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Potential predictive biomarkers of adalimumab response in patients with hidradenitis suppurativa
Y Cao1, F Hong2, D M Conlon3
1Immunology Discovery, AbbVie Bioresearch Center, Worcester, MA, 01605, USA.
Background:
Adalimumab provides significant efficacy for patients with hidradenitis suppurativa (HS), which was demonstrated by at least 50% of patients achieving a clinical response by week 12 that was maintained through to week 168 in the PIONEER trials.
Objectives:
To identify whether there are biomarkers that could predict adalimumab response, as well as markers that differentially respond to adalimumab in patients with HS.
Methods:
Baseline and week-12 plasma samples from the PIONEER studies were used to assess the levels of circulating proteins by multiplex and enzyme-linked immunosorbent assays.
Results:
Analyses revealed significantly higher high-sensitivity C-reactive protein (hs-CRP) and chemokine (C-C motif) ligand (CCL) 16 (HCC-4) levels in nonresponders at baseline and identified a multivariate response signature of calprotectin, fractalkine and HCC-4, reaching an 86% predictive accuracy rate for adalimumab response. Additionally, post-treatment reduction of plasma C-X-C motif chemokine ligand (CXCL)9, CXCL8 (interleukin-8) and CCL19 (macrophage inflammatory protein 3β) were greater in adalimumab super-responders than in nonresponders (P = 0·026, P = 0·044 and P = 0·026, respectively). These cytokines are involved in the recruitment of innate and adaptive inflammatory cells, and/or stimulation of certain inflammatory responses, suggesting that these pathways could be disease drivers in adalimumab nonresponders.
Conclusions:
These initial results suggest HCC-4, calprotectin and fractalkine could be potential predictive biomarkers of adalimumab response in HS and identified possible tumour necrosis factor-independent disease pathways.
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