Guselkumab Efficacy in Biologic-Naïve Participants with Psoriatic Arthritis and Severe Disease Activity: Post Hoc Analysis of a Phase 3 Study

Introduction: 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). Methods: 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. Results: 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. Conclusion: 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. Trial Registration: ClinicalTrials.gov, NCT03158285.