title: Demyelinating disease in patients treated with TNF antagonists in rheumatology: data from BIOBADASER, a pharmacovigilance database, and a systematic review.
abstract: OBJECTIVE
  To estimate the rate of demyelinating diseases in patients with rheumatic diseases treated with tumor necrosis factor (TNF) antagonists and to describe the cases reported to 3 different pharmacovigilance sources.
  
  
  METHODS
  All confirmed cases of demyelinating disease, optic neuritis, and multiple sclerosis (MS) in patients with rheumatic diseases treated with TNF-antagonists were reviewed from 3 different sources: (1) the Spanish Registry of biological therapies in rheumatic diseases (BIOBADASER); (2) the Spanish Pharmacovigilance Database of Adverse Drug Reactions (FEDRA); and (3) a systematic review (PubMed, EMBASE, and the Cochrane Library). In BIOBADASER, the incidence rate per 1000 patients was estimated with a 95% confidence interval (95% CI).
  
  
  RESULTS
  In 21,425 patient-years in BIOBADASER, there were 9 patients with confirmed demyelinating disease, 4 with optic neuritis, and 1 with MS. In addition, 22 patients presented polyneuropathies, paresthesias, dysesthesias, facial palsy, or vocal cord paralysis without confirmed demyelination. The incidence rate of demyelinating disease in patients with rheumatic diseases exposed to TNF-antagonists in BIOBADASER was 0.65 per 1000 patient-years (95% CI: 0.39-1.1). The incidence of MS in BIOBADASER was 0.05 (95% CI: 0.01-0.33), while the incidence in the general Spanish population was 0.02 to 0.04 cases per 1000. Compared with BIOBADASER, cases in FEDRA (n = 19) and in the literature (n = 48) tend to be younger, have shorter exposure to TNF-antagonists, and recover after discontinuation of the drug.
  
  
  CONCLUSIONS
  It is not clear whether TNF antagonists increase the incidence of demyelinating diseases in patients with rheumatic diseases. Differences between cases depending on the pharmacovigilance source could be explained by selective reporting bias outside registries.
authors.affiliation: Rheumatology Department, Hospital Universitario de Móstoles, Móstoles, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Cruz Fernández-Espartero
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pérez-Zafrilla
authors.forename: Antonio
authors.initials: A
authors.lastname: Naranjo
authors.forename: Carmen
authors.initials: C
authors.lastname: Esteban
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ortiz
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gómez-Reino
authors.forename: Loreto
authors.initials: L
authors.lastname: Carmona
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016208:Databases, Factual; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D060735:Pharmacovigilance; D012216:Rheumatic Diseases / Q000188:drug therapy* / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha