Roccatello, Dario

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TYPE EditorialPUBLISHED 29 June 2023DOI 10.3389/fmed.2023.1242449OPEN ACCESSEDITED AND REVIEWED BYJoão Eurico Fonseca,University of Lisbon, Portugal*CORRESPONDENCEJavier Rodríguez-Carriorodriguezcjavier@uniovi.esRECEIVED 19 June 2023ACCEPTED 21 June 2023PUBLISHED 29 June 2023CITATIONAlunno A, Wincup C, Jani M, Roccatello D andRodríguez-Carrio J (2023) Editorial: Globalexcellence in rheumatology: Europe.Front. Med. 10:1242449.doi: 10.3389/fmed.2023.1242449COPYRIGHT© 2023 Alunno, Wincup, Jani, Roccatello andRodríguez-Carrio. This is an open-accessarticle distributed under the terms of theCreative Commons Attribution License (CC BY).The use, distribution or reproduction in otherforums is permitted, provided the originalauthor(s) and the copyright owner(s) arecredited and that the original publication in thisjournal is cited, in accordance with acceptedacademic practice. No use, distribution orreproduction is permitted which does notcomply with these terms.Editorial: Global excellence inrheumatology: EuropeAlessia Alunno1, Chris Wincup2,3, Meghna Jani4, Dario Roccatello5and Javier Rodríguez-Carrio6,7*1University of L’Aquila, MeSVA Department, Internal Medicine and Nephrology Division, ASL 1Avezzano-Sulmona-L’Aquila, L’Aquila, Italy, 2King’s College Hospital NHS Trust, London, United Kingdom,3Department of Rheumatology, University College London, London, United Kingdom, 4Centre forEpidemiology Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester,Manchester, United Kingdom, 5University Center of Excellence on Nephrologic, Rheumatologic andRare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member), Nephrology and Dialysis Unit andCenter of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the InterregionalNetwork for Rare Diseases of Piedmont and Aosta Valley (North-West Italy), Department of Clinical andBiological Sciences, University of Turin and San Giovanni Bosco Hub Hospital, ASL Città di Torino, Turin,Italy, 6Area of Immunology, Department of Functional Biology, Faculty of Medicine, University of Oviedo,Oviedo, Spain, 7Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, SpainKEYWORDSrheumatology, arthritis, machine learning, arthritis (including rheumatoid arthritis), lupusEditorial on the Research TopicGlobal excellence in rheumatology: EuropeRheumatology is a rapidly evolving specialty where major breakthroughs havebeen produced in recent years, from a paradigm change in clinical management ofrheumatic and musculoskeletal diseases (RMDs) to the discovery of novel drugs andbiological agents to manipulate the immune response in the context of autoimmunity andautoinflammation. European rheumatology is to be commended for its contribution tothe global excellence in rheumatology worldwide, including the development of evidence-based consensus recommendations for clinical management (1, 2), the development ofrobust methodologies to combine efforts from all stakeholders (rheumatologists, researchers,health professionals in rheumatology and people with RMDs) (3), the establishment ofinternational collaborations across European countries using registries and databases (4–6),and the harmonization of training programs (7). Several of these achievements can be largelyconnected to the leadership of a common entity, the European Alliance of RheumatologyAssociations (EULAR), who has served as an umbrella for clinical and research affairs inthis setting. The present Research Topic provides a summary of the European excellencein rheumatology, covering the whole range from clinical science to basic and translationalresearch, using a number of different approaches.The need for novel targets in RMDs is an area of constant research, with the aims notonly of establishing personalized medicine approaches but also to expand and refine thetherapeutic armamentarium. This point is addressed in the present Research Topic in a seriesof review articles focused on two of the most prevalent immune-mediated RMDs: systemiclupus erythematosus (SLE) and rheumatoid arthritis (RA). Parodis et al. comprehensivelysummarized the potential of B-cell altering therapeutics, including B-cells, B-cell relatedcytokines, and plasma cells, as well as combination strategies. A special emphasis is madein the promising role of B-cells as biomarkers to guide such strategies, with the aim ofmaximizing clinical benefit, although the exact readouts are yet to be identified. In the case ofFrontiers inMedicine 01 frontiersin.orgAlunno et al. 10.3389/fmed.2023.1242449RA, Gremese et al. advocated for the therapeutic potential of IL-8- and IL-17-targeted approaches based on the pathogenic role ofthese two molecules. In fact, this may explain at least in part theinadequate response of a proportion of RA patients to biologicaltherapies with other mechanisms of action. A series of elegantexperiments in animal and in vitro models as well as evidencefrom synovial studies reinforced this rationale, and candidateapproaches, such as bi-specific antibodies or JAK inhibitorsare discussed.Basic and translational science has been also instrumentalin expanding both the knowledge on RMDs pathogenesis andthe therapeutic armamentarium. Barker et al. have reported asignificant dysregulation of the mTOR pathway at synovial tissuelevel, also related to alterations in the Hippo-YAP pathway, leadingto immunometabolism traits. The inhibitory effect of rapamycinmay pave the ground for novel therapeutic strategies focused onthese pathways.The present Research Topic also showcases different examplesof excellence in clinical science. In benefit of solid, evidence-basedand good practices in research, the registration of study protocols(beyond industry-sponsored clinical trials) has become morefrequent in recent years, and it is usually mandatory for certaininstitution and funding agencies. Following this step, Rademacheret al. have presented their protocol to evaluate the feasibilityof rheopheresis for Raynaud’s syndrome and digital ulcers insystemic sclerosis, also including a number of secondary endpoints(from imaging to patient-reported outcomes). The results of thisapheresis approach are much awaited, since current evidence relieson retrospective studies or case reports, thus limiting clinicalapplication. Another clinical study has shed new light on a highlyrelevant, although usually less attended, topic in RMDs care: thework participation. Dejaco et al. demonstrated that treatment withgolimumab, a biological disease-modifying antirheumatic drug thatblocks TNF, led to a significant improvement in work productivityand activity in real-world patients with RA, psoriatic arthritisand axial spondyloarthritis, with no major differences across thethree patient groups. Although limited in follow-up (24 months),these results warrant further research into this area, with theultimate goal of reducing work impairment in people with RMDs.Whether work participation outcomes should be considered toguide treatment recommendations need to be considered infuture guidelines.Finally, it must be recognized how much artificial intelligenceand machine learning techniques are shaping our world and theway we interact with our environment, either in professionalor personal domains (8). The paper by Knitza et al. introduceshow machine learning approaches can be used to improve arheumatology referral system, by including laboratory parametersand enabling individual feature adaptations. In a system ofincreasing clinical pressure and overloaded staff, machine learningapproaches show promise to improve early referrals, a majorunmet need in the clinical care of RMDs. Additionally, it mayalso have several benefits in the implementation of telemedicinein rheumatology, particularly in the post-COVID-19 era. However,trials addressing cost-effectiveness, clinical validation and cross-cultural adaptations are needed.In summary, even in a challenging momentum for healthsystems, European rheumatology continues to show its hallmarksas a pioneer specialty. Multi-level approaches, high standards andsolid methodological procedures to solve complex questions andcover the whole disease process are the pillars of the excellenceof European rheumatology, with the ultimate goals of improvingclinical care and patients’ lives.Author contributionsJR-C edited the final version of the manuscript. All authorsdrafted, revised the manuscript, and approved the final version ofthe manuscript.FundingJR-C is supported by European Union FEDER funds andFondo de Investigación Sanitaria from Instituto de SaludCarlos III (ISCIII) (reference PI21/00054). MJ is funded bya National Institute for Health Research (NIHR) AdvancedFellowship (NIHR301413).Conflict of interestThe authors declare that the research was conducted in theabsence of any commercial or financial relationships that could beconstrued as a potential conflict of interest.Publisher’s noteAll claims expressed in this article are solely those of theauthors and do not necessarily represent those of their affiliatedorganizations, or those of the publisher, the editors and thereviewers. Any product that may be evaluated in this article, orclaim that may be made by its manufacturer, is not guaranteed orendorsed by the publisher.Author disclaimerThe views expressed in this publication are those of the authorsand not necessarily those of the NIHR, NHS or the UKDepartmentof Health and Social Care.References1. Smolen JS, Landewé RBM, Bergstra SA, Kerschbaumer A, Sepriano A, AletahaD, et al. EULAR recommendations for the management of rheumatoid arthritis withsynthetic and biological disease-modifying antirheumatic drugs: 2022 update. AnnRheum Dis. (2023) 82:3–18. doi: 10.1136/ard-2022-223356corr1Frontiers inMedicine 02 frontiersin.orgAlunno et al. 10.3389/fmed.2023.12424492. van der Heijde D, Ramiro S, Landewé R, Baraliakos X, Van den Bosch F, SeprianoA, et al. 2016 update of the ASAS-EULAR management recommendations for axialspondyloarthritis.Ann RheumDis. (2017) 76:978–91. doi: 10.1136/annrheumdis-2016-2107703. van der Heijde D, Aletaha D, Carmona L, Edwards CJ, KvienTK, Kouloumas M, et al. 2014 Update of the EULAR standardisedoperating procedures for EULAR-endorsed recommendations.Ann Rheum Dis. (2015) 74:8–13. doi: 10.1136/annrheumdis-2014-063504. Lauper K, Iudici M, Mongin D, Bergstra SA, Choquette D, Codreanu C,et al. Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitorsin 31 846 patients with rheumatoid arthritis in 19 registers from the ‘JAK-pot’collaboration. Ann Rheum Dis. (2022) 81:1358–66. doi: 10.1136/annrheumdis-2022-2225865. Gaggiano C, Vitale A, Tufan A, Ragab G, Aragona E, Wiesik-Szewczyk E, et al.The Autoinflammatory Diseases Alliance Registry of monogenic autoinflammatorydiseases. Front Med. (2022) 9:980679. doi: 10.3389/fmed.2022.9806796. Flores-Chavez A, Ng W-F, Alunno A, Inanc N, Feijoo-Massó C,Seror R, et al. Characterisation of the coexistence between sarcoidosis andSjögren’s syndrome. Analysis of 43 patients. Clin Exp Rheumatol. (2022)40:2329–2337. doi: 10.55563/clinexprheumatol/pg964c7. Alunno A, Avcin T, Haines C, Ramiro S, Sivera F, Badreh S, et al. Points toconsider: EULAR–UEMS standards for the training of European rheumatologists. AnnRheum Dis. (2023) 15:223941. doi: 10.1136/ard-2023-2239418. Kedra J, Radstake T, Pandit A, Baraliakos X, Berenbaum F, Finckh A,et al. Current status of use of big data and artificial intelligence in RMDs: asystematic literature review informing EULAR recommendations. RMD Open. (2019)5:e001004. doi: 10.1136/rmdopen-2019-001004Frontiers inMedicine 03 frontiersin.org

Editorial: Global excellence in rheumatology: Europe

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Editorial: Global excellence in rheumatology: Europe

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