{
  "abstract": "Objectives To identify in a genetically susceptible population individuals at higher risk of developing rheumatoid arthritis (RA) using a classification approach combining known epidemiological risk factors, serological biomarkers, genetics, clinical signs and symptoms.Methods We used data from the prospective SCREEN-RA (Evaluation of a SCREENing strategy for Rheumatoid Arthritis) cohort of 1540 first-degree relatives of RA patients (RA-FDRs). The primary outcome was the development of RA. Additionally, we used seropositive inflammatory arthritis (IA) as a secondary outcome for exploratory analyses. Balanced random forest (BRF) models were fit and evaluated through fivefold cross-validation to avoid overfitting. We chose a classification threshold that targeted high sensitivity.Results After a mean follow-up of 7.1 years, 27 participants developed RA and 126 developed seropositive IA. The BRF demonstrated moderate predictive performance, characterised by high sensitivity (≥0.85) but modest specificity. Rheumatoid factors (RFs) had the highest importance in RA prediction, followed by symptoms of ‘clinically suspected arthralgia’ (CSA) scale. Age, gender and anti-RA33 autoantibodies were the main variables for the prediction of seropositive IA.Conclusions Overall, the results demonstrate that predicting RA by combining genetics, serological biomarkers, epidemiological risk factors and clinical signs is promising, although model generalisation remains challenging. The low prevalence of RA in the cohort complicates the development of highly accurate prediction models. Future efforts should focus on including external validation and potentially incorporating additional biomarkers to enhance the sensitivity and overall performance of the predictive tests.",
  "authors": [
    {
      "affiliations": [
        "Division of Rheumatology, Geneva University Hospitals, Geneve, Switzerland"
      ],
      "name": "Romain Aymon"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Geneva University Hospitals, Geneve, Switzerland"
      ],
      "name": "Céline Lamacchia"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Geneva University Hospitals, Geneve, Switzerland"
      ],
      "name": "Benoit Thomas P Gilbert"
    },
    {
      "affiliations": [
        "Thermo Fisher Scientific, Freiburg, Germany"
      ],
      "name": "Maresa Grundhuber"
    },
    {
      "affiliations": [
        "Thermo Fisher Scientific, Freiburg, Germany"
      ],
      "name": "Isabel Gehring"
    },
    {
      "affiliations": [
        "Thermo Fisher Scientific, Freiburg, Germany"
      ],
      "name": "Sascha Swiniarski"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Geneva University Hospitals, Geneve, Switzerland"
      ],
      "name": "Olivia Studer"
    },
    {
      "affiliations": [
        "Université de Montpellier, Montpellier, France",
        "Physiology and Experimental Medicine of Heart and Muscles, Montpellier, France"
      ],
      "name": "Zubeyir Salis"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Geneva University Hospitals, Geneve, Switzerland"
      ],
      "name": "Romain Guemara"
    },
    {
      "affiliations": [
        "Department of Immunology and Allergy, Geneva University Hospitals, Geneve, Switzerland"
      ],
      "name": "David Spoerl"
    },
    {
      "affiliations": [
        "Department of Rheumatology, HFR, Fribourg, Switzerland"
      ],
      "name": "Jean Dudler"
    },
    {
      "affiliations": [
        "Rheumatology and Immunology, Inselspital Universitatsspital Bern, Bern, BE, Switzerland"
      ],
      "name": "Burkhard Möller"
    },
    {
      "affiliations": [
        "Rheumatology, Lausanne University Hospital, Lausanne, Switzerland",
        "Faculty of Medicine, University of Lausanne, Lausanne, Switzerland"
      ],
      "name": "Diana Dan"
    },
    {
      "affiliations": [
        "Rheumatology, Réseau hospitalier neuchâtelois, La Chaux-de-Fonds, Switzerland"
      ],
      "name": "Laure Brulhart"
    },
    {
      "affiliations": [
        "Rheumatology Office, Rheuma-Basel, Basel, Switzerland"
      ],
      "name": "Ines Von Mühlenen"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital Basel, Basel, Switzerland",
        "Department of Biomedicine, University of Basel, Basel, BS, Switzerland"
      ],
      "name": "Diego Kyburz"
    },
    {
      "affiliations": [
        "Division of Rheumatology and Immunology, Kantonsspital St Gallen, Sankt Gallen, SG, Switzerland"
      ],
      "name": "Andrea Rubbert-Roth"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University of Zurich, University Hospital Zurich, Zurich, Switzerland"
      ],
      "name": "Adrian Ciurea"
    },
    {
      "affiliations": [
        "Rheumazentrum Ostschweiz, St. Gallen, Switzerland"
      ],
      "name": "Ruediger Mueller"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Geneva University Hospitals, Geneve, Switzerland"
      ],
      "name": "Delphine S Courvoisier"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Geneva University Hospitals, Geneve, Switzerland",
        "Geneva Centre for Inflammation Research, Geneva University Hospitals, Geneve, Switzerland"
      ],
      "name": "Axel Finckh"
    }
  ],
  "title": "Identification of individuals at high risk of developing rheumatoid arthritis: a balanced random forest model in a cohort of 1544 first-degree relatives",
  "uid": "fb7a1145-17d8-5543-b80d-ed3e0c5ad313"
}