Efficacy of etanercept in an integrated multistudy database of patients with psoriasis

https://doi.org/10.1016/j.jaad.2005.11.1088Get rights and content

Background

The tumor necrosis factor (TNF) inhibitor etanercept has been demonstrated to be safe and effective for treating chronic plaque psoriasis in 3 clinical trials.

Objectives

To refine efficacy results for etanercept on the basis of a larger population size through the integration of the 3 studies, and to determine if the efficacy profile across all 3 studies is consistent with efficacy profiles observed for individual trials.

Methods

In these integrated analyses, data for 1187 patients from 3 blinded treatment groups were pooled to compare efficacy at 12 weeks: etanercept 50 mg weekly (equivalent to 25 mg twice weekly) subcutaneously, etanercept 50 mg twice weekly subcutaneously, and placebo. The primary efficacy end point in all 3 studies was at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75). Other measurements included PASI 50, PASI 90, patient's and dermatologist's global assessments, and Dermatology Life Quality Index.

Results

In the integrated analyses, statistically significant, dose-dependent improvements in PASI 75 at 12 weeks were observed in patients treated with etanercept 50 mg weekly (33%) and 50 mg twice weekly (49%), compared with the placebo group (3%; P < .05). Significant improvements also were seen in all secondary end points (PASI 50 and PASI 90 responses, patient's and dermatologist's global assessments, and Dermatology Life Quality Index) at 12 weeks. Subgroup analyses of baseline patient characteristics demonstrated that there were no statistically significant treatment-by-covariate interactions.

Limitations

A limitation of these integrated analyses is the relatively short (12-week) time frame.

Conclusion

The efficacy profile of etanercept in patients with psoriasis was consistent across multiple studies as shown in the integrated analyses of the primary and secondary end points. Etanercept demonstrated rapid, dose-dependent improvements in disease severity and quality of life consistently over all studies.

Section snippets

Patient population

The institutional review boards of the participating medical centers approved the protocols. All patients gave written informed consent before initiation of the clinical trials. Patients included in the integrated analyses were eligible if they were 18 years of age or older; had active, stable plaque psoriasis involving at least 10% of body surface area (BSA); and were candidates for or had received previous phototherapy or systemic therapy for psoriasis. Patients in the phase 2 study required

Patient demographics and baseline characteristics

Across all studies, 773 patients received at least 1 dose of etanercept (50 mg weekly [n = 415] or 50 mg twice weekly [n = 358]), compared with 414 patients who received placebo. The severity of psoriasis in the patient population was consistent with moderate to severe psoriasis. Baseline patient demographics and characteristics were comparable between all 3 treatment groups (Table I). Patients were predominantly white men with severe psoriasis, 25% of whom had a prior diagnosis of psoriatic

Discussion

Psoriasis is a debilitating disease associated with major morbidity and negative impact on patients' lives. Etanercept therapy has been shown to significantly improve the physical and psychological burdens of the disease, as well as to improve the quality of life of affected individuals, in 3 placebo-controlled, double-blind clinical trials. In our integrated analyses, the results from these 3 studies were remarkably consistent with respect to efficacy within each study and across all studies

References (35)

  • G. Krueger et al.

    The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient-membership survey

    Arch Dermatol

    (2001)
  • S.R. Rapp et al.

    Social coping strategies associated with quality of life decrements among psoriasis patients

    Br J Dermatol

    (2001)
  • J. Choi et al.

    Quality of life issues in psoriasis

    J Am Acad Dermatol

    (2003)
  • J.G. Krueger

    The immunologic basis for the treatment of psoriasis with new biologic agents

    J Am Acad Dermatol

    (2002)
  • T.S. Kupper

    Immunologic targets in psoriasis

    N Engl J Med

    (2003)
  • C. Bonifati et al.

    Cytokines in psoriasis

    Int J Dermatol

    (1999)
  • D.M. Ashcroft et al.

    Therapeutic strategies for psoriasis

    J Clin Pharm Ther

    (2000)
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    Supported by Amgen Inc and Wyeth Research. Funded by Immunex Corporation, Seattle, Wash, a wholly owned subsidiary of Amgen Inc, Thousand Oaks, Calif, and by Wyeth. Data were collected by Amgen and stored in a central repository. Amgen provided statistical and editorial support.

    Conflicts of interest: Dr Gordon has received support and honoraria from the following companies: Abbott, Amgen, Biogen, Centocor, and Genentech. He received an honorarium for this work. Dr Korman has received grants from Amgen, has served as a clinical investigator for Amgen, and is on the Amgen speakers bureau. Dr Frankel serves on a speakers bureau for Amgen. Drs Wang, Jahreis, Zitnik, and Chang are employees of and have been granted stock options in Amgen, Inc.

    Reprints not available from the authors.

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