PO:05:136 Measurement of kidney disease in a novel treatment response measure for systemic lupus erythematosus clinical trials

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Objectives To define a fit-for-purpose clinical outcome assessment and thresholds for entry and improvement for nephropathy in a novel multi-domain outcome measure for Systemic Lupus Erythematosus (SLE) clinical trials, the Treatment Response Measure for Systemic Lupus Erythematosus (TRM-SLE).Methods An international working group comprising eight adult and paediatric clinicians (rheumatologists and nephrologists) and four patient/patient organisation representatives, primarily with lived experience of lupus nephritis, completed a multi-step consensus process. First, the scope of a nephropathy domain was defined. Candidate response measures were then nominated, shortlisted, and evaluated via a systematic literature review (SLR) guided by COSMIN and OMERACT guidelines. Informed by the SLR, the working group used nominal group technique (NGT) to reach consensus on a response measure, as well as entry, minimum and complete response thresholds.Results The domain was defined with 100% consensus as ‘active kidney disease attributed to lupus that impacts the patient and is modifiable by therapy to reduce or control disease’, with domain scope including glomerular disease (including podocytopathy), tubulo-interstitial nephritis and renal vasculopathy. From 61 nominated measures, of which 30 were unique, four measures to fit this scope were shortlisted for the SLR, which screened 8,012 articles and identified 50 relevant papers for review. Consensus was reached to measure renal response using proteinuria improvement, accompanied by no significant worsening of renal function based on estimated glomerular filtration rate (eGFR, <20% of the baseline value). The preferred method for proteinuria assessment was urine protein-creatinine ratio (UPCR) based on a 24-hour or first morning void collection; and to calculate eGFR using a validated equation. Thresholds were defined for entry (UPCR >1g/g), minimum clinically-meaningful response (UPCR improvement >50% from baseline and UPCR <1g/g if sub-nephrotic at baseline, or <3g/g if nephrotic at baseline) and complete response (UPCR ≤0.2g/g) ( figure 1).Abstract PO:05:136 Figure 1Conclusions For the nephropathy domain of the multi-domain TRM-SLE instrument for measuring treatment response in general SLE trials, consensus was achieved to use proteinuria improvement without significant eGFR worsening as the outcome measure, and clinically meaningful thresholds for entry and improvement were defined. This outcome measure will allow assessment of patients with active kidney disease in general SLE trials.

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