Gastroenterology

Gastroenterology

Volume 123, Issue 4, October 2002, Pages 1061-1069
Gastroenterology

Clinical–Liver, Pancreas, and Biliary Tract
Adherence to combination therapy enhances sustained response in genotype-1–infected patients with chronic hepatitis C,☆☆,

https://doi.org/10.1053/gast.2002.35950Get rights and content

Abstract

Background & Aims: Patient adherence to prescribed antiviral therapy in human immunodeficiency virus infection enhances response. We evaluated the impact of adherence to combination therapy with interferon or peginterferon plus ribavirin in chronic hepatitis C patients. Methods: We assessed the effect of dose reduction on sustained virologic response (SVR) from prior trials with interferon α-2b plus ribavirin (n = 1010) or peginterferon α-2b 1.5 μg/kg/week plus ribavirin (n = 511). The actual treatment administered was verified from drug dispensing/return records and patient diaries. Two groups were defined: (1) patients who received ≥80% of both their total interferon and ribavirin doses for ≥80% of the expected duration of therapy and (2) patients who received reduced doses (<80% of one or both drugs for ≥80% of the expected duration of therapy). A statistical model provided comparative estimates of the response rates in compliant patients. Results: Most patients were at least 80% compliant with interferon α-2b/ribavirin or peginterferon α-2b/ribavirin therapy and had SVR rates of 52% and 63%, respectively, for the 2 regimens. This was most apparent for HCV-1–infected patients. The impacts of adherence on efficacy from subgroup analysis and the statistical modeling approach were similar. Conclusions: HCV-1–infected patients who can be maintained on >80% of their interferon or peginterferon α-2b and ribavirin dosage for the duration of treatment in the setting of a clinical trial exhibit enhanced sustained response rates. Our results suggest that adherence will enhance the likelihood of achieving an initial virologic response. Adherence beyond 12–24 weeks will be advantageous only for those patients who have achieved such an early virologic response.

GASTROENTEROLOGY 2002;123:1061-1069

Section snippets

Patient selection

Data for patients from 3 previously published clinical trials of interferon α-2b or peginterferon α-2b and ribavirin combination therapy were evaluated retrospectively to determine the effect of dose reduction on sustained response (Figure 1).3, 4, 7

. Schematic diagram of the 4 studies performed with regimens of interferon α-2b or peginterferon α-2b plus ribavirin,3, 4, 7 and peginterferon α-2b or interferon α-2b alone.10 Asterisks indicate the groups of patients where adherence was evaluated

Results

Of the 1010 patients evaluated who received interferon α-2b plus ribavirin, 218 were excluded from further analysis because the duration of therapy was <80% of the assigned treatment regimen. Most of the remaining patients who were treated for longer than 80% of the planned duration, 631 of 792 (80%), also received >80% of both their interferon α-2b and ribavirin doses. Similarly, for the 511 patients receiving peginterferon α-2b 1.5 μg · kg−1 · wk−1 plus ribavirin, 88 were excluded from the

Discussion

This retrospective analysis indicates that adherence to therapy with interferon α-2b or peginterferon α-2b plus ribavirin for patients with chronic hepatitis C is important and enhances sustained response rates. This observation was apparent only for HCV-1–infected patients, those most difficult to treat. Moreover, the fact that results obtained with 2 different approaches—subgroup analysis of observed data and modeling—produced similar results strengthens the premise that adherent patients are

Acknowledgements

The authors thank Elvia Nunez of the Scripps Clinic for preparing this manuscript. The authors also thank all participating investigators in these randomized controlled trials. Their individual names and sites appear in the appendices attached to each of the separate publications.

References (22)

  • RG Knodell et al.

    Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis

    Hepatology

    (1981)
  • Cited by (0)

    Address requests for reprints to: John G. McHutchison, M.D., Duke Clinical Research Institute, Duke University Medical Center, P.O. Box 17969, Durham, North Carolina 27715. e-mail: [email protected]; fax: (919) 668-7164.

    ☆☆

    Supported in part by research grants from the Schering-Plough Research Institute, Kenilworth, New Jersey, and clinical research center grants from Massachusetts General Hospital (MO1-RR01066), the Scripps Clinic (MO1-RR00833), and Los Angeles County–University of Southern California Medical Center (M01-RR00043).

    Dr. McHutchison is an advisor and consultant and has received research support from Schering-Plough. Dr. Manns is an ad hoc consultant to and a recipient of research grants from Schering-Plough. Dr. Poynard works on the Principal Investigator and Speaker Bureau for Schering-Plough. Dr. Lindsay is a speaker for Schering-Plough and has received research support from Schering-Plough, Glaxo Wellcome, Hoffman-Rodel, Scripps Liver Research Consortium, and Triangle Pharmaceuticals. Dr. Dienstag has received research support and has served on an adjudication board for Schering-Plough. Drs. Mak and Albrecht are employees of Schering-Plough and own stock in the corporation.

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