{
  "abstract": "While targeted therapies have reshaped the clinical management of immune-mediated inflammatory diseases (IMIDs), primary non-response remains a major obstacle for many patients. Combining two targeted therapies is an emerging strategy to overcome this therapeutic ceiling, but the number of possible drug pairs makes prioritization difficult. For this objective, we present mitigation of non-response signature (MNRS), a computational approach that uses longitudinal blood transcriptomic data from six IMIDs treated with different targeted therapies to identify the most promising drug combinations. The approach identifies complementary pairs of biologic agents and small molecules, as well as potentially incompatible pairs. In rheumatoid arthritis, anti-TNF and anti-interleukin 6 receptor therapy emerges as highly complementary; single-cell analysis localizes this effect to CD14+ monocytes, and a collagen-induced arthritis mouse model confirms that the combination outperforms monotherapy. These findings show that longitudinal patient data help prioritize drug combinations for clinical testing across immune-mediated diseases.",
  "abstract_shown": true,
  "affiliations": [
    "IMIDomics, Inc., Barcelona, Spain",
    "Universitat de Barcelona (UB), Barcelona, Spain",
    "Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain",
    "Hospital Universitari Vall d'Hebron, Department of Rheumatology, Barcelona, Spain",
    "Laboratory of Experimental Immunology, Istituto Dermopatico dell′Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy",
    "Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain",
    "HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA",
    "Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain",
    "Fundació Clínic per a la Recerca Biomèdica, Department of Rheumatology, Barcelona, Spain",
    "Hospital Universitari Germans Trias i Pujol, Department of Dermatology, Badalona, Spain",
    "Hospital Universitari Germans Trias i Pujol, Department of Gastroenterology, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Badalona, Spain",
    "Hospital Universitario de La Princesa, Department of Gastroenterology, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain",
    "Hospital General Universitario de Guadalajara, Department of Rheumatology, Guadalajara, Spain",
    "Charité-Universitätsmedizin Berlin, Department of Gastroenterology, Berlin, Germany",
    "Department of Medicine, Section of Dermatology, University of Verona, Verona, Italy",
    "CREATE Centre, Section of Rheumatology, Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK",
    "ICREA, Barcelona, Spain",
    "Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 26,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sergio H. Martínez-Mateu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yolanda Guillén"
    },
    {
      "affs": [
        2
      ],
      "name": "Edgar Angelats"
    },
    {
      "affs": [
        3
      ],
      "name": "María A. López-Lasanta"
    },
    {
      "affs": [
        4
      ],
      "name": "Stefania Madonna"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Laura Jiménez-Gracia"
    },
    {
      "affs": [
        6
      ],
      "name": "Ivan Rodriguez-Nunez"
    },
    {
      "affs": [
        0
      ],
      "name": "Damiana Álvarez-Errico"
    },
    {
      "affs": [
        7
      ],
      "name": "Adrià Aterido"
    },
    {
      "affs": [
        7
      ],
      "name": "Raül Tortosa"
    },
    {
      "affs": [
        5
      ],
      "name": "Max Ruiz"
    },
    {
      "affs": [
        2
      ],
      "name": "Pau Serra"
    },
    {
      "affs": [
        2,
        8
      ],
      "name": "Juan D. Cañete"
    },
    {
      "affs": [
        9
      ],
      "name": "Jose M. Carrascosa"
    },
    {
      "affs": [
        10
      ],
      "name": "Eugeni Domènech"
    },
    {
      "affs": [
        11
      ],
      "name": "Javier P. Gisbert"
    },
    {
      "affs": [
        12
      ],
      "name": "Jesús Tornero"
    },
    {
      "name": "IMID-Consortium"
    },
    {
      "affs": [
        13
      ],
      "name": "Britta Siegmund"
    },
    {
      "affs": [
        14
      ],
      "name": "Giampiero Girolomoni"
    },
    {
      "affs": [
        15
      ],
      "name": "Ernest H.S. Choy"
    },
    {
      "affs": [
        6
      ],
      "name": "Richard M. Myers"
    },
    {
      "affs": [
        1,
        5,
        16
      ],
      "name": "Holger Heyn"
    },
    {
      "affs": [
        2,
        17
      ],
      "name": "Pere Santamaria"
    },
    {
      "affs": [
        3,
        7
      ],
      "name": "Sara Marsal"
    },
    {
      "affs": [
        7
      ],
      "name": "Antonio Julià"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/45kdsp20vnw42.bib",
  "cited_by": 0,
  "doi": "10.1016/j.xcrm.2026.103026",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710146/",
  "id": "45kdsp20vnw42",
  "issns": [
    "2666-3791"
  ],
  "landing_url": "https://doi.org/10.1016/j.xcrm.2026.103026",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "2745|Rheumatoid Arthritis Research and Therapies"
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  "openalex": "W7212230907",
  "pdf_url": "https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(26)00443-X.pdf",
  "pmcid": "PMC13710146",
  "pmid": "42727586",
  "published": "2026-09-11",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/45kdsp20vnw42.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:10Z",
      "native_id": "PMC13710146",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.xcrm.2026.103026"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Rheumatoid Arthritis Research and Therapies",
      "subfield": "general"
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  ],
  "title": "Uncovering combination therapies for immune-mediated inflammatory diseases through systems biology analysis on longitudinal patient data",
  "title_text": "Uncovering combination therapies for immune-mediated inflammatory diseases through systems biology analysis on longitudinal patient data",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:10Z",
  "url": "https://research.draconitic.com/paper/45kdsp20vnw42",
  "venue": "Cell Reports Medicine",
  "versions": []
}