Mortality rates in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors: Drug-specific comparisons in the Swedish Biologics Register

Authors

  • Julia F. Simard,

    Corresponding author
    1. Karolinska Institutet, Stockholm, Sweden
    • Clinical Epidemiology Unit T2, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden
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  • Martin Neovius,

    1. Karolinska Institutet, Stockholm, Sweden
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    • Dr. Neovius has received honoraria for Advisory Board service from Pfizer (less than $10,000).

  • Johan Askling,

    1. Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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    • Dr. Askling has received consulting fees, speaking fees, and/or honoraria from Merck, Abbott Laboratories, Pfizer, and Bristol-Myers Squibb (less than $10,000 each).

  • for the ARTIS Study Group


Abstract

Objective

To determine whether the differences in the modes of action and safety profiles of individual tumor necrosis factor inhibitors (TNFi) translate into differential mortality risks, as investigated in etanercept, infliximab, and adalimumab.

Methods

Data on patients with rheumatoid arthritis (RA) identified in the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden [ARTIS]) in whom first-ever treatment with a biologic agent (etanercept [n = 2,686], infliximab [n = 2,027], or adalimumab [n = 1,609]) was initiated between 2003 and 2008 were linked to national Swedish registers to get information on deaths from any cause, demographic features, RA characteristics, comorbid conditions, and concurrent treatment at the start of TNFi treatment. Hazard ratios (HRs) were modeled using multivariable adjusted and weighted Cox models.

Results

During 19,118 person-years of followup, 211 patients died (3.3%; 1.1 deaths per 100 person-years); 85% of the deaths occurred among patients who had been exposed to only one TNFi. We found no statistically significant difference in overall mortality rates across the exposure groups, regardless of adjustment and modeling approach (for infliximab versus etanercept, HR 1.1 [95% confidence interval (95% CI) 0.7–1.7], and for adalimumab versus etanercept, HR 1.3 [95% CI 0.9–2.0]).

Conclusion

Overall, we noted no statistically significant difference in mortality rates between the 3 TNF inhibitors under study. Further studies need to examine whether certain subsets of patients are at increased risk of death with specific TNFi.

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