Integrated safety analysis: short- and long-term safety profiles of etanercept in patients with psoriasis

J Am Acad Dermatol. 2012 Aug;67(2):245-56. doi: 10.1016/j.jaad.2011.07.040. Epub 2011 Oct 19.

Abstract

Background: Multiple trials demonstrate the tolerability and safety of etanercept. However, there are limited data on etanercept tolerability in large populations of patients with psoriasis or with extended therapy.

Objectives: We sought to determine whether there is an increased safety risk associated with higher etanercept doses or with extended exposure in patients with psoriasis.

Methods: Integrated adverse event (AE) data from etanercept psoriasis trials were used to evaluate short-term (up to 12 weeks from controlled studies) and long-term (up to 144 weeks from uncontrolled extension studies) safety of etanercept (25 mg once weekly to 50 mg twice weekly). Long-term data were stratified by treatment regimens. Rates of noninfectious and infectious AE and standardized incidence ratios for malignancies were determined.

Results: In short-term analyses, rates of noninfectious and infectious AE and serious noninfectious and infectious AE were comparable between placebo and etanercept groups. In both short- and long-term analyses, there were no dose-related increases in these events. Cumulative event rates for serious infections were not significantly different across dose groups and over time. The standardized incidence ratios for malignancies excluding nonmelanoma skin cancers did not achieve statistical significance. There was no increase in overall malignancies with etanercept therapy compared with the psoriasis population. Lymphoma (n = 2 patients), demyelination (n = 2), congestive heart failure (n = 7), and opportunistic infection (n = 1) were rare.

Limitations: Study limitations include the rarity of some events and the resultant broad 95% confidence intervals.

Conclusions: In this integrated analysis, etanercept was well tolerated, and there were no signs of dose-related or cumulative toxicity over time.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Adverse Drug Reaction Reporting Systems / statistics & numerical data*
  • Carcinoma, Basal Cell / epidemiology
  • Carcinoma, Squamous Cell / epidemiology
  • Controlled Clinical Trials as Topic / statistics & numerical data
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / adverse effects*
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Incidence
  • Male
  • Middle Aged
  • Opportunistic Infections / epidemiology
  • Psoriasis / drug therapy*
  • Psoriasis / epidemiology
  • Receptors, Tumor Necrosis Factor / administration & dosage
  • SEER Program / statistics & numerical data*
  • Severity of Illness Index
  • Skin Neoplasms / epidemiology
  • Time Factors

Substances

  • Immunoglobulin G
  • Immunosuppressive Agents
  • Receptors, Tumor Necrosis Factor
  • Etanercept