Alopecia induced by tumour necrosis factor-alpha antagonists: description of 52 cases and disproportionality analysis in a nationwide pharmacovigilance database

Rheumatology (Oxford). 2014 Aug;53(8):1465-9. doi: 10.1093/rheumatology/keu145. Epub 2014 Mar 27.

Abstract

Objectives: The aim of this research was to describe the cases of TNF-α antagonist-related alopecia reported in the French Pharmacovigilance Database (FPVD) and to investigate the association between exposure to TNF-α antagonists and occurrence of alopecia.

Methods: All spontaneous reports of TNF-α antagonist-related alopecia recorded in the FPVD between January 2000 and April 2012 were colligated and described. We conducted disproportionality analyses (case/non-case method) to assess the link between the occurrence of alopecia and exposure to TNF-α antagonists. Cases were all reports of alopecia and non-cases were all other reports recorded during the study period. Exposure to TNF-α antagonists was sought in cases and in non-cases. Reporting odds ratios (RORs) were calculated to assess the association. Docetaxel was used as positive control and acetaminophen as negative control. We performed sensitivity analyses excluding cases of androgenic alopecia and those occurring in psoriatic patients.

Results: Among 282 590 spontaneous reports of adverse drug reactions (ADRs) collated in the FPVD, 1068 cases (alopecia reports) were identified. Of these cases, 52 (4.9%) occurred during exposure to TNF-α antagonists (18 involved infliximab, 17 adalimumab, 15 etanercept and 2 certolizumab). Exposure to TNF-α antagonists was more frequent among alopecia reports than among other ADR reports for all TNF-α antagonists pooled (ROR 3.0, 95% CI 2.3, 4.0) as well as for each antagonist separately, with similar values. Sensitivity analyses yielded similar results. The RORs were 29.9 (95% CI 25.3, 35.5) with docetaxel and 0.3 (95% CI 0.2, 0.4) with acetaminophen.

Conclusion: The present study confirms a strong link between TNF-α antagonist exposure (class effect) and the occurrence of alopecia.

Keywords: TNF-α antagonist; adalimumab; adverse drug reaction; alopecia; disproportionality analysis; etanercept; infliximab.

MeSH terms

  • Adalimumab
  • Adult
  • Adverse Drug Reaction Reporting Systems
  • Alopecia / chemically induced*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Certolizumab Pegol
  • Databases, Factual
  • Etanercept
  • Female
  • France
  • Humans
  • Immunoglobulin Fab Fragments / adverse effects
  • Immunoglobulin Fab Fragments / therapeutic use
  • Immunoglobulin G / adverse effects
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Male
  • Pharmacovigilance
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Polyethylene Glycols
  • Infliximab
  • Adalimumab
  • Etanercept
  • Certolizumab Pegol