• 18
    Jun
  • Peginterferon alfa-2a: EFFICACY

The safety and efficacy of Pegasys® were assessed in three randomized, open-labeled, active-controlled clinical studies. All of the patients were adults, had compensated liver disease and detectable HCV, and had not been treated with interferon previously. All patients received therapy by subcutaneous (SQ) injection for 48 weeks and were monitored for an additional 24 weeks to assess the durability of their responses.

In studies 1 and 2, approximately 20% of subjects had cirrhosis or experienced a transition to cirrhosis. Study 3 was designed to enroll only patients with a histological diagnosis of cirrhosis.
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  • In study 1 (n = 630), patients received either interferon alfa-2a (Roferon®-A, Roche) 3 million International Units (IU) three times a week, Pegasys® 135 mcg once each week, or Pegasys® 180 mcg once each week.
  • In study 2 (n = 526), patients received either Roferon®-A 6 million IU three times a week for 12 weeks, followed by 3 million IU three times a week for 36 weeks, or Pegasys® 180 mcg once each week.
  • In study 3 (n = 269), patients received Roferon®-A 3 million IU three times a week, Pegasys® 90 mcg once each week, or Pegasys® 80 mcg once each week.

In all three studies, patients who received Pegasys® 180 mcg responded significantly better than those receiving Roferon®-A (Tables 1 to 3). In study 1, responses to Pegasys® 135 mcg did not differ from the responses to 180 mcg. In study 3, response rates with Pegasys® 90 mcg were intermediate between Pegasys® 180 mcg and Roferon®-A. In addition, some studies indicated that it could be determined at week 12 of treatment whether a subject was unlikely to attain a sustained virological response with Pegasys®. This information would be helpful in deterring patients from continuing a therapy to which they would most likely be unresponsive.

Table 1    Sustained Responses of Patients with Hepatitis C Virus Infection to Three Interferons at Week 72

Study 1

Interferon alfa-2a (Roferon®-A, Roche) 3 million IU (n = 207)

Peginterferon alfa-2a (Pegasys®, Roche) 135 mcg (n = 215) Peginterferon alfa-2a (Pegasys®, Roche) 180 mcg(n = 208)
Combined virological response and biological sustained responder (week 72) 11%

11%

24%

Sustained virological response* 26%

24%

26%

* COBAS AMPLICOR® HCV Test, version 2.0, is a registered trademark of Roche Molecular Systems, Inc.Data from Prescribing Information for peginterferon alfa-2a (Pegasys®). Nutley, NJ: Hoffman-La Roche Inc., October 2002.7

Manns and colleagues compared Pegasys® plus ribavirin with interferon alfa-2b plus ribavirin (Scher­ing) and with Pegasys® monotherapy over 24 weeks. In this trial, Pegasys® in combination with achieved a 56% sustained response versus a 45% response in the former standard of care (RebetronTM). Patients taking the combination of Pegasys® and ribavirin also experienced lower rates of flu-like symptoms and depression than did patients taking Rebetron canadian.

Table 2 Sustained Responses of Patients with Hepatitis C Virus Infection to Two Interferons at Week 72

Study 2

Interferon alfa-2a (Roferon®-A, Roche) 6 million IU (12 wk) + 3 million IU (24 wk) (n = 261)

Peginterferon alfa-2a (Pegasys®, Roche) 180 mcg (36 wk) (n = 265)

Combined virological response and                                         17% biological sustained responder (week 72) 35%
Sustained virological response*                                              19% 38%
* COBAS AMPLICOR® HCV Test, version 2.0, is a registered trademark of Roche Molecular Systems, Inc.Data from Prescribing Information for peginterferon alfa-2a (Pegasys®). Nutley, NJ: Hoffman-La Roche Inc., October 2002.7

Hassanein and colleagues compared the quality of life in patients with chronic hepatitis C with the combination therapy of Pegasys® plus ribavirin canadian with that in patients taking RebetronTM. During a 72-week study, patients were randomly assigned to receive Pegasys® plus riba-virin, RebetronTM, or Pegasys plus a placebo. The researchers assessed quality of life and the impact of fatigue using the Short-Form Health Survey (SF-36®) and the Fatigue Severity Scale (FSS). After 48 weeks of treatment, patients receiving Pegasys® plus ribavirin reported better quality of life and less fatigue than those taking RebetronTM on all domains of the SF-36® and the FSS, with statistically significant differences in vitality, body pain, social functioning, and burden of fatigue. Similarly, patients receiving Pegasys® monotherapy also reported a better quality of life than those given RebetronTM according to the same testing instruments. These findings have clinical importance because better quality of life during treatment has been shown to reduce the risk of premature discontinuation of therapy.

Table 3 Sustained Responses of Patients with Hepatis C Virus Infection and a Definitive Diagnosis of Cirrhosis to Three Interferons at Week 72

Study 3
Interferon alfa-2a(Roferon®-A, Roche)

3 million IU

(n = 86)

Peginterferon alfa-2a (Pegasys®, Roche) 90 mcg(n = 96) Peginterferon alfa-2a (Pegasys®, Roche) 180 mcg (n = 87)
Combined virological response and biological sustained responder (week 72)

7%

23%

Sustained virological response*

8%

15%

30%

* COBAS AMPLICOR® HCV Test, version 2.0, is a registered trademark of Roche Molecular Systems, Inc.Data from Prescribing Information for peginterferon alfa-2a (Pegasys®). Nutley, NJ: Hoffman-La Roche Inc., October 2002;7 and Fried M. Clin Liver Dis2001;5(4):1009-1023.8

ADVERSE REACTIONS

Peginterferon alfa-2a therapy can cause a wide variety of serious adverse drug reactions (Table 4). Nearly all patients in the clinical trials experienced one or more adverse events. The most commonly reported effects were gastro­intestinal symptoms (e.g., nausea, diarrhea, and abdominal pain), flulike symptoms (e.g., fatigue, pyrexia, rigors, myalgia, and headache), and psychiatric reactions (e.g., depression, irritability, and anxiety).

Table 4 Adverse Reactions Occurring in 5% or More of Patients with Hepatitis C Virus Infection in Clinical Trials of Peginterferon alfa-2a

Interferon alfa-2a Body System/        (Pegasys®, Roche) Adverse Event            (180 mcg)
Gastrointestinal
Nausea 23%
Diarrhea 16%
Abdominal pain 15%
General
Fatigue 50%
Pyrexia 36%
Rigors 32%
Tissue and Bone
Myalgia 37%
Arthralgia 28%
Back pain 9%
Neurological
Headache 54%
Insomnia 19%
Dizziness 16%
Psychiatric
Depression 18%
Irritability 13%
Anxiety 6%
Data from Prescribing Information for peginterferon alfa-2a (Pegasys®). Nutley, NJ: Hoffman-La Roche Inc., October 2002.7
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