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.
washington; seattle; swedish; arthritis, psoriatic; biological therapy; therapeutics; Adult; Antibodies, Monoclonal, Humanized; Arthritis, Psoriatic; Clinical Trials, Phase III as Topic; Demography; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
OBJECTIVES: To 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.
METHODS: Adults 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.
RESULTS: Baseline 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.
CONCLUSIONS: Guselkumab 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 NUMBERS: NCT03162796, NCT03158285.
Orthopedics & Sports Medicine
Ritchlin, Christopher T; Mease, Philip; Boehncke, Wolf-Henning; Tesser, John; Schiopu, Elena; Chakravarty, Soumya D; Kollmeier, Alexa P; Xu, Xie L; Shawi, May; Jiang, Yusang; Sheng, Shihong; Wang, Yanli; Xu, Stephen; Merola, Joseph F; McInnes, Iain B; and Deodhar, Atul, "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." (2022). Articles, Abstracts, and Reports. 5948.