{
  "abstract": "Objectives Current first-line treatment of SLE is antimalarials, conventional immunosuppressants (cIS) and glucocorticoids (GC) with biologics usually reserved for refractory disease. However, GC exposure, damage accrual and mortality are highest within the first year of SLE. Predictors of severe SLE and early use of biologics are also predictors of good response to rituximab. Deferring biologic use may therefore be inefficient and miss the opportunity to prevent severe disease. FIRST will evaluate the clinical and cost-effectiveness of adding rituximab to cIS and GC at the onset of moderate-to-severe SLE compared with placeboMethods FIRST is a multicentre, double-blind, randomised, placebo-controlled study in the UK. Key inclusion criteria are age >=5 years; within 12 months of SLE diagnosis; within 4 weeks of starting a first cIS at screening; and moderate-to-severe activity based on Easy-BILAG. 128 participants will be randomised 1:1 to rituximab or placebo, in addition to standard therapy such as cIS, hydroxychloroquine and GC. Infusions will be given on days 1 and 15 at months 0 and 6, each preceded by intravenous methylprednisolone in both arms. Outcome measures include LLDAS, DORIS, Easy-BILAG, cumulative GC dose, EQ-5D, SF-36, resource use and adverse events over 12 monthsResults The primary objective is to assess whether greater cumulative time in LLDAS over 12 months is achieved in the rituximab group compared with placebo. We will also evaluate secondary outcomes including cumulative time in DORIS remission, BILAG flares, GC exposure, SLICC damage index, HRQoL, healthcare costs and safetyConclusions FIRST will be the first trial of its kind to incorporate: (1) a biologic as first-line immunosuppressive in early SLE; (2) a time-on-target instead of response endpoint, capturing improvement, flare prevention, new organ involvement, GC exposure and cIS changes in a single outcome; (3) a whole life course population (4) a pragmatic design allowing changes in GC and cIS. We hypothesise that FIRST will include a broader spectrum of SLE presentations and first-line rituximab will reduce long-term damage accrual, cumulative GC exposure and the need for rescue therapies. Early optimisation of SLE management and effective disease control may also lead to greater patient satisfaction and improved quality of life outcomes.",
  "authors": [
    {
      "affiliations": [
        "Leeds Teaching Hospital NHS Trust, Leeds, UK"
      ],
      "name": "Rusyai Zalynda Ramli"
    },
    {
      "affiliations": [
        "Department of Health Sciences, University of York, York, UK"
      ],
      "name": "Puvan Tharmanathan"
    },
    {
      "affiliations": [
        "Department of Health Sciences, University of York, York, UK"
      ],
      "name": "Liz Cook"
    },
    {
      "affiliations": [
        "Department of Health Sciences, University of York, York, UK"
      ],
      "name": "Charlie Welch"
    },
    {
      "affiliations": [
        "Department of Health Sciences, University of York, York, UK"
      ],
      "name": "Andrew Mott"
    },
    {
      "affiliations": [
        "Department of Health Sciences, University of York, York, UK"
      ],
      "name": "Grace O Carroll"
    },
    {
      "affiliations": [
        "Department of Health Sciences, University of York, York, UK"
      ],
      "name": "Harriet Pyrah"
    },
    {
      "affiliations": [
        "Department of Health Sciences, University of York, York, UK"
      ],
      "name": "Gemma Hughes"
    },
    {
      "affiliations": [
        "Department of Health Sciences, University of York, York, UK"
      ],
      "name": "Yezy Ye"
    },
    {
      "affiliations": [
        "Department of Health Sciences, University of York, York, UK"
      ],
      "name": "Qian Zhao"
    },
    {
      "affiliations": [
        "Department of Health Sciences, University of York, York, UK"
      ],
      "name": "Alex Mitchell"
    },
    {
      "affiliations": [
        "Department of Health Sciences, University of York, York, UK"
      ],
      "name": "Steve Parrott"
    },
    {
      "affiliations": [
        "Department of Health Sciences, University of York, York, UK"
      ],
      "name": "Catherine Hewitt"
    },
    {
      "affiliations": [
        "Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK"
      ],
      "name": "Elena Moraitis"
    },
    {
      "affiliations": [
        "University College London, London, UK"
      ],
      "name": "Michael Ehrenstein"
    },
    {
      "affiliations": [
        "Department of Medicine, University of Cambridge, Cambridge, UK"
      ],
      "name": "David Jayne"
    },
    {
      "affiliations": [
        "Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, UK"
      ],
      "name": "Ian Bruce"
    },
    {
      "affiliations": [
        "Department of Paediatric Rheumatology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK"
      ],
      "name": "Olivia Lloyd"
    },
    {
      "affiliations": [
        "Patient’s representative, Cardiff, UK"
      ],
      "name": "Dalila Tremarias"
    },
    {
      "affiliations": [
        "School of Infection and Immunity, University of Glasgow, Glasgow, UK"
      ],
      "name": "Eve MD Smith"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, NIHR Leeds Biomedical Research Centre, Leeds, UK"
      ],
      "name": "Md Yuzaiful Md Yusof"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, NIHR Leeds Biomedical Research Centre, Leeds, UK"
      ],
      "name": "Edward M Vital"
    }
  ],
  "title": "PO:11:284 Design of the first-line rituximab in systemic lupus erythematosus trial (FIRST)",
  "uid": "9d60de5b-a57b-5cc5-811d-0f68b5f92e15"
}