26/55)

CIRRHOSIS/BRIDGING CIRRHOSIS

Age 18-34: 75% (3/4)
Age 35-50: 39% (16/41)
Age 51-65: 24.1% (7/29)

SVR RATES ACCORDING TO BASELINE ALT QUOTIENT AND CIRRHOSIS STATE

(data from 392 HCV genotype 1 patients treated for 48 wks with pegasys and
Copegus 1000 or 1200 mg/day in Fried & Hadziyannis studies)

NO CIRRHOSIS

ALT Quotient 5.0 x ULN: 75% (15/20)

CIRRHOSIS/BRIDGING CIRRHOSIS

ALT Quotient 5.0 x ULN: 30.0% (3/10)

SVR RATES ACCORDING TO BASELINE BMI AND CIRRHOSIS STATE

(data from 392 HCV genotype 1 patients treated for 48 wks with Pegasys and
Copegus 1000 or 1200 mg/day in Fried & Hadziyannis studies)

NO CIRRHOSIS

BMI ??? 25: 62.3% (96/154)
BMI ??? 25: 50% (82/164)

CIRRHOSIS/BRIDGING CIRRHOSIS

BMI ??? 25: 43.5% (10/23)
BMI ??? 25: 31.4% (16/51)

EFFECT OF VARIATION IN A SINGLE BASELINE

The effect of varying a single baseline characteristic on the probability of
achieving an SVR in a hypothetical ??~standard patient??T is presented
below, Note that individual estimated probabilities were generated with the
SVR calculator based on the final model.

PROBABILITY OF ACHIEVING A SUSTAINED VIROLOGIC RESPONSE

Standard patient: 52%
Viral load=60 x 103 IU/mL: 72%
Viral load=9000 x 103 IU/ml: 36%
Age=20 yrs: 70%
Age=60 yrs: 36%
BMI=20 kg/m2: 59%
BMI=30 kg/m2: 46%
ALT quotient=1.0: 45%
ALT quotient=4.0: 64%
Cirrhosis: 34%
Assuming adherence >80%: 62%

The characteristics of the ??~standard patient??T are as follows: HCV RNA
level 1200 x 103 IU/mL, age 43 yrs, BMI 26 kg/m2, ALT quotient 2.0, no
cirrhosis, and with no assumptions about adherence.

INDIVIDUAL ESTIMATED PROBABILITY OF AN SVR IN 8 HYPOTHETICAL PATIENTS WITH
GENOTYPE 1 FOR 48 WEEKS WITH PEGASYS PLUS COPEGUS 1000 or 1200 mg/day

The individual estimated probabilities of achieving an SVR is presented for
8 hypothetical patients below. Baseline characteristics used to calculate
the probabilities are presented.

PROBABILITY OF ACHIEVING SUSTAINED VIRAL RESPONSE

97% 85% 74% 52% 36% 19% 14% 7%
Cirrhosis: No No No No No No No Yes
ALT quotient: 7 2 2 2 2 2 1 1
Age: 20 20 43 43 43 60 60 60
BMI (kg/m2): 20 20 26 26 26 30 30 30
HCV RNA: 40 40 40 1200 9000 9000 9000 9000
(IU/ml x 103)

The authors CONCLUDED: the results of the SVR Calculator project demonstrate
that it is possible to refine the ability to estimate the probability that
an individual patient will achieve an SVR when treated with
Pegasy/Copegus. By varying the input parameters acci=ording to the
characteristics of an individual
patient the probability of achieving an SVR can be calculated. Important
baseline factors include HCV genotype, HCV RNA level, age, BMI, ALT
quotient, presence or absence of cirrhosis, and assumptions about adherence.
This tool can be used to make treatment decisions in clinical practice and
to motivate
patients to stay on therapy.