{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:32:37Z","timestamp":1787761957487,"version":"build-2784847793"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The study aims to evaluate the applicability of the D2T psoriatic arthritis (PsA) definition, adapted from rheumatoid arthritis, within a single-center observational cohort of PsA patients treated with b\/tsDMARDs. In addition, we aimed to establish a numerical index defining D2T-PsA based on the ratio of observed to expected failed b\/tsDMARDs and to develop a predictive model identifying features associated with the D2T condition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study included 267 consecutive adult PsA patients receiving b\/tsDMARDs, collecting demographic, clinical, and clinimetric data. The prevalence of D2T PsA patients was assessed using a proposed definition. We then developed a predictive model to assess treatment difficulty, utilizing PsA-normalized failed b\/tsDMARDs. A generalized linear model was applied to identify clinical and demographic features associated with D2T PsA, employing a bagging procedure for robust variable selection, followed by univariate and multivariable analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 267 patients, only 8 of them (2.9%) met the proposed D2T PsA criteria. In a subset of 177 patients analyzed using the predictive model, 17.2% of them demonstrated higher treatment difficulty. Univariate analysis revealed associations between treatment difficulty and female sex, psoriasis pattern, fibromyalgia, and steroid therapy. Multivariate analysis confirmed significant associations between fibromyalgia, nail and pustular psoriasis, and steroid use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>According to the predictive model, the proposed D2T PsA definition identified a small subset of patients with increased treatment difficulty. These findings highlight the need for refining the criteria to better define D2T PsA patients, providing valuable insights into managing complex treatment challenges in PsA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2024.1509082","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T04:19:30Z","timestamp":1734322770000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Difficult-to-treat psoriatic arthritis: refining the definition using a statistical model in a real-life cohort"],"prefix":"10.3389","volume":"11","author":[{"given":"Ennio Giulio","family":"Favalli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Biganzoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilberto","family":"Cincinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Ferrito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Luconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Manara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Biggioggero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Boracchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Caporali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/s41584-022-00874-5","article-title":"Phenotypic heterogeneity in psoriatic arthritis: towards tissue pathology-based therapy","volume":"19","author":"Najm","year":"2023","journal-title":"Nat Rev Rheumatol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1016\/S0140-6736(15)00347-5","article-title":"Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicentre, open-label, randomized controlled trial","volume":"386","author":"Coates","year":"2015","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1136\/annrheumdis-2020-217159","article-title":"EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update","volume":"79","author":"Gossec","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s41584-022-00798-0","article-title":"Group for Research and Assessment of psoriasis and psoriatic arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021","volume":"18","author":"Coates","year":"2022","journal-title":"Nat Rev Rheumatol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3899\/jrheum.170449","article-title":"Minimal disease activity as a treatment target in psoriatic arthritis: a review of the literature","volume":"45","author":"Gossec","year":"2018","journal-title":"J Rheumatol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e003809","DOI":"10.1136\/rmdopen-2023-003809","article-title":"Difficult-to-treat psoriatic arthritis (D2T PsA): a scoping literature review informing a GRAPPA research project","volume":"10","author":"Singla","year":"2024","journal-title":"RMD Open"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"105062","DOI":"10.1016\/j.jbspin.2020.07.011","article-title":"Golimumab effectiveness in biologic inadequate responding patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis in real-life from the Italian registry GISEA","volume":"88","author":"Iannone","year":"2021","journal-title":"Joint Bone Spine"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"76","DOI":"10.4081\/reumatismo.2023.1544","article-title":"Retention rate of tumor necrosis factor inhibitors, anti-interleukin 17, and anti-interleukin 12\/23 drugs in a single-center cohort of psoriatic arthritis patients","volume":"75","author":"Ferrito","year":"2023","journal-title":"Reumatismo"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1136\/annrheumdis-2020-217344","article-title":"EULAR definition of difficult-to-treat rheumatoid arthritis","volume":"80","author":"Nagy","year":"2021","journal-title":"Ann Rheum Dis"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1007\/s40744-022-00461-w","article-title":"Clinical characteristics of potential \u2018difficult-to-treat\u2019 patients with psoriatic arthritis: a retrospective analysis of a longitudinal cohort","volume":"9","author":"Perrotta","year":"2022","journal-title":"Rheumatol Ther"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"152275","DOI":"10.1016\/j.semarthrit.2023.152275","article-title":"Characteristics of difficult-to-treat psoriatic arthritis: a comparative analysis","volume":"63","author":"Philippoteaux","year":"2023","journal-title":"Semin Arthritis Rheum"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"985","DOI":"10.3899\/jrheum.2024-0101","article-title":"Difficult-to-treat concept in psoriatic arthritis: analysis of 2 potential definitions in a large Group of Patients. A Cross-Sectional Study","volume":"51","author":"Perrotta","year":"2024","journal-title":"J Rheumatol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1007\/s10067-023-06605-9","article-title":"Difficult to treat psoriatic arthritis \u2014 how should we manage?","volume":"42","author":"Kumthekar","year":"2023","journal-title":"Clin Rheumatol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"2427","DOI":"10.1093\/rheumatology\/keae263","article-title":"Identification and characteristics of patients with potential difficult-to-treat psoriatic arthritis: exploratory analyses of the Greek PsA registry","volume":"63","author":"Vassilakis","year":"2024","journal-title":"Rheumatology"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1002\/art.42780","article-title":"Difficult-to-treat psoriatic arthritis: a conceptual approach","volume":"76","author":"Fagni","year":"2024","journal-title":"Arthritis Rheumatol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"4569","DOI":"10.1007\/s10067-021-05799-0","article-title":"Predictive factors for switching in patients with psoriatic arthritis undergoing anti-TNF\u03b1, anti-IL12\/23, or anti-IL17 drugs: a 15-year monocentric real-life study","volume":"40","author":"Lorenzin","year":"2021","journal-title":"Clin Rheumatol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1007\/s00296-021-04925-0","article-title":"Fibromyalgia influences health-related quality of life and disease activity in psoriatic arthritis","volume":"42","author":"Kancharla","year":"2022","journal-title":"Rheumatol Int"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"917939","DOI":"10.3389\/fimmu.2022.917939","article-title":"A machine learning approach to predict remission in patients with psoriatic arthritis on treatment with Secukinumab","volume":"13","author":"Venerito","year":"2022","journal-title":"Front Immunol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1007\/s10067-017-3769-4","article-title":"A 2-year observational study on treatment targets in psoriatic arthritis patients treated with TNF inhibitors","volume":"36","author":"Chimenti","year":"2017","journal-title":"Clin Rheumatol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1093\/rheumatology\/kew326","article-title":"The influence of obesity on response to tumour necrosis factor-\u03b1 inhibitors in psoriatic arthritis: results from the DANBIO and ICEBIO registries","volume":"55","author":"H\u00f8jgaard","year":"2016","journal-title":"Rheumatol Oxf Engl"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"475","DOI":"10.3899\/jrheum.171034","article-title":"Predictors of achieving remission among patients with psoriatic arthritis initiating a tumor necrosis factor inhibitor","volume":"46","author":"Ogdie","year":"2019","journal-title":"J Rheumatol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1016\/j.semarthrit.2020.01.012","article-title":"Remission in psoriatic arthritis: definition and predictors","volume":"50","author":"Alharbi","year":"2020","journal-title":"Semin Arthritis Rheum"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e42","DOI":"10.1136\/annrheumdis-2020-217251","article-title":"Secukinumab efficacy in patients with PsA is not dependent on patients\u2019 body mass index","volume":"81","author":"Pantano","year":"2022","journal-title":"Ann Rheum Dis"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.jaad.2014.04.063","article-title":"Palmoplantar psoriasis is associated with greater impairment of health-related quality of life compared with moderate to severe plaque psoriasis","volume":"71","author":"Chung","year":"2014","journal-title":"J Am Acad Dermatol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/1756-185X.14442","article-title":"The impact of nail psoriasis on disease activity, quality of life, and clinical variables in patients with psoriatic arthritis: a cross-sectional multicenter study","volume":"26","author":"Cengiz","year":"2023","journal-title":"Int J Rheum Dis"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1007\/s40744-020-00221-8","article-title":"Disease characteristics and the burden of joint and skin involvement amongst people with psoriatic arthritis: a population survey","volume":"7","author":"Tillett","year":"2020","journal-title":"Rheumatol Ther"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41584-024-01083-y","article-title":"Difficult-to-treat psoriatic arthritis: moving out of the rheumatoid arthritis shadow","volume":"20","author":"Siebert","year":"2024","journal-title":"Nat Rev Rheumatol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"152134","DOI":"10.1016\/j.semarthrit.2022.152134","article-title":"Comparison of disease activity index for psoriatic arthritis (DAPSA) and minimal disease activity (MDA) targets for patients with psoriatic arthritis: a post hoc analysis of data from phase 3 tofacitinib studies","volume":"58","author":"Schneeberger","year":"2023","journal-title":"Semin Arthritis Rheum"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"rkac 057","DOI":"10.1093\/rap\/rkac057","article-title":"Single-center experience of refractory rheumatoid arthritis","volume":"6","author":"Fitton","year":"2022","journal-title":"Rheumatol Adv Pract"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/s41584-020-00541-7","article-title":"Persistent inflammatory and non-inflammatory mechanisms in refractory rheumatoid arthritis","volume":"17","author":"Buch","year":"2021","journal-title":"Nat Rev Rheumatol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1007\/s40744-023-00574-w","article-title":"Difficult to treat and refractory to treatment in psoriatic arthritis","volume":"10","author":"Lubrano","year":"2023","journal-title":"Rheumatol Ther"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1509082\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T04:19:33Z","timestamp":1734322773000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1509082\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,16]]},"references-count":31,"alternative-id":["10.3389\/fmed.2024.1509082"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2024.1509082","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,16]]},"article-number":"1509082"}}