{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:50:15Z","timestamp":1793155815611,"version":"4.5.0"},"reference-count":34,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2023,5,22]]},"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Despite several effective targeted therapies, biomarkers that predict whether a patient with psoriatic arthritis (PsA) will respond to a particular treatment are currently lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2023-003042","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T12:40:18Z","timestamp":1686832818000},"page":"e003042","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["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"],"prefix":"10.1136","volume":"9","clinical-trial-number":[{"clinical-trial-number":"nct01392326","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01752634","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01989468","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02294227","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02404350","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02745080","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01377012","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01350804","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01770379","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01392326","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01752634","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01989468","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02294227","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02404350","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02745080","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01377012","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01350804","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01770379","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5873-2632","authenticated-orcid":false,"given":"Mathias","family":"Cardner","sequence":"first","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"},{"name":"Novartis Institutes for BioMedical Research, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Tuckwell","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kostikova","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Forrer","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M","family":"Siegel","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Marti","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6407-3140","authenticated-orcid":false,"given":"Marc","family":"Vandemeulebroecke","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8362-100X","authenticated-orcid":false,"given":"Enrico","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"2025090313171322000_9.2.e003042.1","first-page":"S64","article-title":"Measures of Psoriatic arthritis: tender and swollen joint assessment, Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), Modified Nail Psoriasis Severity Index (mNAPSI), Mander\/Newcastle Enthesitis Index (MEI), Leeds Enthesitis Index (LEI), Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht Ankylosing Spondylitis Enthesis Score (MASES), Leeds Dactylitis Index (LDI), Patient Global for Psoriatic Arthritis, Dermatology Life Quality Index (DLQI), Psoriatic Arthritis Quality of Life (PsAQOL), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Psoriatic Arthritis Response Criteria (PsARC), Psoriatic Arthritis Joint Activity Index (PsAJAI), Disease Activity in Psoriatic Arthritis (DAPSA), and Composite Psoriatic Disease Activity Index (CPDAI)","volume":"63 Suppl 11","author":"Mease","year":"2011","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2025090313171322000_9.2.e003042.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30830-4"},{"key":"2025090313171322000_9.2.e003042.3","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1016\/S0140-6736(18)30949-8","article-title":"Clinical management of psoriatic arthritis","volume":"391","author":"Van den Bosch","year":"2018","journal-title":"Lancet"},{"key":"2025090313171322000_9.2.e003042.4","doi-asserted-by":"crossref","DOI":"10.1186\/s12967-021-02910-6","article-title":"Translational precision medicine: an industry perspective","volume":"19","author":"Hartl","year":"2021","journal-title":"J Transl Med"},{"key":"2025090313171322000_9.2.e003042.5","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1038\/s41591-022-01880-6","article-title":"The promise of precision medicine in rheumatology","volume":"28","author":"Guthridge","year":"2022","journal-title":"Nat Med"},{"key":"2025090313171322000_9.2.e003042.6","unstructured":"FDA-NIH Biomarker Working Group . BEST (biomarkers, endpoints, and other tools) resource. Silver Spring (MD): Food and Drug Administration (US), 2016."},{"key":"2025090313171322000_9.2.e003042.7","doi-asserted-by":"crossref","DOI":"10.1177\/1759720X211014010","article-title":"Biomarkers predictive of treatment response in psoriasis and psoriatic arthritis: a systematic review","volume":"13","author":"Magee","year":"2021","journal-title":"Ther Adv Musculoskelet Dis"},{"key":"2025090313171322000_9.2.e003042.8","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s40744-016-0039-x","article-title":"Secukinumab: a new treatment option for psoriatic arthritis","volume":"3","author":"Mease","year":"2016","journal-title":"Rheumatol Ther"},{"key":"2025090313171322000_9.2.e003042.9","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s40265-021-01476-3","article-title":"Secukinumab: a review in psoriatic arthritis","volume":"81","author":"Blair","year":"2021","journal-title":"Drugs"},{"key":"2025090313171322000_9.2.e003042.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1412679"},{"key":"2025090313171322000_9.2.e003042.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)61134-5"},{"key":"2025090313171322000_9.2.e003042.12","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-018-1551-x","article-title":"Efficacy and safety of secukinumab administration by autoinjector in patients with psoriatic arthritis: results from a randomized","volume":"20","author":"Nash","year":"2018","journal-title":"Arthritis Res Ther"},{"key":"2025090313171322000_9.2.e003042.13","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s40744-019-0163-5","article-title":"Efficacy and safety of subcutaneous secukinumab 150 mg with or without loading regimen in psoriatic arthritis: results from the FUTURE 4 study","volume":"6","author":"Kivitz","year":"2019","journal-title":"Rheumatol Ther"},{"key":"2025090313171322000_9.2.e003042.14","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-212687"},{"key":"2025090313171322000_9.2.e003042.15","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1016\/S0140-6736(20)30564-X","article-title":"Secukinumab versus Adalimumab for treatment of active Psoriatic arthritis (EXCEED): a double-blind, parallel-group, randomised, active-controlled, phase 3B trial","volume":"395","author":"McInnes","year":"2020","journal-title":"Lancet"},{"key":"2025090313171322000_9.2.e003042.16","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0015004","article-title":"Aptamer-based multiplexed proteomic technology for biomarker discovery","volume":"5","author":"Gold","year":"2010","journal-title":"PLoS One"},{"key":"2025090313171322000_9.2.e003042.17","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxj037"},{"key":"2025090313171322000_9.2.e003042.18","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380602"},{"key":"2025090313171322000_9.2.e003042.19","unstructured":"R Core Team . R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing, 2021. Available: https:\/\/www.R-project.org\/a language and environment for statistical co"},{"key":"2025090313171322000_9.2.e003042.20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9868.2005.00503.x"},{"key":"2025090313171322000_9.2.e003042.21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9868.2005.00503.x"},{"key":"2025090313171322000_9.2.e003042.22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9868.2010.00740.x"},{"key":"2025090313171322000_9.2.e003042.23","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1467-9868.2011.01034.x","article-title":"Variable selection with error control: another look at stability selection","volume":"75","author":"Shah","year":"2013","journal-title":"J R Stat Soc Ser B Stat Methodol"},{"key":"2025090313171322000_9.2.e003042.24","doi-asserted-by":"crossref","DOI":"10.1186\/s12859-015-0575-3","article-title":"Controlling false discoveries in high-dimensional situations: boosting with stability selection","volume":"16","author":"Hofner","year":"2015","journal-title":"BMC Bioinformatics"},{"key":"2025090313171322000_9.2.e003042.25","unstructured":"Therneau T , Atkinson B . rpart: recursive partitioning and regression trees. 2019. https:\/\/CRAN.R-project.org\/package=rpart"},{"key":"2025090313171322000_9.2.e003042.26","unstructured":"Kuhn M . Caret: classification and regression training. 2021. Available: https:\/\/CRAN.R-project.org\/package=caret"},{"key":"2025090313171322000_9.2.e003042.27","doi-asserted-by":"crossref","unstructured":"Wickham H . ggplot2: elegant graphics for data analysis. New York: Springer-Verlag, 2016. Available: https:\/\/ggplot2.tidyverse.org","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"2025090313171322000_9.2.e003042.28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708289200"},{"key":"2025090313171322000_9.2.e003042.29","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1016\/j.jid.2016.04.012","article-title":"Characterization of TNF-\u0391\u2013 and IL-17A\u2013mediated synergistic induction of DEFB4 gene expression in human keratinocytes through I\u03baB\u03b6","volume":"136","author":"Johansen","year":"2016","journal-title":"J Invest Dermatol"},{"key":"2025090313171322000_9.2.e003042.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.06.038"},{"key":"2025090313171322000_9.2.e003042.31","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/1346-8138.15278","article-title":"Assessment of serum biomarkers in patients with plaque psoriasis on secukinumab","volume":"47","author":"Morita","year":"2020","journal-title":"J Dermatol"},{"key":"2025090313171322000_9.2.e003042.32","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2022-eular.2468"},{"key":"2025090313171322000_9.2.e003042.33","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.237"},{"key":"2025090313171322000_9.2.e003042.34","doi-asserted-by":"crossref","DOI":"10.1186\/ar1038","article-title":"IL-17 induces production of IL-6 and IL-8 in rheumatoid arthritis synovial fibroblasts via NF-kappaB- and PI3-kinase\/AKT-dependent pathways","volume":"6","author":"Hwang","year":"2004","journal-title":"Arthritis Res Ther"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2023-003042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T20:17:22Z","timestamp":1756930642000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2023-003042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,6,15]]},"published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1136\/rmdopen-2023-003042"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2023-003042","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6]]}}}