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Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis
  1. Gerd R Burmester1,
  2. Robert Landewé2,
  3. Mark C Genovese3,
  4. Alan W Friedman4,
  5. Nathan D Pfeifer5,
  6. Nupun A Varothai6,
  7. Ana P Lacerda4
  1. 1Department of Rheumatology and Clinical Immunology, Charité–University Medicine Berlin, Free University and Humboldt University of Berlin, Berlin, Germany
  2. 2Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
  3. 3Division of Immunology and Rheumatology, Stanford University, Palo Alto, California, USA
  4. 4Immunology Clinical Development, AbbVie, North Chicago, Illinois, USA
  5. 5Clinical Pharmacology and Pharmacometrics, AbbVie, North Chicago, Illinois, USA
  6. 6Data and Statistical Sciences, AbbVie, North Chicago, Illinois, USA
  1. Correspondence to Dr Gerd R Burmester, Department of Rheumatology and Clinical Immunology, Charité–University Medicine Berlin, Charitéplatz 1, Berlin 10017, Germany; gerd.burmester{at}


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.

  • Anti-TNF
  • Rheumatoid Arthritis
  • Vaccination

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  • Handling editor Tore K Kvien

  • Contributors GRB, RL, MCG, AWF and APL contributed to the design, review and interpretation of the data. NDP contributed to the review and interpretation of the data. NAV contributed to the analysis of the data.

  • Funding AbbVie sponsored the clinical trials.

  • Competing interests GRB has received research grants, consulting fees and speaker's fees from AbbVie, BMS, Merck, Pfizer, Roche and UCB. RL has received consulting fees from AbbVie, Amgen, BMS, Centocor, GSK, Merck, Novartis, Pfizer, Roche, Schering-Plough, UCB and Wyeth and is owner of Rheumatology Consultancy BV. MCG has received research grants and consulting fees from AbbVie. AWF, NDP and APL are employees of AbbVie and may hold stock and/or options. NV is a former employee of AbbVie and may hold stock and/or options.

  • Patient consent Obtained.

  • Ethics approval Appropriate Ethics Committee/Institutional review board approval was obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.