Potential predictive biomarkers of adalimumab response in patients with hidradenitis suppurativa

Summary 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. What is already known about this topic? Adalimumab is the only approved treatment for patients with moderate‐to‐severe hidradenitis suppurativa (HS). In the PIONEER clinical studies, at least 50% of patients with HS achieved a clinical response by week 12 with maintenance through to week 168. What does this study add? We identified a potential predictive biomarker panel of plasma proteins for adalimumab response in patients with HS, as well as proteins that differentially respond to adalimumab in patients with HS. What is the translational message? The predictive panel of markers of adalimumab response in patients with HS could be adapted for clinical application and drive earlier and personalized treatment for patients with HS. Linked Comment: J.W. Frew. Br J Dermatol 2021; 185:696–697. Plain language summary a