How close are we to personalised medicine in psoriatic arthritis?

Personalised medicine aims to develop and determine the ideal drug or intervention for the individual patient. Prof. Ennio Lubrano (University of Molise, Italy) reviewed the evolution of personalised medicine and the use of biomarkers for patients with psoriatic arthritis.

Biomarkers are anatomical, serological, or physiological characteristics that can be measured objectively and can serve as indicators of normal or pathological disease processes and treatment interventions [1]. Biomarkers should be assessed for diagnosis, disease activity, prognosis, response to treatment, and comorbidities [2]. Although some studies assessed biomarkers such as Class I HLA, microRNA, serum proteins, and cytokines, “no arthritis-related biomarkers have been submitted to the FDA or EMA,” said Prof. Lubrano [3].

Currently, psoriatic disease treatment is seeing a shift towards personalised medicine. Based on initial data on clinical response and the immunophenotype characterised by activated Th1 and Th17 cells, a treatment algorithm was proposed in 2018 [4]. According to this algorithm, Th17-dominant patients should receive secukinumab, Th1/Th17-high patients with major joint involvement should receive TNF inhibition, Th1/Th17-high patients with major skin involvement should receive secukinumab, Th1/Th17-low patients should receive TNF inhibition, and the Th1-dominant group should receive ustekinumab. This treatment algorithm was more recently expanded with cell assessment based on peripheral immune cells, and updated from secukinumab to IL-17 inhibitors in general, and ustekinumab to IL-12/23(p40) inhibitors in general [5].

The researchers also used metabolomics analyses to identify potential biomarkers that can predict progression from psoriasis to psoriatic arthritis. The cross-sectional longitudinal registry IPART enrolled participants with psoriasis or psoriatic arthritis and healthy controls. The 71 participants included 16 healthy controls, 21 psoriasis non-progressors, 13 psoriatic arthritis progressors, and 21 participants with psoriatic arthritis (total). The analysis showed that participants with psoriatic arthritis had significantly lower serum levels of bile acids (i.e. glycoursodeoxycholic acid sulfate, glycodeoxycholate 3-sulfate, and deoxycholic acid 12-sulfate; P<0.001) as well as significantly higher levels of purine metabolites (P<0.01). Furthermore, when assessing psoriasis non-progressors and psoriatic arthritic progressors, multiple regression analyses found leukotriene B4 and glycoursodeoxycholic acid sulfate as significant predictors of progression. These results suggest that gut dysbiosis and altered hepatic metabolism could be causal factors for progression (immune cell proliferation and change in cytokine profile) [6].

“Precision medicine has not been sufficiently investigated in a real-world clinical setting [for psoriatic disease],” said Prof. Lubrano [1]. However, “the dawn of precision medicine is emerging.” Precision medicine is “not yet useful for single patients but data are coming from different clusters for determining biomarkers.”

1. 
   
   1. Biomarkers Definitions Working Group. Clin Pharmacol Ther. 2001;69(3):89-95.
   2. Mahendran SM, Chandran V. Proteomes. 2018;6(1):5.
   3. Lubrano E. Personalized medicine in psoriatic disease – where are we now and what are the unmet needs? IFPA Conference 2024, 27–29 June, Stockholm, Sweden.
   4. Al-Mossawi H, Coates LC. Nat Rev Rheumatol. 2018;4(8):449-451.
   5. Miyagawa I, Tanaka Y. Front Med (Lausanne). 2022;9:851892.
   6. Paine A, et al. Arthritis Rheumatol. 2023;75(1):53-63.

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Posted on 17 July 2024