Guselkumab Led to Improvements Over Several Psoriatic Arthritis Disease Domains

Laura C. Coates, MBChB, MRCP, PhD

Credit: X (Twitter)

Guselkumab treatment led to early and durable improvements in key Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-recognized areas In biologic-naïve psoriatic arthritis (PsA) patients through 2 years, according to new findings.¹

These findings represented the conclusion of a new post-hoc analysis of the phase 3, double-blind, randomized, placebo-controlled trial assessing treatment of PsA with guselkumab among adults with active disease. The phase 3 analysis had been carried out in the period between July 2017 - November 2020.

This new post-hoc analysis was led by Laura C. Coates, MBChB, MRCP, PhD, from the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences at University of Oxford in the UK. Coates and colleagues noted the 6 GRAPPA disease domains, adding that the GRAPPA guidelines urge achievement of the lowest possible disease activity level across all domains.²

“Informed by the GRAPPA treatment goal of achieving the lowest possible level of disease activity in all affected disease domains…the objective of the present post hoc analysis was to evaluate the long-term (Week 100) effectiveness of guselkumab across GRAPPA-identified PsA domains and related conditions assessed in DISCOVER-2,” Coates and colleagues wrote.

Background and Methods

As mentioned previously, the research team carried out their post-hoc analyses of the phase 3 data drawn from the DISCOVER-2 study, a trial which had been aimed at subjects who had been biologic or Janus kinase inhibitor-naïve and active PsA. Active disease had been defined as maintaining 5 swollen joints minimum as well as 5 tender joints at least and a C-reactive protein level of 0.6 mg/dL or more.

Study subjects were randomized using a 1:1:1 ratio, being treated with either guselkumab every 4 weeks (Q4W) or the same treatment every 8 weeks (Q8W). The alternative was receiving a placebo with crossover to guselkumab in the subsequent period.

The investigators looked at several different domains highlighted by GRAPPA, which included peripheral arthritis, overall disease activity, enthesitis/dactylitis, axial disease, and skin psoriasis. Additionally, the research team assessed PsA-connected issues including uveitis and inflammatory bowel disease (IBD), evaluated through adverse events (AEs) reported up to the 112-week mark.

The team looked at post-baseline changes through the 100-week mark in continuous outcomes, implementing repeated measures mixed-effects models as well as adjusting for patients’ scores at baseline. Rates of response rates in binary measures were identified by the investigators through the use of non-responder imputation methods.

Findings

The research team reported that 90% of the subjects who had been randomized to be treated with guselkumab finished up the process by the 100-week point. Following an initial disease activity decrease with the drug, the team identified sustained signs of success over several of the aforementioned domains of PsA up to Week 100.

The investigators found that the participants’ rates of reaching their therapeutic targets showed signs of increasing through the 100-week mark with the drug administered to subjects Q4W or every 8 weeks (Q8W). These signs of improvement included low disease activity (LDA) achievement according to the Disease Activity Index for PsA being 62% with Q4W and 59% after Q8W.

The research team also noted enthesitis rates of resolution being 61% and 70% following Q4W and Q8W, respectively, and dactylitis resolution rates being 72% and 83% with Q4W and Q8W, respectively. Furthermore, the team found subjects with 100% improvement in their Psoriasis Area and Severity Index scores (PASI 100) were 59% and 53% with Q4W and Q8W, respectively.

Lastly, those reporting LDA according to the Psoriatic Arthritis Disease Activity Score were 51% and 49% with Q8W and Q4W, respectively, as well as minimal disease activity achievement among 38% and 40% with Q4W with Q8W, respectively.

The investigators found no instances up to the 112-week point of IBD among subjects who had been given guselkumab. Additionally, only a single case of uveitis was observed.

“No exacerbations or new onset of IBD were reported, with a single occurrence of uveitis observed through Week 100 in guselkumab-treated patients, aligning with the established safety profile of guselkumab,” they wrote.

References

1. ^{Coates LC, Gossec L, Zimmermann M, et al. Guselkumab provides durable improvement across psoriatic arthritis disease domains: post hoc analysis of a phase 3, randomised, double-blind, placebo-controlled study. RMD Open. 2024;10(1):e003977. Published 2024 Mar 26. doi:10.1136/rmdopen-2023-003977.}
2. ^{Coates LC, Soriano ER, Corp N, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021. Nat Rev Rheumatol 2022;18:465–79. doi:10.1038/s41584-022-00798-0.}