Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: The role of acute-phase reactants

Authors

  • Josef S. Smolen,

    Corresponding author
    1. Medical University of Vienna and Hietzing Hospital, Vienna, Austria
    • Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
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    • Dr. Smolen has received consulting fees, speaking fees, and/or honoraria from Abbott, Amgen, Bristol-Myers Squibb, Centocor, Schering-Plough, Roche, UCB, and Wyeth (less than $10,000 each).

  • Daniel Aletaha

    1. Medical University of Vienna, Vienna, Austria
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    • Dr. Aletaha has received consulting fees, speaking fees, and/or honoraria from Bristol-Myers Squibb, Roche, UCB, Abbott, Wyeth, and Schering-Plough (less than $10,000 each).


Abstract

Objective

To determine the effects of tocilizumab on rheumatoid arthritis (RA) disease activity and remission assessment, using measures that do or do not comprise acute-phase reactants.

Methods

Simplified Disease Activity Index (SDAI) scores, Clinical Disease Activity Index (CDAI) scores, and the Disease Activity Score in 28 joints (DAS28) were calculated using data from tocilizumab trials in patients with RA in whom disease had remained active despite treatment with disease-modifying antirheumatic drugs. The CDAI does not contain an acute-phase reactant component. Disease activity states, including remission, were defined using established cut points; for the DAS28, an alternative cut point of <2.4 was also used.

Results

Changes in the DAS28, the SDAI score, and the CDAI score among patients receiving tocilizumab were significantly higher than those among patients receiving placebo, and the magnitude of these changes was similar for the SDAI and the CDAI. Among patients who achieved 50% improvement in disease activity according to the American College of Rheumatology criteria, only ∼20% required a reduction in acute-phase reactant values in order to fulfill the criteria. However, DAS28 remission rates were higher (even when using the lower cut point) than the SDAI and CDAI remission rates. Only a minority of tocilizumab-treated patients with DAS28 remission also had disease remission according to the SDAI (26%) or CDAI (∼21%). With infliximab treatment, SDAI and CDAI remission rates were of the same magnitude as those observed with tocilizumab treatment, and DAS28 remission rates were lower. Tocilizumab-treated patients with DAS28 remission but without CDAI remission had significantly higher swollen joint counts but lower erythrocyte sedimentation rates (ESRs) compared with patients with SDAI or CDAI remission.

Conclusion

Disease activity in RA is reduced by tocilizumab treatment, irrespective of the type of composite measure used to evaluate disease activity. Remission rates were much higher using the DAS28 compared with the SDAI and CDAI, due to the high weight of the ESR in the DAS28 and the effect of tocilizumab on the ESR. Using the stringent SDAI and CDAI criteria, however, remission rates in patients treated with tocilizumab were in the same range as those seen in patients treated with tumor necrosis factor inhibitors.

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