{
  "abstract": "Objective: Dual targeting of type I interferon and B-cell pathways could be a promising strategy for SLE. We examined biomarker and gene expression changes over 24 weeks in patients treated with upadacitinib, a Janus kinase (JAK) inhibitor that modulates interferon signalling, alone or in combination with elsubrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor that targets B-cell pathways.\n\nMethods: SLEek (NCT03978520), a phase 2, randomised, double-blind, placebo-controlled study, enrolled adults with moderately to severely active SLE. This analysis includes patients who received upadacitinib 30 mg (n=62), ABBV-599 (upadacitinib 30 mg plus elsubrutinib 60 mg; n=68) or placebo (n=75). Whole blood was collected at baseline (week 0) and various time points over 24 weeks to analyse serum immunoglobulins, immune cell counts and proteomic profiles. Weighted gene coexpression network analyses evaluated differentially expressed genes.\n\nResults: Both upadacitinib and ABBV-599 significantly reduced and sustained lower anti-double-stranded DNA autoantibody levels compared with baseline through week 24, whereas upadacitinib monotherapy alone reduced plasma cell percentages. Proteomic analysis found modulation of 301 proteins, including reductions in interferon-related and B-cell-associated proteins. RNA sequencing revealed significant changes in interferon, plasma cells and cell cycle gene modules correlating with clinical biomarkers.\n\nConclusions: Upadacitinib was associated with a reduction in both autoantibody and B-cell activation and with key gene expression changes in SLE pathogenic pathways. Dual JAK/BTK inhibition did not provide additional impact on most immunological parameters. These findings support JAK inhibition as a targeted monotherapy for SLE.\n\nTrial registration number: NCT03978520.",
  "abstract_shown": true,
  "affiliations": [
    "Precision Medicine Immunology, AbbVie Inc, Chicago, Illinois, USA",
    "Quantitative Medicine and Genomics, AbbVie Inc, Chicago, Illinois, USA",
    "Data and Statistical Sciences, AbbVie Inc, Chicago, Illinois, USA",
    "Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Marie-Claude Gaudreau"
    },
    {
      "affs": [
        0
      ],
      "name": "Michelle Catalina"
    },
    {
      "affs": [
        0
      ],
      "name": "Thierry Sornasse"
    },
    {
      "affs": [
        1
      ],
      "name": "Archana Iyer"
    },
    {
      "affs": [
        1
      ],
      "name": "Ioan Filip"
    },
    {
      "affs": [
        0
      ],
      "name": "Shalina Contrepois"
    },
    {
      "affs": [
        2
      ],
      "name": "James Fann"
    },
    {
      "affs": [
        3
      ],
      "name": "Joan T Merrill"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4mmcebj7fbp7x.bib",
  "cited_by": 0,
  "doi": "10.1136/lupus-2026-002162",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723914/",
  "id": "4mmcebj7fbp7x",
  "issns": [
    "2053-8790"
  ],
  "landing_url": "https://doi.org/10.1136/lupus-2026-002162",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "1506"
    ],
    [
      "heading",
      "2253"
    ],
    [
      "heading",
      "Biomarker Studies"
    ],
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2745|Systemic Lupus Erythematosus Research"
    ]
  ],
  "openalex": "W7224225028",
  "pdf_url": "https://lupus.bmj.com/content/13/2/e002162.full.pdf",
  "pmcid": "PMC13723914",
  "pmid": "42957324",
  "published": "2026-10-29",
  "publisher": "BMJ Publishing Group",
  "ris": "https://research.draconitic.com/paper/4mmcebj7fbp7x.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:22:28Z",
      "native_id": "PMC13723914",
      "source": "pmc",
      "url": "https://doi.org/10.1136/lupus-2026-002162"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Systemic Lupus Erythematosus Research",
      "subfield": "general"
    }
  ],
  "title": "Effect of upadacitinib and ABBV-599 on biomarkers in SLE: results from the phase 2 SLEek study",
  "title_text": "Effect of upadacitinib and ABBV-599 on biomarkers in SLE: results from the phase 2 SLEek study",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:39Z",
  "url": "https://research.draconitic.com/paper/4mmcebj7fbp7x",
  "venue": "Lupus Science & Medicine",
  "versions": []
}