Guselkumab Significantly Improves Disease Activity in PsA Over 100 Weeks

Laura C Coates, MBChB, MRCP, PhD

Credit: University of Oxford

A substantial proportion of patients with psoriatic arthritis (PsA) receiving guselkumab were able to achieve individual minimal disease activity (MDA) criteria, with continued improvements through week 100, according to a study published in BMC Rheumatology.¹

Interestingly, the achievement of physician-assessed MDA was significantly faster when compared with patient-driven criteria. Investigators believe these results have the potential to optimize both the achievement and sustainability of MDA using a multidisciplinary approach to disease management, which should include both lifestyle and medical interventions.

Guselkumab is a fully human monoclonal antibody designed to target the p19 subunit of interleukin (IL)-23 and is approved to treat adult patients with moderate to severe psoriasis or active PsA. Previous research has shown a favorable safety profile and is linked to significant symptom improvement across PsA domains.²

“Despite the availability of increasingly effective treatments in recent years, a minority of PsA patients achieve MDA and few realize sustained MDA,” wrote Laura C Coates, MBChB, MRCP, PhD, associate professor at the Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK, and colleagues. “Of note, criteria for patient-reported domains of MDA may be less frequently achieved, owing to comorbidities associated with systemic inflammatory conditions, including fibromyalgia and obesity, that may indirectly contribute to unmet MDA domain criteria.”

Investigators assessed the trajectory of, and factors contributing to, achievement of the individual criteria of MDA in patients with PsA receiving guselkumab in the phase 3, randomized, placebo-controlled DISCOVER-2 trial. In the original study, a total of 739 patients with active disease despite standard treatment who were biologic and Janus kinase (JAK) inhibitor-naïve were included in the analysis. Patients were randomized 1:1:1 to receive either guselkumab 100 mg every 4 weeks, guselkumab 100 mg at week 0, week 4, and then every 8 weeks, or placebo.

In this post hoc analysis, those who were treated with guselkumab (n = 493) were included and pooled. The longitudinal trajectories of MDA criterion achievement through week 100 were determined using non-responder imputation, while the time to achieve each criterion was assessed using Kaplan-Meier analysis. Cox regression and logistic regression were used to identify any contributing factors impacting the time to achieve each criterion and the achievement at week 100, respectively.

In this patient population, continuous improvement across all MDA domains was demonstrated over the 100-week timeframe, with approximately 70% of patients achieving near remission in swollen joint count (SJC), enthesitis, and the Psoriasis Area and Severity Index (PASI). However, the median times to achieve individual criteria differed significantly (P < .0001). SJC ≤ 1 (20 weeks), PASI ≤ 1 (16 weeks), and ≤ 1 tender entheses (16 weeks) were met much faster than patient-reported criteria, including pain ≤ 15 mm, the Health Assessment Questionnaire-Disability Index (HAQ-DI) ≤ .5, tender joint count ≤ 1, and the patient global assessment of arthritis and psoriasis ≤ 20 mm.

Significant predictors of longer time to achieve MDA determined using patient-reported criteria included older age, increased body mass index, higher baseline domain scores, and worse fatigue.

Investigators noted the post hoc analysis study design as a limitation, although a statistical analysis plan was prepared to assess factors linked with the trajectory of MDA response components in this patient population. Additionally, the median time to achieve minimal PASI may have been overestimated as it was not assessed before week 16. Finally, results may not be generalizable to real-world populations, particularly in smaller patient subgroups, such as those with a history of depression, suicidal ideation, or fibromyalgia.

“The present findings agree with analyses demonstrating a long-lasting effect of guselkumab across key PsA domains described by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), along with multi-domain efficacy regardless of baseline demographic and disease characteristics,” investigators concluded. “Findings are also consistent with previous analyses demonstrating the utility of guselkumab in providing stringent and sustained control of disease activity across multiple PsA domains, many of which are included in the MDA definition, such as peripheral joint symptoms, psoriatic skin lesions, enthesitis, physical function, and patient pain.”

References

1. ^{Coates LC, Rahman P, Mease PJ, et al. Continuous improvement through differential trajectories of individual minimal disease activity criteria with guselkumab in active psoriatic arthritis: post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled study. BMC Rheumatol. 2024;8(1):6. Published 2024 Feb 4. doi:10.1186/s41927-024-00375-w}
2. ^{Gooderham MJ, Papp KA, Lynde CW. Shifting the focus - the primary role of IL-23 in psoriasis and other inflammatory disorders. J Eur Acad Dermatol Venereol. 2018;32:1111–9. https://doi.org/10.1111/jdv.14868.}