Impact of TNFi, IL-17Ai Treatments on Psoriatic Arthritis Biomarkers

Patients with psoriatic arthritis (PsA) responding to TNFi treatment may show a substantial decrease in pro-inflammatory cytokines IL-6 as well as an increase in anti-inflammatory IL-10, according to new findings.¹

These findings and several others were the results of new research evaluating the differing changes in PsA patients’ cytokine levels, specifically when comparing treatment responders and non-responders. This research was led by Marie Skougaard, from The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg in Denmark.

“The primary aim of this study was to assess the effect of medical treatments, TNFi and IL-17Ai, on the levels of 54 cytokines, chemokines, and additional biomarkers in PsA patients stratified by the effect of treatment,” Skougaard and colleagues wrote.

Skougaard and colleagues noted that their secondary goal of the analysis was to evaluate links between biomarkers at the point of baseline and the clinical- and patient-reported outcomes of individuals. They also looked set out to assess differences in subjects’ biomarker levels at baseline compared to those initiating bDMARDs and methotrexate.

Background and Methods

The investigators began by noting that the current literature demonstrates the distinct effectiveness of different treatment types on the various types of manifestations of PsA among patients.²

Over the course of their research, the research team looked at a cohort of 68 individuals with PsA. This group was made up of 29 participants who had begun treatment with TNF inhibitors (TNFi), 19 who had begun IL-17A inhibitors (IL-17Ai), and 20 who had begun methotrexate.

"Inclusion and exclusion criteria have been published in the PIPA cohort article," they wrote. "An additional inclusion criterion for the current study was added to ensure different treatments including plasma samples from 68 PsA patients initiating TNFi (n = 29), IL-17i (n = 19), or methotrexate...(n = 20), which were obtained with corresponding clinical and patient-reported data from a baseline visit adjacent to treatment start and after four months of treatment."

The team explained that the baseline characteristics of the 3 patient cohorts were assessed, including age, sex, duration of disease. They also looked at several different clinical outcome measures, with the specific measures of Psoriasis Area Severity Index (PASI), Disease Activity in Psoriatic Arthritis (DAPSA), and Visual Analog Scale (VAS) for pain, and these did not show any statistically significant differences among the different treatment arms.

However, the investigators did note several differences when they compared the number of prior biological disease-modifying antirheumatic drugs (bDMARDs) and patients’ VAS scores for fatigue across the different treatment arms. A post-hoc analysis highlighted a statistically significant disparity that was found between IL-17Ai initiators and methotrexate initiators.

The research team assessed blood plasma samples and the clinical outcome measures they looked into were gathered adjacent to initiation of treatment and following a period of 4 months. The team included a commercially-accessible multiplex immunoassay to assess 54 biomarkers and mean changes were implemented by the team to determine changes over time.

Findings

Overall, the investigators found that among responders to TNFi, there was shown to be a substantial reduction in subjects’ pro-inflammatory cytokines. These included IL-6 (mean change after log transformation: -0.97, 95% CI, -4.30 - 2.37, P = .032) as well as a rise in the anti-inflammatory cytokine IL-10 (mean change: 0.38, 95% CI, 1.74 - 2.50, P = .010).

By contrast, both IL-17Ai non-responding subjects (mean change: 2.48, 95% CI, -1.46 - 6.41, P = .001) and those labeled as responders (mean change: 2.49, 95% CI, -1.84 - 6.85, P = .031) were found by the team to have exhibited a major increase in their target cytokine IL-17A.

Such data highlight the diverse cytokine level alterations seen between responders to treatment as well as non-responders. The research team noted that these data emphasize the necessity for a stronger comprehension among clinicians of the immune response mechanisms that elucidate the various responses to medical interventions among patients with PsA.

References

1. ^{Skougaard M, Søndergaard MF, Ditlev SB, Kristensen LE. Changes in Inflammatory Cytokines in Responders and Non-Responders to TNFα Inhibitor and IL-17A Inhibitor: A Study Examining Psoriatic Arthritis Patients. Int J Mol Sci. 2024;25(5):3002. Published 2024 Mar 5. doi:10.3390/ijms25053002.}
2. ^{Bravo A., Kavanaugh A. Bedside to bench: Defining the immunopathogenesis of psoriatic arthritis. Nat. Rev. Rheumatol. 2019;15:645–656. doi: 10.1038/s41584-019-0285-8.}