{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T05:21:13Z","timestamp":1766726473172,"version":"3.48.0"},"reference-count":25,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"AIRC 2019","doi-asserted-by":"publisher","award":["23788"],"award-info":[{"award-number":["23788"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031478","name":"NextGenerationEU","doi-asserted-by":"crossref","award":["PNRR-MAD-2022-12375871"],"award-info":[{"award-number":["PNRR-MAD-2022-12375871"]}],"id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003196","name":"CUP","doi-asserted-by":"publisher","award":["J93C22002250006"],"award-info":[{"award-number":["J93C22002250006"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Serum calprotectin is a promising biomarker of inflammation in rheumatoid arthritis (RA), yet real-world longitudinal comparisons across different targeted therapies remain limited. We aimed to evaluate the dynamics and remission-predictive ability of serum calprotectin and C-reactive protein (CRP) in RA patients treated with adalimumab, upadacitinib, or tocilizumab. Methods: In this retrospective cohort study, patients with RA initiating one of the above therapies were included. Serum calprotectin and CRP were measured at baseline, month 3, and month 6. Disease activity was assessed by DAS28 and Clinical Disease Activity Index (CDAI). Linear mixed-effects models adjusted for cumulative prednisone dose were used to assess biomarker trends over time. ROC curve analyses based on CDAI remission (\u22642.8) evaluated the discriminative performance of calprotectin and CRP, stratified by treatment subgroups. Results: Sixty patients were enrolled (20 receiving tocilizumab, 20 adalimumab and 20 upadacitinib). Significant reductions in serum calprotectin, CRP, and DAS28 were observed over time (p &lt; 0.001 for all), independent of treatment group. In the overall cohort including baseline, CRP outperformed calprotectin (AUC 0.739 vs. 0.636; p = 0.044). Among patients treated with adalimumab or upadacitinib, calprotectin significantly outperformed CRP (AUC 0.929 vs. 0.857; p = 0.049). In the tocilizumab group, both biomarkers showed similar AUCs (p = 0.888). Conclusions: Serum calprotectin declined significantly after treatment initiation and outperformed CRP in identifying remission under TNF\u03b1 and JAK inhibition. It also retained a good performance under IL-6 blockade. These findings support its role as a treatment-sensitive biomarker suggesting a complementary role alongside CRP in RA monitoring, particularly in settings where CRP reliability is pharmacologically suppressed.<\/jats:p>","DOI":"10.3390\/diagnostics16010064","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T12:22:27Z","timestamp":1766578947000},"page":"64","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Comparison of Calprotectin and C-Reactive Protein in Rheumatoid Arthritis: Real-World Evidence Across Three Targeted Therapies"],"prefix":"10.3390","volume":"16","author":[{"given":"Angelo","family":"Fassio","sequence":"first","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isotta","family":"Galvagni","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Sartoris","sequence":"additional","affiliation":[{"name":"Immunology Unit, University Hospital of Verona, 37126 Verona, Italy"},{"name":"Immunology Section, Department of Medicine, University of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise Alessandra","family":"Cassandrini","sequence":"additional","affiliation":[{"name":"Immunology Unit, University Hospital of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3965-5295","authenticated-orcid":false,"given":"Federico","family":"Aldegheri","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9692-2293","authenticated-orcid":false,"given":"Maurizio","family":"Rossini","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1691-2196","authenticated-orcid":false,"given":"Francesco","family":"Pollastri","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Adami","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7471-3076","authenticated-orcid":false,"given":"Davide","family":"Gatti","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosanna","family":"Somma","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Appoloni","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Carletto","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3741-5141","authenticated-orcid":false,"given":"Vincenzo","family":"Bronte","sequence":"additional","affiliation":[{"name":"Immunology Unit, University Hospital of Verona, 37126 Verona, Italy"},{"name":"Immunology Section, Department of Medicine, University of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5567-4190","authenticated-orcid":false,"given":"Alessandra","family":"Arcolaci","sequence":"additional","affiliation":[{"name":"Immunology Unit, University Hospital of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1056\/NEJMra2103726","article-title":"Rheumatoid Arthritis\u2014Common Origins, Divergent Mechanisms","volume":"388","author":"Gravallese","year":"2023","journal-title":"N. 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