Clinical trial safety and mortality analyses in patients receiving etanercept across approved indications

J Drugs Dermatol. 2011 Mar;10(3):289-300.


Objectives: Assessment of associations between etanercept treatment and rare adverse events has been limited by the size of clinical trial populations. The authors examined the collective safety of etanercept in clinical trials across approved indications.

Patients and methods: Forty-nine U.S. and non-U.S. trials of etanercept, involving up to 13,977 patients for approved indications, with final trial reports as of May 2006, were selected from the Amgen Inc. clinical trials database. Exposure-adjusted rates of serious infections, opportunistic infections, malignancies, and deaths were reported by trial, indication, and dosage.

Results: Rates of serious infections were generally similar between etanercept and controls. Overall rates of opportunistic infections and tuberculosis were low. The standardized incidence ratio (SIR) (95% CI) for malignancy was 1.00 (0.83-1.19) for all etanercept patients across all indications. The SIR for lymphoma for patients with rheumatoid arthritis was 3.45 (1.83-5.89); all other indications reported SIRs similar to those observed in the general population. The SIRs for cutaneous squamous cell carcinoma in patients with psoriasis relative to the general population with high or low sun exposure were 2.09 (1.27-3.22) and 4.96 (3.03-7.66), respectively. SIRs were less than 1.0 for all other indications regardless of sun exposure. Rates of melanoma and basal cell carcinoma were not significantly different from those in the general population. There was no increase in mortality associated with etanercept use relative to control populations.

Conclusion: These data support the overall tolerability of etanercept across approved indications.

MeSH terms

  • Arthritis, Juvenile / drug therapy
  • Arthritis, Psoriatic / drug therapy
  • Arthritis, Rheumatoid / drug therapy
  • Clinical Trials as Topic
  • Databases, Factual
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Etanercept
  • Humans
  • Immunoglobulin G / adverse effects*
  • Immunoglobulin G / therapeutic use
  • Immunologic Factors / adverse effects*
  • Immunologic Factors / therapeutic use
  • Infections / epidemiology*
  • Neoplasms / epidemiology
  • Neoplasms / mortality
  • Opportunistic Infections / epidemiology
  • Psoriasis / drug therapy
  • Receptors, Tumor Necrosis Factor / antagonists & inhibitors*
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Spondylitis, Ankylosing / drug therapy
  • Time Factors
  • Treatment Outcome


  • Immunoglobulin G
  • Immunologic Factors
  • Receptors, Tumor Necrosis Factor
  • Etanercept