POS1538 SAFETY OF GUSELKUMAB ACROSS DIVERSE PATIENT SUBGROUPS WITH PSORIATIC DISEASE: AN INTEGRATED ANALYSIS OF 11 PHASE 2/3 CLINICAL STUDIES IN PSORIASIS AND PSORIATIC ARTHRITIS

Abstract

BackgroundA higher prevalence of comorbidities, such as obesity, prior treatments, and certain demographics (e.g., age and sex) in patients (pts) with psoriatic disease (PsD) may lead to an increased risk of adverse events (AEs), sometimes serious[1]. Guselkumab (GUS), a fully human, selective IL-23p19-subunit inhibitor approved to treat (tx) adults with active psoriatic arthritis (PsA) and moderate to severe plaque psoriasis (PsO), has shown a favorable safety profile consistent between PsA and PsO pts through up to 2 and 5 years (yrs) of follow-up in the pooled PsA and PsO trials, respectively[2].ObjectivesAn integrated post hoc analysis evaluated GUS safety in subgroups of pts with PsD, stratified by baseline (BL) characteristics of interest, using pooled safety data from 11 Phase 2/3 trials of GUS, including four in PsA (Phase 2, DISCOVER-1, DISCOVER-2, COSMOS) and seven in PsO (X-PLORE, VOYAGE-1, VOYAGE-2, NAVIGATE, ORION, ECLIPSE, Japanese registration).MethodsGUS 100 mg subcutaneous (SC) was administered at Week (W) 0, W4, then every 4 W (Q4W) or Q8W in PsA trials and at W0, W4, then Q8W in PsO trials (additional doses were investigated in X-PLORE). Pts randomized to placebo (PBO) crossed over to GUS Q4W or Q8W at W24 in PsA trials and to GUS Q8W at W16 in 5 of the PsO trials. Pooled safety data were summarized for the PBO-controlled period (PsA: W0-24; PsO: W0-16) and through the end of the reporting period (PsA: up to 2 yrs; PsO: up to 5 yrs). Incidence rates of key safety events were adjusted for duration of follow-up and reported per 100 pt-yrs (PY), along with 95% CI. BL characteristics of interest in pts randomized to GUS or PBO (N=3318), were prior biologic use (26% yes; 74% no), age (94% <65; 6% ≥65 yrs), sex (62% male; 38% female), and BMI (26% under/normal weight; 34% overweight; 40% obese).ResultsDuring the PBO-controlled periods, 1061 pts received PBO (395 PY) and 2257 received GUS (856 PY). Through the end of the reporting periods, 4399 GUS-tx pts (PsA: 1508; PsO: 2891) contributed 10,787 PY of follow-up (PsA: 2125 PY; PsO: 8662 PY). BL characteristics were similar across 4 PsA trials and generally similar across 7 PsO trials. The PsO trials included more males and pts with extensive skin disease than the PsA trials. Distribution of PsD pts across BL subgroups generally provided sufficient sample size, although pts ≥65 yrs accounted for only 6% of all PsD pts. Throughout the PBO-controlled period, pooled incidence rates of overall AEs were generally similar between GUS- and PBO-tx pts and rates of serious AEs (SAEs), AEs leading to study agent discontinuation, infections, and serious infections were low and comparable between GUS- and PBO-tx pts, regardless of the BL characteristics assessed. The rates of safety events evaluated were stable or reduced through the end of the reporting period for GUS-tx pts within each BL subgroup (Figure 1).ConclusionThis comprehensive integrated analysis of GUS safety demonstrated a favorable safety profile across a broad population of pts irrespective of the BL characteristics assessed. Overall, safety event rates in GUS-tx pts were comparable to or lower than PBO during short-term follow-up. Rates of SAEs and serious infections remained low and stable through long-term follow-up.