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.

Objectives: Despite several effective targeted therapies, biomarkers that predict whether a patient with psoriatic arthritis (PsA) will respond to a particular treatment are currently lacking.
Methods: We analysed proteomics data from serum samples of nearly 2000 patients with PsA in placebo-controlled phase-III clinical trials of the interleukin-17 inhibitor secukinumab. To discover predictive biomarkers of clinical response, we used statistical learning with controlled feature selection. The top candidate was validated using an ELISA and was separately assessed in a trial of almost 800 patients with PsA treated with secukinumab or the tumour necrosis factor inhibitor adalimumab.
Results: Serum levels of beta-defensin 2 (BD-2) at baseline were found to be robustly associated with subsequent clinical response (eg, American College of Rheumatology definition of 20%, 50% and 70% improvement) to secukinumab, but not to placebo. This finding was validated in two independent clinical studies not used for discovery. Although BD-2 is known to be associated with psoriasis severity, the predictivity of BD-2 was independent of baseline Psoriasis Area and Severity Index. The association between BD-2 and response to secukinumab was observed as early as 4 weeks and maintained up to 52 weeks. BD-2 was also found to predict response to treatment with adalimumab. Unlike in PsA, BD-2 was not predictive of response to secukinumab in rheumatoid arthritis.
Conclusions: In PsA, BD-2 at baseline is quantitatively associated with clinical response to secukinumab. Patients with high levels of BD-2 at baseline reach and sustain higher rates of clinical response after treatment with secukinumab.
Competing Interests: Competing interests: All authors are employees of Novartis AG, except MC who is now employed by AstraZeneca AB. AK, PF, RMS, AM, MV and EF hold Novartis shares or share options. Unrelated to this work, RMS has acted as a consultant for Boxer Capital LLC, and PF serves as a guest lecturer for the University of Applied Sciences Northwestern Switzerland.
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