Y Cao1, F Hong2, D M Conlon3, L Sidur3, K M Smith4, Y Fang5, C A Cuff3, Z Kaymakcalan1, M C Ruzek3. 1. Immunology Discovery, AbbVie Bioresearch Center, Worcester, MA, 01605, USA. 2. Discovery and Early Pipeline Statistics, AbbVie Bioresearch Center, Worcester, MA, 01605, USA. 3. Translational Research, AbbVie Bioresearch Center, Worcester, MA, 01605, USA. 4. Immunology Systems Computational Biology, AbbVie Cambridge Research Center, Cambridge, MA, USA. 5. DMPK-BA, AbbVie Redwood City, CA, USA.
Abstract
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.
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.
Authors: Samuel Der Sarkissian; Schapoor Hessam; Joslyn S Kirby; Michelle A Lowes; Dillon Mintoff; Haley B Naik; Hans Christian Ring; Nisha Suyien Chandran; John W Frew Journal: JAMA Dermatol Date: 2022-03-01 Impact factor: 11.816
Authors: Gautham Vellaichamy; Anya T Amin; Peter Dimitrion; Zaakir Hamzavi; Li Zhou; Indra Adrianto; Qing-Sheng Mi Journal: Front Genet Date: 2022-08-26 Impact factor: 4.772