Potential predictive biomarkers of adalimumab response in patients with hidradenitis suppurativa*
| Autor: | Z. Kaymakcalan, Yonghao Cao, D M Conlon, L Sidur, F Hong, Carolyn A. Cuff, Y Fang, Melanie C. Ruzek, Kristine M. Smith |
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| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
Oncology medicine.medical_specialty Chemokine Carcinoma Hepatocellular Necrosis Anti-Inflammatory Agents Dermatology 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Internal medicine Adalimumab medicine Humans Hidradenitis suppurativa Interleukin 8 Macrophage inflammatory protein biology business.industry Liver Neoplasms CCL19 medicine.disease Hidradenitis Suppurativa Treatment Outcome biology.protein medicine.symptom Calprotectin business Biomarkers medicine.drug |
| Zdroj: | British Journal of Dermatology. 185:804-814 |
| ISSN: | 1365-2133 0007-0963 |
| DOI: | 10.1111/bjd.20097 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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