COMMENTARY

Identifying Preclinical Psoriatic Arthritis in Hope of Prevention

Kevin D. Deane, MD, PhD

Disclosures

May 31, 2017

The Development of Psoriatic Arthritis in Patients With Psoriasis Is Preceded by a Period of Nonspecific Musculoskeletal Symptoms: A Prospective Cohort Study

Eder L, Polachek A, Rosen CF, Chandran V, Cook R, Gladman DD
Arthritis Rheumatol. 2017;69:622-629

Study Summary

Eder and colleagues followed 410 subjects who had psoriasis but not psoriatic arthritis (PsA) at baseline, according to a rheumatologist's evaluation. Over a mean follow-up period of approximately 46 months, 57 (13.9%) of these subjects developed PsA as defined by the Classification of Psoriatic Arthritis criteria,[1] which could include both axial and peripheral arthritis.

The authors found that a variety of musculoskeletal symptoms preceded an identification of PsA by approximately 6 years. The strongest predictors at baseline for the future development of PsA were heel pain, high fatigue, and high stiffness—in particular, back stiffness. Furthermore, arthralgia of any kind was a significant predictor for future PsA in women but not men. The extent of skin involvement as assessed by Psoriasis Area and Severity Index was associated with only a minimal risk for future PsA (hazard ratio, 1.05; 95% confidence interval, 1.01-1.09). Body mass index and nail pitting were not associated with future PsA.

Viewpoint

There is growing evidence that several rheumatic diseases, including rheumatoid arthritis and systemic lupus erythematosus, have a "preclinical" period of development that can be identified by serologic markers and, in some cases, symptoms.[2] Indeed, this has led to several prevention trials in rheumatoid arthritis.[3]

These findings by Eder and colleagues strongly suggest that PsA also has a "preclinical" period and raise the idea that perhaps PsA could be targeted for prevention. Of note, given that PsA is typically also preceded by skin disease,[4] it may be an ideal condition in which to develop possible preventive approaches because these patients are easier to identify for participation in clinical settings. Given that they already have clinically apparent disease, it will also be easier to apply preventive therapy than in, say, someone who lacks any clinical evidence of a disease.

Critical next steps will be to develop and validate robust models for prediction of PsA, which must be applicable in settings such as dermatology clinics where patients with psoriasis may initially present (and especially given the growing shortfall in rheumatologists). These prediction models should also include biomarkers that may consist of genetic factors such as HLAB27 as well as imaging. Furthermore, other blood-based biomarkers beyond genetics need to be considered in predicting future PsA. This is because although PsA has long been considered a "seronegative" disease, there is increasing understanding that it is associated with numerous systemic biomarkers including inflammatory markers (eg, interleukin-6), markers of cartilage injury (eg, cartilage oligomeric matrix protein), microRNAs, and circulating osteoclast precursors.[5,6]

Of note, there may already exist "proof" that PsA can be prevented. Specifically, it may well be that patients with psoriasis who receive therapy for their skin disease such as methotrexate, anti-tumor necrosis factor agents, or other biologics (eg, ustekinumab) have less progression to PsA. Eder and colleagues did not address this issue in their paper, but other clinic registries should attempt to do so, especially because these data will provide powerful support for the development of novel clinical prevention trials.

Abstract

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