Guselkumab Resolves Most Psoriatic Arthritis Dactylitis at 1 Year

Dennis McGonagle, PhD

Credit: University of Leeds

Approximately three-fourths of patients with psoriatic arthritis receiving guselkumab achieved complete resolution of their dactylitis at 1 year, according to findings from a pair of phase 3 studies.¹

In pooled data from the 52-week DISCOVER-1 and DISCOVER-2 trials, investigators observed that not only did most patients with psoriatic arthritis achieve full reduction of swelling in their digits and joints with the biologic therapy—such treated patients were also more likely to achieve metrics of disease improvement.

The pivotal DISCOVER trials were responsible for confirming efficacy and safety outcomes with guselkumab in the treatment of active psoriatic arthritis and moderate-to-severe plaque psoriasis through 24 and 52 weeks. DISCOVER-2 additionally provided insight into the biologic agent’s impact on radiographic progression through 2 years of treatment.

Led by Dennis McGonagle, PhD, professor of investigative rheumatology at the University of Leeds School of Medicine, investigators conducted a prespecified analysis of pooled data from both trials to interpret the specific impact of guselkumab on psoriatic arthritis patients with and without dactylitis. They sought outcomes including resolution of the common arthritis condition, and improvements in other domains of psoriatic arthritis.

As they noted, dactylitis is generally a clinical indication of more severe disease phenotype among patients with early psoriatic arthritis—emphasizing the need for timely and efficient treatment of the condition.

“Development of dactylitis is a predictor of future radiographic damage, and patients with PsA with dactylitis and/or enthesitis report higher levels of physical disability, poorer functional status, and greater pain and fatigue than patients without these disease features,” they wrote. “Furthermore, resolution of dactylitis is associated with improvements in physical function, health-related quality of life, and pain.”

The DISCOVER trials randomized patients 1:1:1 to either subcutaneous 100 mg guselkumab injections at weeks 0, 4, then every 4 or 8 weeks; or placebo with crossover to guselkumab at week 24. Dactylitis severity score (DSS), which grades burden between 0 – 60 (0-3 per digit), was determined for patients by independent assessors.

McGonagle and colleagues determined dactylitis resolution per DSS 0, as well as improvements of ≥20%, ≥50%, and ≥70% from baseline through week 52.They additionally interpreted patient outcomes per ACR50 scores, tender/swollen joints, low disease activity, and radiographic progression, all stratified by dactylitis status, at weeks 24 and 52.

The final assessment included 1118 patients with available dactylitis data, of whom 473 (42%) had DSS ≥1 at baseline. Dactylitis was prevalent in a mean 3.4 fingers and 3.2 toes. Patients baseline dactylitis additionally had more mean severe joint and skin disease status than those without.

Approximately three-fourths (75%) of patients randomized to guselkumab who had baseline dactylitis achieved DSS 0 by week 52; another 80% achieved a severity score improvement of ≥70%.

New-onset dactylitis was uncommon among patients receiving guselkumab who had no disease at baseline. Investigators additionally observed a correlation between guselkumab-treated patients who achieved DSS 0 and achievement of ACR50, ≥50% reduction in tender and swollen joints, and low disease activity at both weeks 24 and 52 than treated patients who did not achieve DSS 0.

“More than half of all guselkumab-randomized patients achieved 20% or more DSS improvement by Week 4, 50% or more improvement by Week 8, and 70% or more improvement by Week 16,” investigators wrote. “Owing to relatively high placebo responses at Weeks 4 and 8, separation between guselkumab and placebo first became apparent (nominal P <.05) at Week 16.”

The team concluded the biologic injection was efficacious in dactylitis resolution across a wide swath of patients with psoriatic arthritis, emphasizing the benefit of inhibiting interleukin 23 (IL-23) inflammation in controlling the critical component of psoriatic disease.

“By selectively inhibiting the p19 subunit of IL-23, guselkumab promotes sustained resolution of dactylitis, which is associated with achievement of LDA, lower rates of radiographic progression, and achievement of other important treatment goals that may improve overall long-term outcomes in patients with psoriatic arthritis,” they wrote.

References

1. ^{McGonagle D, McInnes IB, Deodhar A, et al. Guselkumab, a Selective Interleukin-23 p19 Subunit Inhibitor, Resolves Dactylitis in Patients With Active Psoriatic Arthritis: Pooled Results Through Week 52 From Two Phase 3 Studies [published online ahead of print, 2023 Mar 7]. ACR Open Rheumatol. 2023;10.1002/acr2.11537. doi:10.1002/acr2.11537}