[NATAP] Pegasys/RBV Retreatment for IFN/RBV Failures

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Pegasys/RBV Retreatment for IFN/RBV Failures

Reported by Jules Levin

Over the weekend I sent a report out to you with the preliminary results from

the EPIC Study, which examines re-treatment with PegIntron plus RBV in patients

previously treated with interferon+ribavirin. Poynard reported a preliminary SVR

of 21%. Also at EASL April 2005, a poster reported results from an Canadian

open-label Pegasys Expanded Access Program. This poster reports a 23% SVR rate

for patients who previously failed interferon+ribavirin and only 800mg per day

of ribavirin was used rather than the recommended 1000 or 1200mg. However, you

are not supposed to compare results from different studies, particularly because

often the baseline characteristics of patients very between studies & this

affects the outcomes.

Peginterferon alfa-2a (40D) Pegasys) plus ribavirin (Copegus) in chronic

hepatitis C patients wjo failed previous interferon based therapy: results of a

multicenter open-label expanded access programme in Canada

M Sherman & colleagues reported these study results & information at the 40th

EASl in Paris in a poster.

INTRODUCTION

In randomized, multicenter phase III studies, overall SVR rates of up to 63%

have been achieved in patients treated with Pegasys plus Copegus (ribavirin):

46-52% in HCV genotype 1 & 76-84% in HCV genotype 2 or 3 patients.

The management of patients who have relapsed or failed to respond to previous

interferon-based therapy is an important, but as yet unresolved, issue in the

management of chronic hepatitis.

This study evaluates the efficacy & tolerability of Pegasys plus ribavirin in

relapsers & nonresponders enrolled in the Canadiam multicenter expanded access

program.

STUDY DESIGN

The study patients were those who relapsed or who failed to respond to previous

conventional interferon. Patients were assigned at their physician's discretion

to receive combinatiob therapy with Pegasys+RBV 800mg per day for 24 or 48

weeks.. SVR was defined as undetectable HCV RNA (<50 IU/mL by Cobas Amplicor HCV

Test, v2.0) at the end of a 24-week untreated follow-up period ( week 48 in the

24-week treatment group & week 72 in the 48-week treatment group). A total of

361 patients were enrolled. 355 patients were assigned to combination therapy &

6 patients were assigned Pegasys monotherapy. Analyses were conducted using the

intent-to-treat (ITT) population.

RESULTS

Patients assigned to combination therapy had received previous interferon-based

therapy (119 relapsers & 236 non-responders). Of these 355 patients, 253

individuals (71%) had received previous IFN plus RBV (67% of relapsers & 73% of

non-responders).

Baseline characteristics were generally similar between relapsers &

non-responders, although a higher proportion of non-responders than relapsers

had HCV genotype 1 (84% vs 65%).

GENOTYPE 1: 65% relapsers; 84% nonresponders

70% males

age: 47 yrs

88% Caucasian

weight: 80 kg

BMI: 27 kg/m2

HCV RNA: 32-37% >850,000 IU/mL; 23-27% 500,000 to 850,000 IU/mL; 40% <500,000

IU/ml

No cirrhosis: 50%

Transition to cirrhosis (F3): 21-23%

Cirrhosis (F4): 23-29%

75% of the nonresponders had previous therapy with IFN/RBV & 67% of relapsers

hadIFN/RBV therapy.

RESULTS

Overall, 48/119 (40%) relapsers & 54/236 (23%) non-responders achieved an SVR

following treatment with pegasys plus ribavirin.

NON-RESPONDERS

All genotypes: 23%

Genotype 1: 20%

Genotype 2/3: 35%

RELAPSERS

All genotypes: 40%

Genotype 1: 35%

Genotype 2/3: 51%

SVR ACCORDING to PREVIOUS THERAPY

Previous Therapy HCV geno SVR

Relapsers Nonrespond

IFN monotherapy 1 10/24 (42%) 10/49 (20%)

2/3 7/14 (50%) 4/11 (36%)

IFN+RBV 1 17/54 (31%) 29/149 (19%)

2/3 12/23 (52%) 7/11 (35%)

SAFETY

The overall incidence of serious adverse events was similar in non-responders &

relapsers. A total of 12 adverse events were reported in 11 of the 236

non-responders (5%) & a total of 14 adverse events were reported in 9 of 119

relapsers (8%). Overall, 10 events occurring 9 patients were judged to be

related to study treatment by the investigators.

Similar proportions of relapsers & responders receiving 48 wks of therapy

requiring peginterferon required Pegasys dose modifications for neutropenis (23%

vs 19%), or thrombocytopenis (7% vs 6%) & RBV dose mod modifications for anemia

(10% vs 8%).

ADVERSE EVENTS & LAB ABNORMALITIES REQUIRING DOSE MODIFICATION (which could be

temporary or permanent)

24 wks 48 wks

Relapsers n=19 n=100

Any AE 5 49

SAE 0 9

Lab abnormality requiring Pegasys dose mod

Neutropenia 2 23

Thrombocytopenia 0 7

Anemia requiring RBV dose mod

1 10

Non-Responders n=13 n=223

Any AE 3 105

SAE 1 10

Lab abnormality requiring Pegasys dose mod

Neutropenia 2 43 (19%)

Thrombocytopenia 1 13 (6%)

Anemia requiring RBV dose mod

0 17 (8%)

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[Guest guest]

NATAP - http://www.natap.org

Pegasys/RBV Retreatment for IFN/RBV Failures

Reported by Jules Levin

Over the weekend I sent a report out to you with the preliminary results from

the EPIC Study, which examines re-treatment with PegIntron plus RBV in patients

previously treated with interferon+ribavirin. Poynard reported a preliminary SVR

of 21%. Also at EASL April 2005, a poster reported results from an Canadian

open-label Pegasys Expanded Access Program. This poster reports a 23% SVR rate

for patients who previously failed interferon+ribavirin and only 800mg per day

of ribavirin was used rather than the recommended 1000 or 1200mg. However, you

are not supposed to compare results from different studies, particularly because

often the baseline characteristics of patients very between studies & this

affects the outcomes.

Peginterferon alfa-2a (40D) Pegasys) plus ribavirin (Copegus) in chronic

hepatitis C patients wjo failed previous interferon based therapy: results of a

multicenter open-label expanded access programme in Canada

M Sherman & colleagues reported these study results & information at the 40th

EASl in Paris in a poster.

INTRODUCTION

In randomized, multicenter phase III studies, overall SVR rates of up to 63%

have been achieved in patients treated with Pegasys plus Copegus (ribavirin):

46-52% in HCV genotype 1 & 76-84% in HCV genotype 2 or 3 patients.

The management of patients who have relapsed or failed to respond to previous

interferon-based therapy is an important, but as yet unresolved, issue in the

management of chronic hepatitis.

This study evaluates the efficacy & tolerability of Pegasys plus ribavirin in

relapsers & nonresponders enrolled in the Canadiam multicenter expanded access

program.

STUDY DESIGN

The study patients were those who relapsed or who failed to respond to previous

conventional interferon. Patients were assigned at their physician's discretion

to receive combinatiob therapy with Pegasys+RBV 800mg per day for 24 or 48

weeks.. SVR was defined as undetectable HCV RNA (<50 IU/mL by Cobas Amplicor HCV

Test, v2.0) at the end of a 24-week untreated follow-up period ( week 48 in the

24-week treatment group & week 72 in the 48-week treatment group). A total of

361 patients were enrolled. 355 patients were assigned to combination therapy &

6 patients were assigned Pegasys monotherapy. Analyses were conducted using the

intent-to-treat (ITT) population.

RESULTS

Patients assigned to combination therapy had received previous interferon-based

therapy (119 relapsers & 236 non-responders). Of these 355 patients, 253

individuals (71%) had received previous IFN plus RBV (67% of relapsers & 73% of

non-responders).

Baseline characteristics were generally similar between relapsers &

non-responders, although a higher proportion of non-responders than relapsers

had HCV genotype 1 (84% vs 65%).

GENOTYPE 1: 65% relapsers; 84% nonresponders

70% males

age: 47 yrs

88% Caucasian

weight: 80 kg

BMI: 27 kg/m2

HCV RNA: 32-37% >850,000 IU/mL; 23-27% 500,000 to 850,000 IU/mL; 40% <500,000

IU/ml

No cirrhosis: 50%

Transition to cirrhosis (F3): 21-23%

Cirrhosis (F4): 23-29%

75% of the nonresponders had previous therapy with IFN/RBV & 67% of relapsers

hadIFN/RBV therapy.

RESULTS

Overall, 48/119 (40%) relapsers & 54/236 (23%) non-responders achieved an SVR

following treatment with pegasys plus ribavirin.

NON-RESPONDERS

All genotypes: 23%

Genotype 1: 20%

Genotype 2/3: 35%

RELAPSERS

All genotypes: 40%

Genotype 1: 35%

Genotype 2/3: 51%

SVR ACCORDING to PREVIOUS THERAPY

Previous Therapy HCV geno SVR

Relapsers Nonrespond

IFN monotherapy 1 10/24 (42%) 10/49 (20%)

2/3 7/14 (50%) 4/11 (36%)

IFN+RBV 1 17/54 (31%) 29/149 (19%)

2/3 12/23 (52%) 7/11 (35%)

SAFETY

The overall incidence of serious adverse events was similar in non-responders &

relapsers. A total of 12 adverse events were reported in 11 of the 236

non-responders (5%) & a total of 14 adverse events were reported in 9 of 119

relapsers (8%). Overall, 10 events occurring 9 patients were judged to be

related to study treatment by the investigators.

Similar proportions of relapsers & responders receiving 48 wks of therapy

requiring peginterferon required Pegasys dose modifications for neutropenis (23%

vs 19%), or thrombocytopenis (7% vs 6%) & RBV dose mod modifications for anemia

(10% vs 8%).

ADVERSE EVENTS & LAB ABNORMALITIES REQUIRING DOSE MODIFICATION (which could be

temporary or permanent)

24 wks 48 wks

Relapsers n=19 n=100

Any AE 5 49

SAE 0 9

Lab abnormality requiring Pegasys dose mod

Neutropenia 2 23

Thrombocytopenia 0 7

Anemia requiring RBV dose mod

1 10

Non-Responders n=13 n=223

Any AE 3 105

SAE 1 10

Lab abnormality requiring Pegasys dose mod

Neutropenia 2 43 (19%)

Thrombocytopenia 1 13 (6%)

Anemia requiring RBV dose mod

0 17 (8%)

_______________________________________________

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hcv@...

http://natap.org/mailman/listinfo/hcv_natap.org

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_______________________________________________

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hcv@...

http://natap.org/mailman/listinfo/hcv_natap.org