Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition

Abstract

Psoriasis is one of the most common chronic inflammatory skin diseases, affecting 3% of the world’s population, and approximately one-third of patients with psoriasis will eventually transition to having psoriatic arthritis (PsA). The evolution from cutaneous to synovio-entheseal inflammation in these patients presents an opportunity to investigate the critical events linked to arthritis development. The events responsible for progression to PsA are currently unclear. Genetic and clinical–demographic risk factors (most notably familial aggregation and psoriasis sub-phenotypes) provide relevant insights into the variables that promote transition. The specific underlying molecular and cellular mechanisms, however, remain poorly defined. Intriguingly, although targeting the IL-23–IL-17 axis substantially improves psoriasis outcomes, this strategy is not more effective than TNF inhibitors in improving musculoskeletal symptoms in PsA. Major unmet needs in the field of PsA include defining those patients with psoriasis at increased risk of developing arthritis, improving our understanding of the natural history of disease and characterizing the immune, environmental and molecular subclinical events preceding PsA onset. Improving our knowledge of this transition is essential for designing clinical trials with treatments that can delay, attenuate or even prevent the development of PsA in patients with psoriasis.

Key points

  • A revolution in the available treatments for psoriasis has led to beneficial clinical responses in a notable proportion of patients who very often achieve remission.

  • The therapeutic accomplishments in psoriasis, however, are yet to be matched in psoriatic arthritis (PsA), for which no new therapies have so far demonstrated superiority over established therapies.

  • Multiple strategies have been attempted to improve PsA outcomes, including earlier aggressive treatment and trying new targets or combinations of available therapeutics.

  • Once PsA is established, the inflammatory burden of psoriatic disease might not be susceptible to modulation in many patients.

  • Defining patients with psoriasis who are at increased risk of progression to PsA will enable studies to dissect the involvement of genetic, environmental and immune factors in PsA transition.

  • A predictive tool that uses integrated data from patients with psoriasis who are at increased risk of PsA progression should provide a framework for the design of preventive clinical trials.

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Fig. 1: Predictors of PsA.
Fig. 2: Transition from psoriasis to PsA: genes, immunity and environment.
Fig. 3: Factors conferring an increased risk of PsA development in patients with psoriasis.

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Acknowledgements

The work of J.U.S. is supported by grants from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (No. K23AR064318 and R03AR072182), The Riley Family Foundation, The Beatriz Snyder Foundation, the National Psoriasis Foundation and the Rheumatology Research Foundation. The work of A.O. is supported by the National Psoriasis Foundation, the Rheumatology Research Foundation and grants from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (No. K23AR063764 and R01AR072363). The work of C.R. is supported by grants from the National Psoriasis Foundation Discovery and the National Institutes of Health (No. R01AR069000).

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Nature Reviews Rheumatology thanks F. Behrens, D. Elewaut and other anonymous reviewer(s), for their contribution to the peer review of this work.

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Correspondence to Jose U. Scher or Christopher Ritchlin.

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J.U.S. has served as a consultant for Bristol-Myers Squibb, Janssen, Novartis and UCB and has received grants to the New York University School of Medicine from Novartis and Pfizer. A.O. has served as a consultant for Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer and Takeda and has received grants to the University of Pennsylvania from Novartis and Pfizer. J.F.M. is a consultant and/or investigator for Abbvie, Amgen, Biogen IDEC, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Samumed, Sanofi Regeneron and UCB. C.R. has received grants from Abbvie, Amgen and UCB. He is a consultant for Abbvie, Amgen, Janssen, Novartis, Pfizer and UCB.

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Scher, J.U., Ogdie, A., Merola, J.F. et al. Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition. Nat Rev Rheumatol 15, 153–166 (2019). https://doi.org/10.1038/s41584-019-0175-0

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