Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: pooled results through week 52 of two phase III, randomised, placebo-controlled studies

Abstract

ObjectivesTo evaluate the efficacy through 52 weeks of guselkumab, an interleukin 23-p19 subunit inhibitor, in subgroups of pooled psoriatic arthritis (PsA) patients from the DISCOVER-1 and DISCOVER-2 trials defined by baseline patient characteristics.MethodsAdults with active PsA despite standard therapies were enrolled in DISCOVER-1 (≥3 swollen and ≥3 tender joints, C reactive protein (CRP) level ≥0.3 mg/dL) and DISCOVER-2 (≥5 swollen and ≥5 tender joints, CRP ≥0.6 mg/dL, biological-naïve). Randomised patients received 100 mg guselkumab at weeks 0, 4, and then every 4 or 8 weeks (Q4W/Q8W) or placebo. Guselkumab effects on joint (ACR20/50/70), skin (IGA 0/1, IGA 0), patient-reported outcome (Health Assessment Questionnaire Disability Index/Functional Assessment of Chronic Illness Therapy-Fatigue) and disease severity (minimal disease activity/PsA Disease Activity Score low disease activity) endpoints were evaluated by patient sex, body mass index, PsA duration, swollen/tender joint counts, CRP level, percent body surface area with psoriasis, Psoriasis Area and Severity Index score, and conventional synthetic disease-modifying antirheumatic drug use at baseline.ResultsBaseline patients characteristics in DISCOVER-1 (N=381) and DISCOVER-2 (N=739) were well balanced across randomised groups. At week 24, 62% (232/373) and 60% (225/375), respectively, of guselkumab Q4W-treated and Q8W-treated patients pooled across DISCOVER-1 and DISCOVER-2 achieved the primary endpoint of ACR20 response versus 29% (109/372) of placebo-treated patients. Guselkumab treatment effect at week 24 was observed across patient subgroups. Within each patient subgroup, response rates across all disease domains were sustained or increased at week 52 with both guselkumab regimens.ConclusionsGuselkumab Q4W and Q8W resulted in robust and sustained improvements in PsA signs and symptoms consistently in subgroups of patients defined by diverse baseline characteristics.Trial registration numbersNCT03162796, NCT03158285.

Efficacy of Tildrakizumab Across Different Body Weights in Moderate-to-Severe Psoriasis Over 5 Years: Pooled Analyses from the reSURFACE Pivotal Studies

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Low rates of radiographic progression associated with clinical efficacy following up to 2 years of treatment with guselkumab: results from a phase 3, randomised, double-blind, placebo-controlled study of biologic-naïve patients with active psoriatic arthritis

“…These results may not be generalisable to all patients with PsA; however, it should be noted that the treatment effect with guselkumab has been observed across subgroups from DISCOVER-1 and DISCOVER-2 defined by various baseline demographic and disease characteristics. 55 In addition, 2 years may be a relatively short follow-up time for observing radiographic progression in PsA. To that end, a phase 3b study (APEX; NCT04882098) is being conducted to further evaluate the effects of guselkumab on radiographic progression in at-risk biologic-naïve patients with PsA.…”

“…As noted, previous findings from DISCOVER-1 and DISCOVER-2 have demonstrated the efficacy of guselkumab in improving signs and symptoms across several PsA disease domains across diverse patient subgroups. 55 The patients with an elevated risk of future structural damage who were enrolled in DISCOVER-2 demonstrated low rates of radiographic progression through 2 years, with 85%–90% completing the study through week 100. Results of the current post hoc analyses from DISCOVER-2 indicate that achieving low levels of clinical disease activity, following 1 or 2 years of treatment with guselkumab, is associated with less radiographic progression over 2 years.…”