AB0881 Guselkumab Provides Sustained Improvements in Health-Related Quality of Life in Patients With Active Psoriatic Arthritis Through 2 Years of DISCOVER-2

Abstract

BackgroundPsoriatic arthritis (PsA), a chronic inflammatory disease characterized by peripheral arthritis, axial inflammation, dactylitis, enthesitis, and skin/nail psoriasis, is associated with reduced health-related quality of life (HRQoL).ObjectivesTo assess long-term effect of guselkumab (GUS), a human monoclonal antibody that selectively targets the interleukin (IL)-23p19 subunit, on HRQoL of bio-naïve PsA patients (pts) who participated in the Phase 3 2-year DISCOVER-2 trial.1MethodsPts with active PsA despite nonbiologic disease-modifying antirheumatic drugs (DMARDs) and/or nonsteroidal anti-inflammatory drugs (NSAIDs) received GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). At W24, PBO pts crossed over to GUS 100 mg Q4W. HRQoL was assessed using the pt-reported EuroQoL-5 Dimension-5 Level (EQ-5D-5L) questionnaire index and EuroQol Visual Analog Scale (EQ-VAS), widely used and complimentary tools that allow pts to provide a global assessment of their HRQoL. The EQ-5D-5L index assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression; an index score is derived ranging from 0 (death) to 1 (perfect health).2 EQ-VAS assesses pt health state on a scale of 0-100, with higher scores indicating better health. Using mixed effects models for repeated measures (MMRM), least squares (LS) mean changes from baseline in the EQ-5D-5L index and EQ-VAS through W100 were assessed. Observed changes from baseline were evaluated; in pts who met treatment failure rules before W24 and in pts who discontinued with missing data after W24, changes from baseline were imputed as 0.ResultsGUS-treated pts achieved greater improvements in pt-reported health status than PBO at both W16 and W24 when evaluated using both the EQ-5D-5L index score and the EQ-VAS. The improvements by GUS in EQ-5D-5L index scores through W24 (0.12 for GUS Q4W/Q8W vs 0.05 for PBO; each nominal p<0.0001) were maintained with continued GUS through 2 years (0.15 for GUS Q4W/Q8W) (Table 1). PBO-treated pts who started GUS at W24 reported comparable improvements in their HRQoL by W52 (0.12), with maintenance though W100 (0.14). Similar results were observed with EQ-VAS (Figure 1). W24 improvements in EQ-VAS scores were greater following GUS treatment (18.2/18.4 GUS Q4W/Q8W) vs PBO (6.8; nominal p<0.0001). EQ-VAS scores continued to improve with GUS through 2 years (25.0/24.6 GUS Q4W/Q8W). Likewise, PBO-treated pts who crossed over to GUS at W24 experienced improvements in HRQoL by W52 (18.8), with maintenance through W100 (21.2).Table 1.LS mean change from baseline through W100 in EQ-5D-5L indexGUS 100mg Q4W(W0-100)GUS 100mg Q8W(W0-100)PBO → GUS 100 mg Q4WPBO(W0-24)GUS(W24-100)Week162410016241001624100N243244243247246248244244244LS mean change (95% CI)0.10 (0.09,0.12)0.12 (0.1,0.13)0.15 (0.13,0.16)0.11 (0.1,0.13)0.12 (0.1,0.13)0.15 (0.13,0.17)0.06 (0.04,0.07)0.05 (0.04,0.07)0.14 (0.12,0.16) Diff vs. PBO0.04 (0.02,0.06)0.06 (0.04,0.09)--0.05 (0.03,0.07)0.06 (0.04,0.08)-------- Nominal p-value<0.0001<0.0001--<0.0001<0.0001--------CI=Confidence interval; Diff=DifferenceConclusionIn bio-naïve pts with active PsA receiving GUS, earlier improvements (at the first timepoint assessed) in self-reported HRQoL measures were sustained through 2 years.