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The pathogenesis of rheumatoid arthritis: new insights from old clinical data?

Nature Reviews Rheumatology volume 8, pages 235–243 (2012)Cite this article

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Abstract

Despite their different targets, biologic agents used for blockade of TNF and IL-6, inhibition of T-cell co-stimulation and B-cell depletion all have similar beneficial effects on the outcome of rheumatoid arthritis (RA). This observation raises questions as to whether the targets of these therapies might all be involved in a common pathogenetic pathway. However, blockade of TNF and IL-6 has a similar inhibitory effect on joint damage progression in patients with either early or late disease. In comparison, B-cell depletion and inhibition of T-cell co-stimulation seem to have a somewhat delayed effect on joint damage (compared with cytokine inhibition), which suggests that these approaches affect upstream pathogenetic events. This article discusses these disparities and presents hypotheses as to whether clinical trial data can be used to determine at which point a biologic agent might interfere with the pathogenetic cascade in RA.

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Figure 1: Pathogenesis of RA.
Figure 2: The effects of TNF and IL-6 inhibition.
Figure 3: Effects of B-cell depletion on the pathogenesis of RA.
Figure 4: Effects of inhibiting T-cell co-stimulation on the pathogenesis of RA.
Figure 5: Changes in radiographic scores for RA after different biologic therapies.

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Acknowledgements

The authors are supported in part through Coordination Theme 1 (Health) of the European Community's FP7; Grant Agreement number HEALTH-F2-2008-223404 (Masterswitch). This is a publication of the Joint and Bone Center for Diagnosis, Research and Therapy of Musculoskeletal Disorders of the Medical University of Vienna, Austria.

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  1. Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, A-1090, Austria

    Josef S. Smolen, Daniel Aletaha & Kurt Redlich

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All authors researched the data for, and wrote, the manuscript as well as providing substantial contributions to discussions of the content and editing the article before submission.

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Correspondence to Josef S. Smolen.

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J. S. Smolen declares that he has acted as a speaker or consultant, and received research funding from Abbott, Amgen, Bristol-Myers Squibb, Janssen Biotech, MSD, Pfizer, Roche and UCB. D. Aletaha declares that he has acted as a speaker or consultant for Abbott, Bristol-Myers Squibb, MSD, Pfizer, Roche and UCB. K. Redlich declares that he has acted as a speaker or consultant for Abbott, MSD, Pfizer and Roche.

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Smolen, J., Aletaha, D. & Redlich, K. The pathogenesis of rheumatoid arthritis: new insights from old clinical data?. Nat Rev Rheumatol 8, 235–243 (2012). https://doi.org/10.1038/nrrheum.2012.23

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