Document resource
Objectives Moderate BILAG-2004 flare definitions are less well validated than severe flare definitions, and moderate flares are reported less frequently in clinical trials. Moderate flares may be underestimated due to their measurement over a single interval when they may evolve over multiple intervals. We explore alternative definitions to estimate flare frequency, using data from the phase 3 PHOENYCS GO trial ( NCT04294667) of dapirolizumab pegol (DZP).DZP, a novel CD40L inhibitor, consists of a polyethylene glycol (PEG)-conjugated antigen-binding fragment (Fab’) lacking an Fc domain. In PHOENYCS GO, the primary endpoint, BICLA response at Week 48, was met. Lower proportions of patients receiving DZP plus standard of care (DZP+SOC) versus placebo (PBO)+SOC had severe BILAG-2004 flares through Week 48 (11.6% versus 23.4%; nominal p=0.0257).Methods In PHOENYCS GO, 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. Pre-specified severe BILAG-2004 flares were defined as >=1 BILAG-2004 Grade A due to a new/worse individual item(s). Moderate BILAG-2004 flares were defined by a pre-specified definition and two alternative post hoc definitions ( figure 1A). Achievement and maintenance of glucocorticoid doses <=7.5/<=5 mg/day while remaining flare-free was assessed.Results At Week 48, higher proportions of patients receiving PBO+SOC had moderate and moderate/severe BILAG-2004 flares using the alternative definitions; lower proportions of patients receiving DZP+SOC versus PBO+SOC had flares by all definitions ( figure 1B–1C). Time to moderate/severe BILAG-2004 flares through Week 48 was longer for patients receiving DZP+SOC versus PBO+SOC by all definitions. Greater proportions of patients receiving DZP+SOC versus PBO+SOC achieved glucocorticoid doses <=7.5/<=5 mg/day from Week 24 through Week 48 and remained flare-free by all definitions (figure 1D–1E).Abstract S15:02 Figure 1Moderate and moderate/severe BILAG-2004 flare outcomes by pre-specified and alternative definitionsConclusions Alternative definitions of moderate BILAG-2004 flares, considering symptoms across consecutive visits, led to greater identification of flares in patients receiving PBO+SOC. Patients receiving DZP+SOC versus PBO+SOC had fewer BILAG-2004 flares by all definitions, and more frequently tapered glucocorticoid dose while remaining flare-free. These results support the re-evaluation of how flares are captured in clinical trials; the alternative definitions may better reflect clinical practice.