title: Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis.
abstract: BACKGROUND
  Adalimumab has been used in patients with moderately to severely active rheumatoid arthritis (RA) for over 10 years and has a well-established safety profile across multiple indications.
  
  
  OBJECTIVE
  To update adverse events (AEs) of special interest from global adalimumab clinical trials in patients with RA.
  
  
  METHODS
  This analysis includes 15 132 patients exposed to adalimumab in global RA clinical trials. AEs of interest included overall infections, laboratory abnormalities and AEs associated with influenza vaccination. Pregnancy outcome data were collected from the Adalimumab Pregnancy Registry.
  
  
  RESULTS
  Serious infections and tuberculosis occurred at a rate of 4.7 and 0.3 events/100 patient-years, respectively. Two patients experienced hepatitis B reactivation. No significant laboratory abnormalities were reported with adalimumab-plus-methotrexate compared with placebo-plus-methotrexate. Influenza-related AEs occurred in 5% of vaccinated patients compared with 14% of patients not vaccinated during the study. Relative risk of major birth defects and spontaneous abortions in adalimumab-exposed women were similar between that of unexposed women with RA and healthy women.
  
  
  CONCLUSIONS
  This analysis confirms and expands the known safety profile of adalimumab and reports no additional safety risk of laboratory abnormalities, hepatitis B reactivation and pregnancy outcomes, including spontaneous abortions and birth defects. The benefits of influenza vaccination are reinforced.
  
  
  BACKGROUND
  NCT00195663, NCT00195702, NCT00448383, NCT00049751, NCT00234845, NCT00650390, NCT00235859, NCT00647920, NCT00649545, NCT00647491, NCT00649922, NCT00538902, NCT00420927, NCT00870467, NCT00650156, NCT00647270, NCT01185288, NCT01185301.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Free University and Humboldt University of Berlin, Berlin, Germany.
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
authors.affiliation: Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Landewé
authors.affiliation: Division of Immunology and Rheumatology, Stanford University, Palo Alto, California, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Genovese
authors.affiliation: Immunology Clinical Development, AbbVie, North Chicago, Illinois, USA.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Friedman
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie, North Chicago, Illinois, USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Pfeifer
authors.affiliation: Data and Statistical Sciences, AbbVie, North Chicago, Illinois, USA.
authors.forename: Nupun A
authors.initials: NA
authors.lastname: Varothai
authors.affiliation: Immunology Clinical Development, AbbVie, North Chicago, Illinois, USA.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Lacerda
mesh_terms: D000022:Abortion, Spontaneous / Q000453:epidemiology*; D000068879:Adalimumab / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology; D002986:Clinical Trials as Topic; D000013:Congenital Abnormalities / Q000453:epidemiology*; D005260:Female; D006509:Hepatitis B / Q000453:epidemiology* / Q000209:etiology / Q000276:immunology; D006562:Herpes Zoster / Q000453:epidemiology / Q000209:etiology / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology; D015994:Incidence; D007252:Influenza Vaccines / Q000627:therapeutic use; D007251:Influenza, Human / Q000453:epidemiology* / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000453:epidemiology / Q000209:etiology / Q000276:immunology; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology* / Q000209:etiology / Q000276:immunology; D014775:Virus Activation / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; D007252:Influenza Vaccines; D000068879:Adalimumab
keywords: Anti-TNF; Rheumatoid Arthritis; Vaccination