Guselkumab provides durable improvement across psoriatic arthritis disease domains: post hoc analysis of a phase 3, randomised, double-blind, placebo-controlled study.

Evaluate long-term guselkumab effectiveness across Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-recognised domains/related conditions of psoriatic arthritis (PsA). Post hoc analyses used data from DISCOVER-2 (NCT03158285) biologic/Janus-kinase inhibitor-naïve participants with active PsA (≥5 swollen/≥5 tender joints, C-reactive protein ≥0.6 mg/dL), randomised (1:1:1) to guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo with crossover to guselkumab. Outcomes aligned with key GRAPPA-recognised domains of overall disease activity, peripheral arthritis, axial disease, enthesitis/dactylitis and skin psoriasis (nail psoriasis was not evaluated). PsA-related conditions (inflammatory bowel disease (IBD)/uveitis) were assessed via adverse events through W112. Least squares mean changes from baseline through W100 in continuous outcomes employed repeated measures mixed-effects models adjusting for baseline scores. Binary measure response rates were determined with non-responder imputation for missing data. 442/493 (90%) of guselkumab-randomised patients completed treatment through W100. Following early reductions in disease activity with guselkumab, durable improvements were observed across key PsA domains (swollen/tender joints, psoriasis, spinal pain, enthesitis/dactylitis) through W100. Response rates of therapeutically relevant targets generally increased through W100 with guselkumab Q4W/Q8W: Disease Activity Index for PsA low disease activity (LDA) 62%/59%, enthesitis resolution 61%/70%, dactylitis resolution 72%/83%, 100% improvement in Psoriasis Area and Severity Index 59%/53%, Psoriatic Arthritis Disease Activity Score LDA 51%/49% and minimal disease activity 38%/40%. Through W112, no cases of IBD developed among guselkumab-randomised patients and one case of uveitis was reported. In biologic-naïve patients with active PsA, guselkumab provided early and durable improvements in key GRAPPA-recognised domains through 2 years, with substantial proportions achieving important treatment targets.

Coates LC ，Gossec L ，Zimmermann M ，Shawi M ，Rampakakis E ，Shiff NJ ，Kollmeier AP ，Xu XL ，Nash P ，Mease PJ ，Helliwell PS ... -  《-》

Comparison of On-Label Treatment Persistence in Real-World Patients with Psoriatic Arthritis Receiving Guselkumab Versus Subcutaneous Interleukin-17A Inhibitors.

Psoriatic arthritis (PsA) is a chronic, multidomain, inflammatory disease requiring long-term treatment. Guselkumab, a fully human interleukin [IL]-23p19-subunit inhibitor, and the IL-17A inhibitors (IL-17Ai) ixekizumab and secukinumab are approved by the US Food and Drug Administration (FDA) for adults with active PsA. Real-world data evaluating on-label treatment persistence is an important consideration for patients. This retrospective claim-based analysis (IQVIA PharMetrics® Plus) included adults with PsA receiving guselkumab or their first subcutaneous (SC) IL-17Ai (ixekizumab/secukinumab) per FDA label ("on-label") between July 14, 2020, and June 30, 2022. Baseline demographic and disease characteristics were collected in the 12 months preceding the index date (date of first guselkumab or SC IL-17Ai claim); follow-up extended through the earlier of the end of continuous insurance eligibility or end of data availability. Baseline characteristics were balanced between the cohorts by propensity score weighting (standardized mortality ratio [SMR]). Discontinuation was defined as a gap 2 × the FDA-approved maintenance dosing interval (guselkumab:112 days; SC IL-17Ai: 56 days); on-label persistence in the weighted cohorts was assessed using Kaplan-Meier curves and compared with a Cox proportional hazards model. Weighted demographic and disease characteristics were well balanced between the cohorts (guselkumab: N = 910, mean age = 50.4 years, 60.4% female; SC IL-17Ai: N = 2740, mean age = 50.2, 59.4% female). At 12 months, the guselkumab cohort was 1.85 × more likely to remain persistent with on-label therapy vs the SC IL-17Ai cohort (p < 0.001); median time to discontinuation was not reached for guselkumab and was 12.3 months for SC IL-17Ai. At 3, 6, 9, and 12 months, persistence rates in the weighted cohorts were higher with guselkumab than with SC IL-17Ai (p < 0.001). In this real-world claims data analysis in adults with PsA, on-label persistence rates were statistically significantly higher with guselkumab, as early as 3 months, with ~ 2 × greater likelihood of persistence at 12 months relative to SC IL-17Ai.

Mease PJ ，Ferrante SA ，Shiff NJ ，Fitzgerald TP ，Chakravarty SD ，Walsh JA ... -  《-》

Durable control of psoriatic arthritis with guselkumab across domains and patient characteristics: post hoc analysis of a phase 3 study.

Evaluate patterns of stringent disease control with 2 years of guselkumab across key disease-identified domains and patient-reported outcomes (PROs) in subgroups of patients with psoriatic arthritis (PsA) defined by baseline characteristics. This post hoc analysis of DISCOVER-2 (Clinicaltrials.gov NCT03158285) evaluated biologic-naïve PsA patients (≥ 5 swollen/ ≥ 5 tender joints, C-reactive protein [CRP] ≥ 0.6 mg/dL) randomized to guselkumab every 4 weeks (Q4W); guselkumab at Weeks 0 and 4, then Q8W; or placebo with crossover to guselkumab Q4W at Week 24. Achievement of American College of Rheumatology 50/70% improvement (ACR50/70), Investigator's Global Assessment (IGA) 0, dactylitis/enthesitis resolution, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue response (≥ 4-point improvement), HAQ-Disability Index (HAQ-DI) response (≥ 0.35-point improvement), PsA Disease Activity Score (PASDAS) low disease activity (LDA), and minimal disease activity (MDA) was assessed at Weeks 24, 52, and 100 in subgroups defined by sex and baseline medication use, body mass index, PsA duration, swollen/tender joints, CRP, and psoriasis severity/extent. Patients with missing categorical response data were considered nonresponders. 442/493 (90%) guselkumab-randomized patients completed treatment through Week 100. Significant multi-domain efficacy of guselkumab versus placebo was shown across adequately sized patient subgroups. A pattern of continuous improvement was observed across key PsA domains and PROs within patient subgroups: 65%-85% of guselkumab-randomized patients had enthesitis/dactylitis resolution, 50%-70% achieved complete skin clearance, 60%-80% reported meaningful improvements in function/fatigue, 40%-65% achieved PASDAS LDA, and 35%-50% achieved MDA at Week 100. Patients with active PsA receiving guselkumab demonstrated durable achievement of stringent endpoints associated with disease control across key PsA domains and PROs, regardless of baseline characteristics. Key Points • Among biologic-naïve patients with highly active psoriatic arthritis (PsA), efficacy of guselkumab across stringent disease endpoints and patient-reported outcomes (PROs) at Week 24 was consistent regardless of baseline demographics and disease characteristics. • Within guselkumab-randomized PsA patient subgroups, major improvements in joint disease activity, complete skin clearance, dactylitis/enthesitis resolution, clinically meaningful improvements in PROs, and achievement of low overall disease activity were maintained through Week 100. • Durable stringent endpoint achievement indicating disease control was observed with guselkumab, regardless of baseline patient or disease characteristics.

Ritchlin CT ，Mease PJ ，Boehncke WH ，Tesser J ，Chakravarty SD ，Rampakakis E ，Shawi M ，Schiopu E ，Merola JF ，McInnes IB ，Deodhar A ... -  《-》

The Effect of Guselkumab on Work Productivity in Biologic-Naïve Patients with Active Psoriatic Arthritis Through Week 52 of the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Trial.

The phase 3 DISCOVER-2 trial evaluated the effect of guselkumab on impaired work productivity and nonwork activity in biologic-naïve patients with psoriatic arthritis (PsA). Adults with active PsA were randomized (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W), guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks (Q8W), or placebo (with crossover to guselkumab Q4W at week 24). Least squares mean change from baseline in Work Productivity and Activity Impairment Questionnaire for PsA (WPAI-PsA) domains and employment were assessed by treatment group. Multivariate analysis of data from weeks 0 through 24 assessed independent associations between PsA clinical features and WPAI-PsA domains. In total, 738 patients were evaluated (guselkumab Q4W n = 245; guselkumab Q8W n = 248; placebo n = 245). At week 24, improvements (reduced impairment) in presenteeism (Q4W -20.1%, Q8W -19.6%, placebo -10.5%), work productivity (Q4W -20.1%, Q8W -19.2%, placebo -10.6%), and nonwork activity (Q4W -20.5%, Q8W -21.2%, placebo -9.9%) were greater in guselkumab-treated versus placebo-treated patients. At week 52, following placebo crossover at week 24, improvements were similar among groups. Baseline absenteeism was minimal and did not change in any group. By week 52, 23.1-25.9% of guselkumab-treated patients who were unemployed at baseline were employed. All WPAI-PsA domains were positively associated with C-reactive protein level, fatigue, and pain. All domains except absenteeism were positively associated with enthesitis and Psoriasis Area and Severity Index score. Age was negatively associated with presenteeism and work productivity loss, female sex and tender joint count were positively associated with nonwork activity impairment, and dactylitis was positively associated with presenteeism. Both guselkumab regimens reduced work productivity loss and nonwork activity impairment in patients with active PsA. Association of work productivity loss and nonwork activity impairment with PsA joint and skin features suggests that improvement in both features is beneficial for optimizing improved work productivity loss and nonwork activity impairment. ClinicalTrials.gov identifier, NCT03158285.

Curtis JR ，McInnes IB ，Rahman P ，Gladman DD ，Peterson S ，Agarwal P ，Yang F ，Kollmeier AP ，Hsia EC ，Shiff NJ ，Zhou B ，Han C ，Shawi M ，Tillett W ，Mease PJ ... -  《-》

Interventions for nail psoriasis.

de Vries AC ，Bogaards NA ，Hooft L ，Velema M ，Pasch M ，Lebwohl M ，Spuls PI ... -  《-》