title: Safety profiles of adalimumab, etanercept and infliximab: a pharmacovigilance study using a measure of disproportionality in a database of spontaneously reported adverse events.
abstract: OBJECTIVE
  Despite being effective, the biologics approved for treating rheumatoid arthritis have been associated with serious adverse events. This study is aimed at comparing the safety profiles of adalimumab, etanercept and infliximab by analysing the disproportionalities of the associations between the different adverse events and the different biologics in the Portuguese spontaneous reporting database.
  
  
  METHODS
  Adverse events spontaneously reported to the Portuguese pharmacovigilance system (PPS) between 2009 and 2011 were included. Adverse events were classified according to MedDRA in the primary system organ class. The reporting odds ratio (ROR) and its 95% confidence intervals (CI) were calculated for each biologic regarding the various categories of adverse events. Microsoft Excel was used to perform all the calculations.
  
  
  CONCLUSIONS
  The PPS received 12167 adverse events reported for all drugs, of which 741 were reported for biologics: 157 for adalimumab, 132 for etanercept and 452 for infliximab. Compared with the all other drugs, adalimumab, etanercept and infliximab were all disproportionately associated with 'infections and infestations' (ROR: 6·65, 95% CI: 4·50-9·83; ROR: 2·74, 95% CI: 1·56-4·81; ROR: 2·95, CI 95%: 2·16-4·02, respectively) and with 'neoplasms benign, malignant and unspecified' (ROR: 7·23, 95% CI: 3·92-13·33; ROR: 6·26, 95% IC: 3·12-12·57; ROR: 3·94, 95% CI: 2·41-6·44, respectively), etanercept with 'general disorders and administration site conditions' (ROR: 2·08, 95% CI: 1·44-3·02) and infliximab with 'immune system disorders' (ROR: 5·17, 95% CI: 3·50-7·64), 'respiratory, thoracic and mediastinal disorders' (ROR: 1·80, 95% CI: 1·31-2·48) and 'investigations' (ROR: 1·82, 95% CI: 1·19-2·78). When interpreting the results one should take into consideration the number of patients exposed and should not only rely on the number of adverse events reported.
  
  
  CONCLUSIONS
  Although the disproportionalities found for adalimumab and etanercept may suggest strong associations with particular adverse events, caution is needed when drawing conclusions on the association between infliximab and the adverse events analysed. In the light of the present findings, these results deserve further evaluation.
authors.affiliation: CHAD - Centre for Health Technology Assessment and Drug Research, AIBILI - Association for Innovation and Biomedical Research on Light, Coimbra, Portugal; Central Portugal Regional Pharmacovigilance Unit, AIBILI - Association for Innovation and Biomedical Research on Light, Coimbra, Portugal; School of Pharmacy, University of Coimbra, Coimbra, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Mendes
authors.forename: C
authors.initials: C
authors.lastname: Alves
authors.forename: F
authors.initials: F
authors.lastname: Batel-Marques
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D060735:Pharmacovigilance; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept
keywords: adverse events; biologics; pharmacovigilance; reporting odds ratio; rheumatoid arthritis; spontaneous reporting