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Applying precision medicine to unmet clinical needs in psoriatic disease

Abstract

Psoriatic disease (PsD) is a heterogeneous condition that can affect peripheral and axial joints (arthritis), entheses, skin (psoriasis) and other structures. Over the past decade, considerable advances have been made both in our understanding of the pathogenesis of PsD and in the treatment of its diverse manifestations. However, several major areas of continued unmet need in the care of patients with PsD have been identified. One of these areas is the prediction of poor outcome, notably radiographic outcome in patients with psoriatic arthritis, so that stratified medicine approaches can be taken; another is predicting response to the numerous current and emerging therapies for PsD, so that precision medicine can be applied to rapidly improve clinical outcome and reduce the risk of toxicity. In order to address these needs, novel approaches, including imaging, tissue analysis and the application of proteogenomic technologies, are proposed as methodological solutions that will assist the dissection of the critical immune-metabolic pathways in this complex disease. Learning from advances made in other inflammatory diseases, it is time to address these unmet needs in a multi-centre partnership aimed at improving short-term and long-term outcomes for patients with PsD.

Key points

  • Predicting outcome, in particular radiographic outcome, is a key unmet need in psoriatic arthritis (PsA), but although some individual markers seem promising, none has been validated in large clinical datasets.

  • Several new treatments targeting different pathways in PsA have improved outcomes, but many patients have persistent disease; a precision medicine approach to treatment choice is required.

  • Deep clinical phenotyping coupled with advances in imaging will help to better categorize patient status, an essential first step in the discovery of predictive biomarkers.

  • Molecular phenotyping of well-characterized patients and associated liquid and/or tissue biosamples is the next required step in trying to address these important areas of unmet need in PsA.

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Fig. 1: Model of pathobiology of psoriatic disease according to disease phenotypes.
Fig. 2: Structural sequelae of psoriatic arthritis mutilans.
Fig. 3: Bone remodelling in psoriatic arthritis.
Fig. 4: Micro-CT of small joints in psoriatic arthritis.
Fig. 5: High-resolution musculoskeletal ultrasound in psoriatic arthritis.

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All of the authors contributed to researching data for the article, made substantial contributions to discussion of the content, writing the manuscript and reviewing and/or editing the manuscript before submission.

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S.R.P. is founder of the UCD spin-out company Atturos. O.F. declares that he has received grants and/or honoraria from a number of pharmaceutical companies, including AbbVie, Amgen, Janssen, Lilly, Novartis, Pfizer and UCB. D.R.J. declares that he has received research/educational grants and/or honoraria from a number of pharmaceutical companies including AbbVie, Biogen, Celgene, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer and UCB. D.R.J. acknowledges support for research time from the Cambridge Arthritis Research Endeavour (CARE). C.S. declares that she has received honoraria from Janssen, Lilly and UCB, and has been supported by the National Institute for Health Research and the Cambridge Arthritis Research Endeavour (CARE).

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Jadon, D.R., Stober, C., Pennington, S.R. et al. Applying precision medicine to unmet clinical needs in psoriatic disease. Nat Rev Rheumatol 16, 609–627 (2020). https://doi.org/10.1038/s41584-020-00507-9

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