Low Disease Activity Linked to Less Radiographic Progression in Patients With PsA Receiving Guselkumab

Guselkumab-treated patients with psoriatic arthritis (PsA) who achieved low levels of disease activity, including minimal disease activity (MDA), were more likely to report reduced rates of radiographic progression, according to a study published in Rheumatic and Musculoskeletal Diseases.¹ Further, radiographic non-progressors achieved patient-reported MDA criteria of normalized physical function and minimal pain more often than radiographic non-responders.

“Uncontrolled inflammation resulting from delayed therapy increases the risk of structural joint damage in PsA,” Alice Bendix Gottlieb, MD, PhD, Medical Director, Mount Sinai Beth Israel Dermatology, and a team of investigators, stated. “Structural damage, in turn, is associated with greater impairment of physical function and disability, which may be partly irreversible and lead to long-term impairment of health-related quality of life (HRQoL) and work productivity… Thus, limiting structural damage is an important treatment objective when addressing the potential manifestations of this lifelong disease.”

Previous analysis from the DISCOVER-1 and DISCOVER-2 trials observed that treatment with guselkumab, a fully human interleukin-23p19 inhibitor, resulted in improvements in a variety of signs and symptoms across several PsA disease domains.²

In the Phase 3, placebo-controlled DISCOVER-2 trial, biologic-naïve adult patients with active PsA were randomized (1:1:1) to receive guselkumab 100 mg ever 4 weeks (Q4W); guselkumab 100 mg at week 0, 4, and then every 8 weeks (Q8W); or switched from placebo to Q4W at week 24. Active PsA was defined as 5 or more swollen joints, 5 or more tender joints, and C-reactive protein ≥0.6 mg/dL. Radiographs of the hands and feet were conducted at week 0, week 24, week 52, and week 100, which were scored using the PsA-modified van der Heijde-Sharp (vdH-S) scores.

In post hoc analyses, mean changes in these scores were reviewed in terms of achievement of the American College of Rheumatology 20/50/70 response, low disease activity (LDA), and normalized physical function. LDA was defined as Disease Activity in Psoriatic Arthritis (DAPSA) ≤14 or Psoriatic ArthritiS Disease Activity Score (PASDAS) ≤3.2, or very low disease activity/minimal disease activity (VLDA/MDA). Physical function was determined via the Health Assessment Questionnaire-Disability Index (HAQ-DI). Response rates for obtaining MDA/VLDA were evaluated among patients with and without radiographic progression.

Of the 739 patients enrolled in DISCOVER-2, 664 continued guselkumab treatment at week 52 and were subsequently included in the post-hoc analyses. A total of 64% of patients in both groups were able to achieve ACR20 response at week 24 compared with 33% of patients receiving placebo (P <0.0001). Mean changes in vdH-S scores from weeks 0 to 100 were 1.7 in the Q4W group and 1.5 in the Q8W group.

Those who achieved ACR20/50/70, DAPSA LDA, PASDAS, LDA, VLDA, MDA, and normalized physical function reported smaller mean changes in vdH-S scores when compared with non-responders at both week 52 (0.2 – 1.2 vs 1.7 – 4.1, respectively) and week 100 (0.3 – 1.2 vs 2.0 – 4.6, respectively).

Compared with patients with radiographic progression, those without progression were more likely to achieve MDA criteria regarding swollen and tender joint counts, patient-reported pain and global assessment, and normalized physical function through week 100.

The DISCOVER-2 trial was not designed to evaluate radiographic progression in the subgroups. Therefore, results may be prone to variability in radiographic scores. Although findings may not be generalizable to all patients with PsA, guselkumab treatment has been evaluated across a variety of subgroups in the DISCOVER-1 and DISCOVER-2 studies. Additionally, 2 years could be considered a short follow-up period for radiographic progression in this patient population. To mitigate this, a Phase 3b study is currently being conducted to further determine the effects of guselkumab treatment on radiographic progression in at-risk, biologic-naïve patients with PsA.

“These results underscore the importance of timely treatment for PsA and suggest that optimizing treatment decisions to achieve low levels of disease activity across multiple PsA domains may ultimately improve long-term structural damage outcomes, thus preserving overall physical function,” investigators concluded.

References

1. ^{Gottlieb AB, McInnes IB, Rahman P, et al. Low rates of radiographic progression associated with clinical efficacy following up to 2 years of treatment with guselkumab: results from a phase 3, randomised, double-blind, placebo-controlled study of biologic-naïve patients with active psoriatic arthritis. RMD Open. 2023;9(1):e002789. doi:10.1136/rmdopen-2022-002789}
2. ^{Ritchlin CT, Mease PJ, Boehncke W-H, et al. Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: pooled results through week 52 of two phase III, randomised, placebo-controlled studies. RMD}