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 ... -  《-》

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 ... -  《-》

Long-Term Efficacy and Safety of Guselkumab, a Monoclonal Antibody Specific to the p19 Subunit of Interleukin-23, Through Two Years: Results From a Phase III, Randomized, Double-Blind, Placebo-Controlled Study Conducted in Biologic-Naive Patients With Act

To assess long-term efficacy and safety of guselkumab, an interleukin-23 p19 subunit (IL-23p19) inhibitor, in patients with active psoriatic arthritis (PsA) from the phase III DISCOVER-2 trial. In the DISCOVER-2 trial, patients with active PsA (≥5 swollen joints and ≥5 tender joints; C-reactive protein level ≥0.6 mg/dl) despite prior nonbiologic therapy were randomized to receive the following: guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks; or placebo with crossover to guselkumab 100 mg every 4 weeks, beginning at week 24. Efficacy assessments included American College of Rheumatology ≥20%/50%/70% improvement criteria (ACR20/50/70), Investigator's Global Assessment (IGA) of psoriasis score of 0 (indicating complete skin clearance), resolution of enthesitis (Leeds Enthesitis Index) and dactylitis (Dactylitis Severity Score), and changes in the Sharp/van der Heijde modified radiographic scores for PsA. Clinical data (imputed as no response/no change from baseline if missing) and observed radiographic data were summarized through week 100; safety assessments continued through week 112. Of the 739 randomized and treated patients, 652 (88%) completed treatment through week 100. Across groups of guselkumab-treated patients (including those in the placebo-guselkumab crossover group), the following findings at week 100 indicated that amelioration of arthritis signs/symptoms and extraarticular manifestations was durable through 2 years: ACR20 response (68-76%), ACR50 response (48-56%), ACR70 response (30-36%), IGA score of 0 (55-67%), enthesitis resolution (62-70%), and dactylitis resolution (72-83%). Mean changes in the Sharp/van der Heijde modified score for PsA from weeks 52 to week 100 (range 0.13-0.75) indicated that the low rates of radiographic progression observed among guselkumab-treated patients at earlier time points extended through week 100. Through week 112, 8% (5.8 per 100 patient-years) and 3% (1.9 per 100 patient-years) of the 731 guselkumab-treated patients had a serious adverse event or serious infection, respectively; 1 death occurred (road traffic accident). In biologic-naive PsA patients, guselkumab provided durable improvements in multiple disease domains with no unexpected safety findings through 2 years.

McInnes IB ，Rahman P ，Gottlieb AB ，Hsia EC ，Kollmeier AP ，Xu XL ，Jiang Y ，Sheng S ，Shawi M ，Chakravarty SD ，van der Heijde D ，Mease PJ ... -  《-》

Bimekizumab provided rapid improvements in patient-reported symptoms and health-related quality of life in patients with active psoriatic arthritis: pooled 16-week results from two phase 3 studies.

Husni ME ，Mease PJ ，Merola JF ，Tillett W ，Goldammer N ，Ink B ，Coarse J ，Lambert J ，Taieb V ，Gladman DD ... -  《-》