Not your average joint: Towards precision medicine in psoriatic arthritis

Abstract

Precision medicine, propelled by advances in multi-omics methods and analytics, aims to revolutionize patient care by using clinically-actionable molecular markers to guide diagnostic and therapeutic decisions. We describe the applications of precision medicine in risk stratification, drug selection, and treatment response prediction in psoriatic arthritis, for which targeted, personalized approaches are steadily emerging.

Introduction

From the time of Hippocrates to today's hyper-specialized era, the practice of medicine has relied on the same method for disease classification and diagnosis: pattern recognition based on the average, archetypal patient [[1], [2], [3], [4], [5]]. “Average” used to be the benchmark that guided every medical decision. However, whereas the elements that defined “average” have been historically limited to clinical signs and symptoms of a pathological process, the technological and analytic advances over the last two decades have led to the incorporation of big multi-omics data to discern inter-individual differences at a molecular scale. This, in turn, is paving the way for the development of more rigorous and definitive disease taxonomies and phenotypes. Our ever-evolving capacity to harness big data from high throughput approaches has made it possible to dissect and characterize disease heterogeneity. It has also helped determine the drivers of treatment response or refractoriness, allowing us to veer away from an empiric, one-size-fits-all approach to a more targeted, individualized strategy that abandons the concept of “average” espoused by traditional medicine in favor of what is known as precision medicine [6].

The applications of precision medicine are far-reaching and span the spectrum of health and illness. At its core, it relies on the use of biomarkers derived primarily from blood and affected tissues to aid in risk stratification, disease classification, and drug response prediction (Fig. 1). In recognition of these broad benefits and enormous potential, the Precision Medicine Initiative was launched in 2015 with the goal of “accelerating biomedical discoveries and providing clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients [7,8].”

While an individualized approach is imminently beneficial in all aspects of medicine, one group of disorders for which precision medicine is most critically needed are chronic, immune-mediated diseases which are notoriously heterogenous and typically require lifelong treatment. Psoriatic arthritis (PsA), a chronic, potentially disabling inflammatory arthritis that is characterized by several distinct clinical phenotypes, is one such condition.

Occurring in up to 30% of patients with psoriasis, PsA affects the axial skeleton, peripheral joints, and entheses [9,10]. Because patients with PsA have concomitant skin and synovioentheseal disease, the burden of illness in PsA-affected individuals compared to those with skin-limited PsO is conceivably greater, with studies showing more profound impact on quality of life (QOL), function, disability, and unemployment [[11], [12], [13]]. Moreover, psoriatic disease is linked to a myriad of extraarticular manifestations and comorbidities such as ocular inflammation, cardiovascular disease, diabetes, obesity, inflammatory bowel disease, thyroid dysfunction, and mood disorders [[14], [15], [16], [17], [18]]. Thus, the utility of precision medicine's mantra of providing “the right drug for the right patient at the right time” rings particularly true for those afflicted with PsA.