Is the risk of tumour necrosis factor inhibitor-induced lupus or lupus-like syndrome the same with monoclonal antibodies and soluble receptor? A case/non-case study in a nationwide pharmacovigilance database

Rheumatology (Oxford). 2014 Oct;53(10):1864-71. doi: 10.1093/rheumatology/keu214. Epub 2014 Jun 4.


Objective: Each TNF-α inhibitor (TNFi) can induce lupus or lupus-like syndrome. Nevertheless, the risk may differ between drugs because of different apoptosis induction properties. The aim of this study was to assess the putative association of each TNFi with lupus or lupus-like-syndrome.

Methods: All spontaneous reports of TNFi-related lupus recorded in the French pharmacovigilance database between January 2000 and December 2012 were described. We conducted disproportionality analyses (case/non-case method) to assess the link between TNFi and lupus, calculating reporting odds ratios (RORs). We used isoniazid as positive control and acetaminophen as negative control. We performed sensitivity analyses to test for event-related and drug-related competition biases.

Results: Among 309 671 spontaneous reports, 5213 involved TNFi. Among these, 39 were lupus or lupus-like syndromes: 25 involved infliximab, 9 adalimumab and 5 etanercept. The male:female sex ratio was 0.1 and the mean age was 44.9 years. Among the 39 cases, 28% fulfilled at least four ACR criteria for SLE. Median time to lupus onset was 11 months. Cutaneous and rheumatological involvement were the most frequent. Antinuclear autoantibodies were present in all patients, with anti-DNA specificity in 77.8%. Improvement was observed after TNFi withdrawal. There was a significant association between TNFi and lupus (ROR = 7.72, 95% CI 5.50, 10.83). The ROR was similar for infliximab (10.97, 95% CI 7.27, 16.56) and adalimumab (9.03, 95% CI 4.64, 17.58) and was 4.02 (95% CI 1.66, 9.75) for etanercept. Sensitivity analyses led to similar results.

Conclusion: Although CIs overlap, there is a clear trend towards a decreased risk with etanercept compared with monoclonal TNFis.

Keywords: TNF-α antagonists; disproportionality analysis; drug-induced lupus.

Publication types

  • Comparative Study

MeSH terms

  • Adalimumab
  • Adult
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Case-Control Studies
  • Databases, Pharmaceutical
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / adverse effects*
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Lupus Erythematosus, Systemic / chemically induced*
  • Male
  • Middle Aged
  • Pharmacovigilance
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Risk Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept