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Objectives SLE causes diminished health-related quality of life (HRQoL) and significant patient burden. Despite existing treatments, patients may continue to experience symptoms including fatigue, musculoskeletal pain and morning stiffness. Dapirolizumab pegol (DZP) is a novel CD40L inhibitor with broad modulatory effects on SLE immunopathology; it consists of a polyethylene glycol (PEG)-conjugated antigen-binding fragment (Fab’), which lacks an Fc domain. In the phase 3 PHOENYCS GO trial ( NCT04294667), the primary endpoint was met; DZP plus standard of care (DZP+SOC) resulted in a significantly higher rate of BICLA response versus placebo (PBO)+SOC at Week 48 (49.5% versus 34.6%; p=0.0110). Here, we report patient-reported fatigue, musculoskeletal pain, morning stiffness and HRQoL outcomes from PHOENYCS GO.Methods In the 48-week PHOENYCS GO trial, patients were randomised 2:1 to intravenous DZP 24 mg/kg+SOC or PBO+SOC every 4 weeks. Investigators were required to taper glucocorticoid dose, starting by Week 8, for patients with baseline dose >7.5 mg/day prednisone equivalent.Patient-reported outcomes were assessed using the following measures: Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, FATIGUE-PRO (a novel SLE-specific measure covering three domains: Physical Fatigue, Mental and Cognitive Fatigue, and Susceptibility to Fatigue), pain and stiffness visual analogue scales of the Lupus Arthritis and Musculoskeletal Disease Activity (LAMDA) instrument, and LupusQoL.Results Baseline characteristics were comparable between groups (DZP+SOC: n=208; PBO+SOC: n=107); patients had substantial disease burden ( table 1). Patients receiving DZP+SOC versus PBO+SOC demonstrated consistently larger improvements to Week 48 in FACIT-Fatigue and FATIGUE-PRO scores (nominal p<0.05; figure 1A). A greater proportion of patients receiving DZP+SOC versus PBO+SOC achieved an improvement of >=4 points (minimal clinically important difference) in FACIT-Fatigue from baseline to Week 48 (50.5% versus 35.5%; nominal p=0.0131). Improvements at Week 48 in musculoskeletal pain and morning stiffness were also greater for patients receiving DZP+SOC versus PBO+SOC (nominal p<0.05; figure 1B). Patients receiving DZP+SOC demonstrated greater improvements to Week 48 in LupusQoL scores versus PBO+SOC (figure 1C).Abstarct PO:13:336 Figure 1LS mean change from baseline in fatigue, musculoskeletal pain, morning stiffness and LupusQoL scoresAbstarct PO:13:336 Table 1Baseline demographics and disease characteristicsConclusions In patients with SLE, DZP+SOC treatment was associated with benefits in fatigue, musculoskeletal pain, morning stiffness and HRQoL. Alongside previously reported improvements in clinical measures of SLE disease activity, these data suggest that DZP improves core patient-reported outcomes in SLE.