Background Recent guidelines from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recommend that psoriatic arthritis (PsA) therapy achieve lowest possible disease activity across 6 key domains and related conditions. 1 In the DISCOVER-1&2 trials, guselkumab (GUS) significantly improved signs and symptoms of PsA at Week (W) 24.

Objectives Evaluate GUS efficacy through W100 of DISCOVER-2 by GRAPPA-recommended PsA domains (peripheral arthritis, skin, dactylitis, enthesitis, axial disease [nails not evaluated]) and related conditions of inflammatory bowel disease (IBD) and uveitis.

Methods Enrolled adults had active PsA, were naïve to biologics/JAK inhibitors, and had ≥5 swollen and ≥5 tender joints and CRP ≥0.6 mg/dL. Randomized (1:1:1) patients (pts) received GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then every 8 weeks (Q8W); or placebo (PBO) with crossover to GUS 100 mg Q4W at W24. Outcomes selected aligned with GRAPPA-recommended domains/conditions: overall disease activity (Psoriatic Arthritis Disease Activity Score [PASDAS], Minimal Disease Activity [MDA]), peripheral arthritis (changes in Disease Activity Index for Psoriatic Arthritis [DAPSA] and clinical DAPSA [cDAPSA]), skin (Psoriasis Area and Severity Index [PASI], Investigator’s Global Assessment of psoriasis [IGA]), dactylitis (Dactylitis Severity Score [DSS]), enthesitis (Leeds Enthesitis Index [LEI]), axial disease (spinal pain) and IBD/uveitis (adverse events [AEs]). Among 493 GUS-randomized pts, change from baseline (BL) through W100 in continuous outcomes were analyzed by Repeated Measures Generalized Linear Mixed Effects Models adjusting for respective BL score and GUS regimen. Achievement of therapeutic endpoints was summarized by descriptive statistics using nonresponder imputation (NRI) for missing categorical data.

Results ~90% of GUS-randomized pts completed treatment at W100. For continuous outcomes, improvements over time in key PsA domains extended through W100 of GUS (Figure 1). Therapeutic endpoint response rates also increased incrementally through W100 (Table 1). Mean improvements and response rates were consistent across key domains with no significant difference between GUS regimens. For related conditions, 1 GUS pt had IBD and 4 had uveitis at BL and none had AE of exacerbation through W100. No pt developed IBD through W100 (vs 1 PBO pt through W24); 1 GUS pt had AE of iridocyclitis through W100 (vs 1 PBO pt through W24).

Conclusion In DISCOVER-2 bio-naïve PsA pts, both GUS regimens provided continued improvements in key GRAPPA-recommended domains of PsA through up to 2 years of treatment.