Location and amount of joint involvement differentiates rheumatoid arthritis into different clinical subsets
Rheumatoid arthritis (RA) is a heterogeneous disease with variable symptoms, prognosis, and treatment response, necessitating refined patient classification. We applied multimodal deep learning and clustering to identify distinct RA phenotypes using baseline clinical data from 1,387 patients in the Leiden Rheumatology clinic. Four Joint Involvement Patterns (JIP) emerged: foot-predominant arthritis, seropositive oligoarticular disease, seronegative hand arthritis, and polyarthritis. Findings were validated in clinical trial data (n = 307) and an independent secondary care cohort (n = 515). Clusters showed high stability and significant differences in remission rates (P = 0.007) and methotrexate failure (P < 0.001). JIP-hand patients had superior outcomes (particularly in ACPA-positive patients) versus JIP-foot (HR:0.37, P < 0.001) and JIP-poly (HR:0.33, P = 0.005), independent of baseline disease activity and clinical markers. Synovial histology analysis (n = 194) revealed distinct inflammatory patterns across clusters, hinting at different underlying biological mechanisms. These validated RA phenotypes based on joint involvement patterns may enable targeted research into disease mechanisms and personalized treatment strategies.
Authors
- Viviana Antonella Pacucci
- Marcel J. T. Reinders (ORCID: https://orcid.org/0000-0002-1148-1562)
- Maria Rita Gigante (ORCID: https://orcid.org/0000-0001-9509-1977)
- Stefano Alivernini (ORCID: https://orcid.org/0000-0002-7383-4212)
- Dario Bruno (ORCID: https://orcid.org/0000-0002-6647-9208)
- Rachel Knevel (ORCID: https://orcid.org/0000-0002-7494-3023)
- Lavinia Agra Coletto (ORCID: https://orcid.org/0000-0001-6613-9468)
- Erik B. van den Akker (ORCID: https://orcid.org/0000-0002-7693-0728)
- Clara Di Mario (ORCID: https://orcid.org/0000-0001-9459-3326)
- Annette H M van der Helm–van Mil (ORCID: https://orcid.org/0000-0001-8572-1437)
- Barbara Tolusso (ORCID: https://orcid.org/0000-0002-9108-6609)
- Simone Perniola (ORCID: https://orcid.org/0000-0001-6918-4731)
- T. Huizinga (ORCID: https://orcid.org/0000-0001-7033-7520)
- Luca Petricca (ORCID: https://orcid.org/0000-0003-3544-3162)
- M. Maurits (ORCID: https://orcid.org/0000-0002-3266-6232)
- Herman Kasper Glas (ORCID: https://orcid.org/0000-0003-0140-5934)
- Tjardo Daniël Maarseveen (ORCID: https://orcid.org/0000-0003-1701-1040)
- Bianca M. Boxma‐de Klerk (ORCID: https://orcid.org/0000-0003-0056-5872)
- Marco Gessi
- Sytske Anne Bergstra (ORCID: https://orcid.org/0000-0002-7136-5248)
- Stefan Böhringer (ORCID: https://orcid.org/0000-0001-9108-9212)
- Elisa Gremese (ORCID: https://orcid.org/0000-0002-2248-1058)
- Maria Antonietta D’Agostino (ORCID: https://orcid.org/0000-0002-5347-0060)
- N. Steinz (ORCID: https://orcid.org/0009-0009-4314-8228)
- Josien Veris-van Dieren
- Denise Campobasso
Institutions
- Università Cattolica del Sacro Cuore (IT)
- Leiden University Medical Center (NL)
- Erasmus MC (NL)
- Agostino Gemelli University Polyclinic (IT)
- GGD Zuid Limburg (NL)
- Newcastle University (GB)
- Delft University of Technology (NL)
Publication Details
- Journal
- npj Digital Medicine
- Published
- 2025-10-23
- DOI
- https://doi.org/10.1038/s41746-025-01997-1
- Citations
- 4
- Primary Topic
- Rheumatoid Arthritis Research and Therapies
- Type
- article
- Field-Weighted Citation Impact
- 6.67
Funders
- European Commission
- Universiteit Leiden
- ZonMw
- Leids Universitair Medisch Centrum