Higher Levels Of Beta-Defensin 2 may Improve Clinical Response In Psoriatic Arthritis Patients Treated With Secukinumab

A recent study published in Rheumatic and Musculoskeletal Diseases has identified a potential biomarker that could help predict the response to treatment in patients with psoriatic arthritis (PsA). The study found that higher levels of beta-defensin 2 (BD-2) at baseline were associated with better clinical response to secukinumab, an interleukin-17 inhibitor used in the treatment of PsA.

Psoriatic arthritis is a chronic inflammatory condition that affects the joints and is often accompanied by skin and nail psoriasis. While there are effective targeted therapies available for PsA, there is a lack of biomarkers that can accurately predict treatment response in this patient population. Approximately 4 out of 10 patients with PsA do not respond adequately to cytokine inhibitors, and only 6 out of 10 patients achieve a 20% improvement in clinical outcomes.

The researchers Cardener M and team analyzed proteomics data obtained from serum samples of 1989 patients diagnosed with psoriatic arthritis (PsA). These patients were enrolled in various placebo-controlled phase 3 clinical trials, including FUTURE 1-5 and EXCEED, which investigated the efficacy of secukinumab, an inhibitor of interleukin-17 (IL-17). Additionally, the researchers examined phase 3 trials for rheumatoid arthritis (RA), namely REASSURE, REASSURE 2, and NURTURE 1, as part of their evaluation.

● The findings revealed that higher levels of BD-2 in the serum at baseline were significantly associated with better clinical response, as measured by the American College of Rheumatology (ACR) 20%, 50%, and 70% improvement rates.

● The predictive value of BD-2 was independent of the baseline Psoriasis Area and Severity Index (PASI), which is commonly used to assess psoriasis severity.

● The results were further validated in independent clinical studies, and BD-2 was found to be the only secukinumab-specific biomarker selected for prediction of response.

● The association between BD-2 levels and treatment response was observed as early as 4 weeks into treatment and was sustained up to 52 weeks.

● BD-2 levels also predicted response to adalimumab, a tumour necrosis factor inhibitor used in the treatment of PsA.

It is important to note that BD-2 levels did not predict response to secukinumab in a separate analysis of patients with RA. In psoriasis cohorts, the data were inconclusive, possibly due to the small sample sizes used in those studies.

The researchers suggest that these findings indicate the presence of an IL-17-driven endotype of PsA characterized by higher levels of serum BD-2 and a greater response to secukinumab treatment. This opens up possibilities for precision medicine approaches in addressing the remaining unmet medical needs in PsA.

Further research and validation studies are needed to confirm the utility of BD-2 as a predictive biomarker for treatment response in PsA. If confirmed, this biomarker could aid in

the selection of appropriate therapies for individual patients, improving the overall management of PsA and potentially leading to better treatment outcomes.

Reference:

Cardner M, Tuckwell D, Kostikova A, et al. Analysis of serum proteomics data identifies a quantitative association between beta-defensin 2 at baseline and clinical response to IL-17 blockade in psoriatic arthritis. RMD Open. 2023;9(2):e003042. doi:10.1136/rmdopen-2023-003042.