POS1044 GUSELKUMAB PROVIDES CONSISTENT AND DURABLE PAIN IMPROVEMENT IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: RESULTS OF 2 PHASE 3, RANDOMIZED, CONTROLLED CLINICAL TRIALS

Abstract

Background/Purpose: Guselkumab (GUS), an IL-23p19- subunit inhibitor, demonstrated significant efficacy vs placebo (PBO) in achieving ACR20 response at week (W)24 in patients with active PsA in DISCOVER-1& 2 trials.1,2 PsA patients reported pain relief as a treatment priority.3 These post-hoc analyses further assessed GUS effect on patient-reported pain across outcome measures and maintenance of pain relief with up to 2 years of GUS. Methods: Patients with active PsA despite standard therapies in DISCOVER-1 (1-year; n = 381; 31% of patients received 1-2 prior TNF inhibitors) and DISCOVER-2 (2-years; n = 739; biologic-naïve) were randomized (1:1:1) to GUS 100mg every-4- weeks (Q4W); GUS 100mg at W0, W4, then Q8W; or PBO with crossover to GUS 100mg Q4W at W24 (PBO→Q4W). Patients rated pain using a 0-10 VAS (Patient Pain) as part of ACR/Disease Activity in PsA/Minimal Disease Activity response criteria and reported Bodily Pain intensity over the past 4 W via the 36-Item Short-Form Health Survey question 21 (0-5). Patients with spondylitis and peripheral arthritis at baseline rated their Spinal and Joint Pain (0-10) as part of BASDAI. Percent improvement from baseline in tender (TJC; 0-68) and swollen (SJC; 0-66) joint counts (determined by independent assessors) was determined to evaluate consistency of improvements in patient-reported vs physician-derived pain measures. Results: In DISCOVER-2, mean baseline Bodily Pain (range: 4.4-4.5)/ Patient Pain (6.2-6.3)/ Spinal Pain (6.5-6.7)/ Joint Pain (6.3-6.8)/ SJC (11.7-12.9)/ TJC (19.8-22.4) indicated moderate pain and disease activity at study outset. GUS-treated patients reported ∼2x the improvement in Patient Pain/Spinal Pain/Joint Pain/Bodily Pain intensity at W24 vs PBO; GUS improvements were maintained or further increased at W52/W100. PBO→Q4W patients had similar improvements in pain as GUS-randomized patients (Table, Figure). Patient-reported pain appeared more sensitive to treatment effect, with larger differences in percent improvement vs PBO, than physician-reported TJC/SJC at W24 (Figure); further research is warranted. While patterns were consistent, pain improved to a lesser degree than TJC/SJC, suggesting other causative factors. Consistent results were seen in DISCOVER-1 through 1 year (data not shown). Among 748 GUS-treated patients across DISCOVER-1& 2, substantial proportions achieved meaningful improvement in Patient Pain at early time points: 32% (W4) and 48% (W8) achieved ≥20% improvement; 28% (W12) and 33% (W16) achieved ≥50% improvement. At W24, 63% and 39% reported ≥20% and ≥50% pain improvement. Conclusions: GUS provided consistent and durable improvements in patient-reported pain across several measures. Patient-reported pain as an early and sensitive indicator of treatment effect in patients with active PsA and additional factors underlying pain merit further evaluation. (Table Presented).