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Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn's disease
  1. Gerd R Burmester1,
  2. Remo Panaccione2,
  3. Kenneth B Gordon3,
  4. Melissa J McIlraith4,
  5. Ana P M Lacerda5
  1. 1Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany
  2. 2Department of Medicine, University of Calgary, Calgary, Canada
  3. 3Department of Dermatology, Northwestern University, Chicago, Illinois, USA
  4. 4Department of Rheumatology Medical Affairs, Abbott Laboratories, Rungis, France
  5. 5Immunology Medical Affairs, Abbott Laboratories, Sao Paulo, Brazil
  1. Correspondence to Professor G R Burmester, Department of Rheumatology and Clinical Immunology, Charité – University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany; gerd.burmester{at}


Background As long-term treatment with antitumour necrosis factor (TNF) drugs becomes accepted practice, the risk assessment requires an understanding of anti-TNF long-term safety. Registry safety data in rheumatoid arthritis (RA) are available, but these patients may not be monitored as closely as patients in a clinical trial. Cross-indication safety reviews of available anti-TNF agents are limited.

Objective To analyse the long-term safety of adalimumab treatment.

Methods This analysis included 23 458 patients exposed to adalimumab in 71 global clinical trials in RA, juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis, psoriasis (Ps) and Crohn's disease (CD). Events per 100 patient-years were calculated using events reported after the first dose through 70 days after the last dose. Standardised incidence rates for malignancies were calculated using a National Cancer Institute database. Standardised death rates were calculated using WHO data.

Results The most frequently reported serious adverse events across indications were infections with greatest incidence in RA and CD trials. Overall malignancy rates for adalimumab-treated patients were as expected for the general population; the incidence of lymphoma was increased in patients with RA, but within the range expected in RA without anti-TNF therapy; non-melanoma skin cancer incidence was raised in RA, Ps and CD. In all indications, death rates were lower than, or equivalent to, those expected in the general population.

Conclusions Analysis of adverse events of interest through nearly 12 years of adalimumab exposure in clinical trials across indications demonstrated individual differences in rates by disease populations, no new safety signals and a safety profile consistent with known information about the anti-TNF class.

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  • Funding Abbott Laboratories sponsored the clinical trials and contributed to their design and data analysis.

  • Competing interests GRB has served as a consultant to Abbott Laboratories, Essex/Schering-Plough, Novartis and Roche and has received grants and honoraria from Abbott, Essex/Schering-Plough, Novartis, Roche, and Wyeth. RP has served as a consultant to Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Centocor, Elan, Ferring, GlaxoSmithKline, Procter and Gamble, Schering-Plough, Shire and UCB and has received grants from Abbott, Axcan, Bristol-Myers Squibb, Centocor, Elan, Millennium and Procter & Gamble and honoraria from Abbott Laboratories, Astra Zeneca, Byk Solvay, Centocor, Elan, Janssen, Procter and Gamble, Prometheus, Schering-Plough and Shire. KBG has received honoraria from and served as a consultant to Abbott Laboratories, Amgen, Centocor, Galderma, Pfizer, Merck and Lilly and has received grants from Abbott, Amgen, Centocor and Celgene. MJM and AL are employees of Abbott Laboratories and may hold stock or stock options.

  • Ethics approval National, regional, or investigative site ethics committees/institutional review boards, as appropriate.

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

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