biostudies-literatureUnknown12(5)Ritchlin CTJohnson and Johnson<h4>Introduction</h4>The aim of this study was to evaluate guselkumab efficacy through week 100 in participants with psoriatic arthritis (PsA) and severe disease activity or patient global assessment (PtGA).<h4>Methods</h4>This post hoc analysis utilized DISCOVER-2 (NCT03158285) data from 739 biologic-naïve adults with active PsA (≥ 5 swollen/tender joints, C-reactive protein  ≥ 0.6 mg/dL) randomized to guselkumab every 4 weeks (Q4W) or at weeks 0 and 4, then every 8 weeks (Q8W); or placebo with crossover to guselkumab Q4W at week 24. Severe disease activity was defined as clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) > 27, Psoriatic Arthritis Disease Activity Score (PASDAS) ≥ 5.4, and PtGA Arthritis + Psoriasis ≥ 80 mm. Least squares mean (LSM) changes in cDAPSA, PASDAS, and PtGA were estimated with mixed models for repeated measures adjusted for baseline factors.<h4>Results</h4>Baseline characteristics among 648 (88%), 639 (86%), and 218 (29%) participants meeting the cDAPSA, PASDAS, and PtGA criteria for severe disease activity, respectively, were generally balanced across cohorts. LSM improvements from baseline with guselkumab Q4W/Q8W vs. placebo were -5.9 (p = 0.3905)/-7.2 (p = 0.0379) for cDAPSA at week 2; -1.5/-1.5 for PASDAS (both p < 0.0001); and -30.0/-32.1 for PtGA at week 8 (both p < 0.01). Differences vs. placebo increased through week 24 in the respective cohorts with guselkumab Q4W/Q8W: -9.8/-9.0, -1.1/-1.1, -24.0/-20.2 (all p < 0.0001). Through week 100 of guselkumab Q4W/Q8W treatment, LSM improvements of 69/74%, 52/54%, and 64/63% from baseline in cDAPSA (-35.9/-35.6), PASDAS (-3.6/-3.7), and PtGA (-56.8, -55.5), respectively, were observed. Regardless of severe disease activity definition, approximately 80% of guselkumab-randomized participants who achieved low disease activity at week 24 maintained this response at week 100.<h4>Conclusion</h4>In biologic-naïve participants with PsA and severe disease activity, guselkumab demonstrated early and durable clinically meaningful improvements in key PsA domains through 2 years.<h4>Trial registration</h4>ClinicalTrials.gov, NCT03158285.Rheumatology and therapy925-940https://www.ebi.ac.uk/biostudies/studies/S-EPMC12450146biostudies-literatureGuselkumab Efficacy in Biologic-Naive Participants with Psoriatic Arthritis and Severe Disease Activity: Post Hoc Analysis of a Phase 3 Study.PMC12450146Chimenti MSRitchlin CTDeodhar ARampakakis ENantel FSharaf MLavie FLubrano ELeibowitz EfalseGuselkumab Efficacy in Biologic-Naive Participants with Psoriatic Arthritis and Severe Disease Activity: Post Hoc Analysis of a Phase 3 Study.<h4>Introduction</h4>The aim of this study was to evaluate guselkumab efficacy through week 100 in participants with psoriatic arthritis (PsA) and severe disease activity or patient global assessment (PtGA).<h4>Methods</h4>This post hoc analysis utilized DISCOVER-2 (NCT03158285) data from 739 biologic-naïve adults with active PsA (≥ 5 swollen/tender joints, C-reactive protein  ≥ 0.6 mg/dL) randomized to guselkumab every 4 weeks (Q4W) or at weeks 0 and 4, then every 8 weeks (Q8W); or placebo with crossover to guselkumab Q4W at week 24. Severe disease activity was defined as clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) > 27, Psoriatic Arthritis Disease Activity Score (PASDAS) ≥ 5.4, and PtGA Arthritis + Psoriasis ≥ 80 mm. Least squares mean (LSM) changes in cDAPSA, PASDAS, and PtGA were estimated with mixed models for repeated measures adjusted for baseline factors.<h4>Results</h4>Baseline characteristics among 648 (88%), 639 (86%), and 218 (29%) participants meeting the cDAPSA, PASDAS, and PtGA criteria for severe disease activity, respectively, were generally balanced across cohorts. LSM improvements from baseline with guselkumab Q4W/Q8W vs. placebo were -5.9 (p = 0.3905)/-7.2 (p = 0.0379) for cDAPSA at week 2; -1.5/-1.5 for PASDAS (both p < 0.0001); and -30.0/-32.1 for PtGA at week 8 (both p < 0.01). Differences vs. placebo increased through week 24 in the respective cohorts with guselkumab Q4W/Q8W: -9.8/-9.0, -1.1/-1.1, -24.0/-20.2 (all p < 0.0001). Through week 100 of guselkumab Q4W/Q8W treatment, LSM improvements of 69/74%, 52/54%, and 64/63% from baseline in cDAPSA (-35.9/-35.6), PASDAS (-3.6/-3.7), and PtGA (-56.8, -55.5), respectively, were observed. Regardless of severe disease activity definition, approximately 80% of guselkumab-randomized participants who achieved low disease activity at week 24 maintained this response at week 100.<h4>Conclusion</h4>In biologic-naïve participants with PsA and severe disease activity, guselkumab demonstrated early and durable clinically meaningful improvements in key PsA domains through 2 years.<h4>Trial registration</h4>ClinicalTrials.gov, NCT03158285.2025-01-01T00:00:00Z2025 Oct2026-06-03T15:39:22.912Z2026-05-30T03:07:51.031ZS-EPMC124501464069016310.1007/s40744-025-00777-3