Predicting therapeutic response through biomarker analysis in psoriatic arthritis, an example of precision medicine

ABSTRACT

Introduction: Psoriatic arthritis (PsA) is a heterogeneous inflammatory arthritis for which effective targeted therapies are now available. However, despite such advances up to 40% of patients fail to meet the primary endpoint in clinical trials. Current approach to therapy does not take it account clinical or molecular heterogeneity and is based on trial-and-error. It is envisioned that choosing therapies based on appropriate molecular biomarker profiles will help choose the appropriate therapy for a patient and as such lead to better treatment outcomes with reduced costs and less exposure to less effective therapies.

Areas covered: The paper introduces PsA and briefly describes the clinical phenotype, pathogenesis, and current therapies. Current literature on biomarkers relating to PsA treatment response is reviewed. Limitations of the current approach, potential solutions to issues identified, and a path forward for research and potential clinical application in this area are discussed.

Expert opinion: The likelihood that the current siloed approach to biomarker discovery will lead to meaningful clinically actionable tests to facilitate precision medicine in PsA is low. We envision that with collaborative and harmonized effort by all stakeholders using an inter-omic approach will lead to the development of robust predictive biomarkers for PsA treatment response.

KEYWORDS:

• Inter-omics
• spondyloarthritis
• targeted therapy

Article highlights

• Psoriatic arthritis is a heterogeneous inflammatory musculoskeletal disease, a spondyloarthritis, associated with psoriasis.

• In pivotal clinical trials with targeted therapies, about 60% of patients meet the primary endpoint.

• Current clinical practice is to choose therapies based on response from pooling of patients, using a trial-and-error approach; individual molecular features are not currently taken into account when choosing therapy.

• Th-17 cells and Th-17 mediated cytokines play a critical role in PsA disease pathology.

• With the emergence of newer-targeted therapies with different mechanisms of action, establishing patterns of response is now an urgent issue for the clinician, as is the identification of subgroups of patients who may differ in response patterns to these therapies.

• Relatively small, mostly unverified studies have identified modest genetic, mRNA, miRNA, protein, tissue, and cellular biomarkers associated with response to currently available therapies in PsA.

• Better definition of clinical response for biomarker studies, harmonized collection of clinical data and biospecimens, data integration, analysis, and management as well as adequate financial resources is presently needed.

• Public-private collaboration such as that through the Accelerating Medicines Partnership will likely be required to achieve the goals for precision medicine in PsA.

Declaration of interest

Vinod Chandran has received honoraria from Amgen, Abbvie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB; and research grants from Abbvie and Celgene. Spouse is an employee of Eli Lilly. Proton Rahman has received honoraria from Amgen, Abbott, AbbVie, BMS, Celgene, Eli Lilly, Janssen, Pfizer, Novartis, Merck and UCB; and research grants from Novartis and Janssen.