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Study 1 Citation: Stefan Zeuzem, MD, S. Victor Feinman, MD, Jens Rasenack, MD, E. Jenny Heathcote, MD, Ming-Yang Lai, MD, Edward Gane, MD, John O’Grady, MD, jurg Reichen, MD, Moises Diago, MD, Amy Lin, MS, Joseph Hoffman, MD, and Michael J. Brunda, PhD Peginterferon Alfa-2 in Patients with Chronic Hepatitis C New England Journal of Medicine, December 7, 2000 University of Massachusetts Medical Center, Worcester, MA; Massachusetts General Hospital, Boston, MA |
Click on the link at left to go to your desired page: Introduction Page 2 Page 3 Study 1 Study 2 Study 3 Conclusion Implication for Social Workers Post-Test
Abstract:
This randomized, prospective study compared the effect of a pegylated interferon regimen with an unmodified interferon regimen in the treatment of chronic hepatitis C. Group 1 (n=267) received 48 weeks of treatment with weekly subcutaneous injections of 180μg peginterferon alfa-2a while Group 2 (n=264) received 6 million units of unmodified interferon alfa-2a as subcutaneous injections three times weekly for the first twelve weeks followed by 3 million units of unmodified interferon for the remaining 36 weeks of the treatment arm of the study. Post-treatment observation was maintained for an additional 24 weeks to determine the sustained effect on viral load. Results suggested that the peginterferon regimen demonstrated a significantly better virologic response that was sustained through the post-treatment segment of the study. The adverse effects reported were similar to those reported in other interferon-based regimens and equivalent between the groups in this study. The authors concluded that the peginterferon regimen was more effective in achieving and sustaining a virologic response without any additional adverse effects compared to the unmodified interferon regimen.
interferon alfa, chronic hepatitis C, histologic response, peginterferon alfa
Discussion:
The researchers intended to show that peginterferon alfa was more effective at achieving and maintaining a sustained virologic response than unmodified interferon. Sustained response is seen in approximately 20% of patients on this regimen. Reasons given for this poor response rate are the short half-life of interferon alfa. Interferon combined with ribavirin has resulted in improved response rates, the authors noting 38 to 43% of patients showing a sustained virologic response. The researches note that peginterferon alfa has been developed to improve results by increasing the half-life and slowing the rate of clearance. This change also makes possible a once weekly dosing schedule, versus the three times weekly schedule required by unmodified interferon.
This randomized, prospective, multicenter trial divided the participants randomly among the group receiving peginterferon alfa once per week for 48 weeks (267 patients), or 6 million units unmodified interferon alfa three times weekly for 12 weeks, then 3 million units for a remaining 36 weeks (264 patients). All assessments were made at 48 weeks and again at 72 weeks.
Drop out rate was most significant in the unmodified interferon group with 103/264 lost during the treatment segment compared to 44/267 in the pegylated interferon group. An additional 7 patients in the unmodified interferon group and 17 patients in the pegylated interferon group did not complete the post-treatment observation segment of the study. The reasons given for study drop-out included lack of response to treatment (13 of the pegylated group versus 53 in the unmodified group), treatment refusal (5 pegylated and 13 unmodified), adverse events (19 pegylated and 27 unmodified), and others (7 pegylated and 10 unmodified).
Peginterferon alfa-2a was associated with a higher virologic response rate (defined as undetectable HCV RNA levels) than was unmodified interferon alfa. At week 48 of the study 69% of peginterferon patients achieved an undetectable viral load compared to 28% of the unmodified interferon group. Patients in the peginterferon group had a higher sustained virologic response rate (39% versus 19%), and a sustained normalization of serum alanine aminotransferase at week 72 in the peginterferon group that was not seen in the unmodified interferon group. Adverse events were similar between the two groups, and were associated with those commonly seen in unmodified interferon-alfa patients. Dose modification was required in 19% and 18% of the peginterferon and unmodified interferon groups respectively while 7% and 10% discontinued their participation because of adverse effects.
Results:
The researchers met their expectations with this study in finding that peginterferon alfa was more effective at maintaining a sustained virologic response than unmodified interferon alfa. Yet while the observed rate of response at end of treatment was higher in the peginterferon group, the rate of relapse at end of treatment was also higher in this same group between weeks 48 and 72.
In general the researchers concluded that peginterferon alfa was well tolerated and did not cause an increased amount, or any unexpected adverse events among this population of patients.
Summary of Study 1
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This randomized, prospective, and controlled study was conducted at multiple centers and has been considered one of the primary studies demonstrating the efficacy of peginterferon in chronic Hepatitis C. In this study, the use of peginterferon alfa versus unmodified interferon alfa showed a sustained virologic response. There was, however, a relapse in patients who did experience a response to peginterferon. Because peginterferon is given in a once weekly subcutaneous dose and adverse effects are well-established and not beyond those expected of interferon therapies, the homecare clinician can adequately assess the response to treatment. Monitoring should include monitoring of lab values (including liver function tests and blood counts) and assessing for signs and symptoms of psychiatric disturbances such as depression. |