{
  "abstract": "Objectives To design a trial to evaluate whether belimumab administered 4-8 weeks after rituximab improves clinical response in systemic lupus erythematosus (SLE) patients with high baseline serum IgA2 anti-dsDNA antibodies, compared with rituximab alone. This biomarker-enrichment trial was developed from the identification of serum IgA2 anti-dsDNA antibodies as a predictive biomarker of response to belimumab after rituximab based on the BEAT-lupus and CALIBRATE trials.Methods STRATIFY lupus is a multicentre, double-blind, randomised, placebo-controlled Phase IIIa trial. 66 participants with active SLE refractory to conventional therapy and serum IgA2 anti-dsDNA > 12.5 AU will be enrolled from May 2026. All participants will receive rituximab followed 4-8 weeks later by iv belimumab or placebo for 48 weeks. The primary endpoint is a modified Major Clinical Response (mMCR) at 52 weeks, defined by improvement in BILAG-2004 and modified SLEDAI-2K indices and glucocorticoid tapering to < or =7.5 mg/day. Key secondary outcomes include time to flare, quality-of-life scores, and infection rates.Trial DiagramResults Analysis of 3 independent cohorts indicates that 40-50% of lupus patients whose disease is refractory to conventional therapy are positive for this biomarker. The target sample size for the trial (n=66) provides 90% power to detect a clinically meaningful difference in mMCR between groups assuming a 51% vs 9% response based on observed differences in the BEAT-LUPUS trial (sample size adjusted by 20% for attrition).Binary outcomes will be compared using exact risk differences, time-to-event outcomes by Kaplan–Meier curves and stratified log-rank tests, and continuous outcomes by mixed-effects regression.This biomarker-enrichment design markedly reduces the required sample size to demonstrate efficacy. If unselected patients were randomised (‘non-enriched’ design), >700 participants would be required (delta = 14% between trial arms for all participants, combined data from BEAT-lupus and CALIBRATE trials), underscoring the efficiency and precision of the biomarker enrichment strategy.Abstract PO:08:220 Figure 1Conclusions STRATIFY lupus is the first biomarker-enrichment trial in SLE designed to prospectively test a validated molecular predictor of response to combination B-cell targeted therapy. Positive results would establish IgA2 anti-dsDNA as a clinically actionable biomarker, measurable by routine ELISA, supporting precision stratification and improved access to advanced therapies in lupus.",
  "authors": [
    {
      "affiliations": [
        "Department of Rheumatology, University College London, London, UK"
      ],
      "name": "Michael Ehrenstein"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University of Birmingham, Birmingham, UK"
      ],
      "name": "Caroline Gordon"
    },
    {
      "affiliations": [
        "Comprehensive Clinical Trial Unit, University College London, London, UK"
      ],
      "name": "Kashfia Chowdhury"
    },
    {
      "affiliations": [
        "Comprehensive Clinical Trial Unit, University College London, London, UK"
      ],
      "name": "Olivia Mahoro"
    },
    {
      "affiliations": [
        "Comprehensive Clinical Trial Unit, University College London, London, UK"
      ],
      "name": "Lee Webber"
    },
    {
      "affiliations": [
        "Comprehensive Clinical Trial Unit, University College London, London, UK"
      ],
      "name": "Felicia Ikeji"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University College London, London, UK"
      ],
      "name": "Claire Beesley"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust, Doncaster, UK"
      ],
      "name": "Chee-Seng Yee"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University of Manchester, Manchester, UK"
      ],
      "name": "Ben Parker"
    },
    {
      "affiliations": [
        "Department of Biostatistics, University of Newcastle, Newcastle, UK"
      ],
      "name": "James Wason"
    },
    {
      "affiliations": [
        "Comprehensive Clinical Trial Unit, University College London, London, UK"
      ],
      "name": "Nick Freemantle"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University College London, London, UK"
      ],
      "name": "Eleanor Hawkins"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University College London, London, UK"
      ],
      "name": "Muhammad Shipa"
    }
  ],
  "title": "PO:08:220 STRATIFY lupus: a phase IIIa randomised placebo-controlled biomarker-enrichment trial of belimumab after rituximab in systemic lupus erythematosus",
  "uid": "aeec22f4-9f03-576e-a015-9dcea4ba783c"
}