Guselkumab Demonstrates Sustained Improvements in Patients With Active Psoriatic Arthritis

In an interview with HCPLive Rheumatology, Carlo Selmi, MD, PhD, director of the Residency School of Emergency Medicine at Humanitas University, discussed the recent results of a post-hoc analysis of the phase 3b COSMOS trial which showed guselkumab treatment demonstrated sustained improvements across all minimal disease activity (MDA) domains in adult patients with psoriatic arthritis (PsA) who had inadequate response to ≥1 tumor necrosis factor inhibitors (TNF). The findings were presented at the European Congress of Rheumatology (EULAR) 2023.

Carlo Selmi, MD, PhD

Credit: Humanitas University

Guselkumab, a fully human selective interleukin-23 inhibitor (IL-23), is the only drug of its kind approved for this patient population.

Although a previous study showed sustained MDA is generally only achieved by a small proportion of patients with PsA receiving biologic therapy, guselkumab was able to provide MDA improvements from baseline through week 48. A separate post-hoc analysis also identified factors influencing disagreement between the physician and patient global assessments, including physical aspects of health-related quality of life, fatigue, and patient-reported pain.

A total of 189 patients were included in the analysis of the multicenter, randomized, double-blind, placebo-controlled trial. At week 24 and 48, response rates for the Psoriasis Area and Severity Index (PASI) were 66.8% and 81.5%, respectively, and the Leeds Enthesitis Index (LEI) response rates were 74.5% and 79.8%, respectively. The Health Assessment Questionnaire Disability Index (HAQ-DI) reported 26.1% and 37.0% improvements at week 24 and 48, respectively, and patient pain response rates were 14.7% and 30.6%, respectively.

Physician-reported domains, such as LEI, swollen joint count (SJC), and PASI, were attained at faster rates when compared with patient-driven domains.

Why did your team choose to assess guselkumab for this specific patient population (ie, patients with PsA who previously had an inadequate response to one to two tumor necrosis factor inhibitors)?

Current recommendations place all mechanisms of action for biologics on the same level as first or subsequent lines of treatments. However, in most countries, anti-TNFa (particularly biosimilars) constitute the majority of chosen first-line (and often second-line) biologics.

Furthermore, patients that have failed 1 or 2 biologics are a very challenging population to treat and thus a largely unmet need in the management of PsA. Based on this rationale, investigating IL-23-blocking guselkumab in this population was crucial and led to the design of the COSMOS trial.

Why was it important for your team to focus on patient-reported outcomes as well as clinical outcomes?

These 2 measures of outcome represent the 2 sides of the coin of treatment efficacy and in many cases are discrepant during the therapy, particularly due to non-inflammatory pain. As such, it is important to understand whether the timing of these 2 families of response differs.

Did the results of this study surprise you?

Until now, we only suspected the mechanisms of objective and patient-reported outcomes were discrepant. In the case of IL-23 inhibition, we hypothesized a direct effect on symptoms, besides inflammation.

What is the clinical significance of these results?

These are of major importance to know how to explain what the patient should expect over time, particularly in terms of symptoms.

Were there any strengths or limitations that you’d like to highlight?

The major strength was overcoming the limits of composite measures, such as MDA, which includes 7 items put on the same level.

What are the next steps for your team?

These results should be now observed in a real-life setting as well as long-term.

Is there anything else our audience needs to know?

This study underlines the major heterogeneity of psoriatic arthritis and the need for a personalized approach.