IL-23 Inhibitors Show Broad PsA Control, with Important Gaps Remaining

For patients with psoriatic arthritis (PsA), achieving comprehensive disease control across both articular and extra-articular manifestations remains a clinical challenge. While TNF inhibitors have long been the mainstay of biologic therapy, limitations such as primary and secondary non-response necessitate alternative treatment options.

That’s why a recent systematic review and meta-analysis published in Frontiers in Pharmacology synthesizes data from six randomized controlled trials to evaluate the efficacy and safety of IL-23 inhibitors in this population.

Targeting the IL-23/IL-17 Axis

For some background, interleukin-23 (IL-23) plays a pivotal role in the differentiation and maintenance of pathogenic Th17 cells, which contribute to synovial inflammation, bone erosion, and entheseal damage. By inhibiting IL-23, this inflammatory cascade is interrupted.

And so this meta-analysis evaluated three IL-23p19 inhibitors—guselkumab, risankizumab, and tildrakizumab—across trials involving patients with active PsA. The baseline characteristics of the enrolled patients indicated a moderate to high degree of cutaneous disease severity and considerable musculoskeletal involvement.

Comprehensive Disease Control

The pooled analysis demonstrated that IL-23 inhibitors were significantly more effective than placebo across multiple disease domains:

• Joint Symptoms: Patients receiving IL-23 inhibitors showed significantly higher response rates for ACR20 (RR = 1.86; 95% CI: 1.69–2.05), ACR50 (RR = 2.75; 95% CI: 2.31–3.29), and ACR70 (RR = 3.06; 95% CI: 2.29–4.10).
• Skin Clearance: The likelihood of achieving PASI90 was markedly higher in the treatment group (RR = 5.98; 95% CI: 4.68–7.64), highlighting the therapeutic benefit for cutaneous disease.
• Minimal Disease Activity: IL-23 inhibition resulted in a significantly higher rate of achieving minimal disease activity (MDA) compared to placebo (RR = 2.85; 95% CI: 2.30–3.54).
• Specific Manifestations: The treatment group exhibited greater resolution of both enthesitis (RR = 1.46; 95% CI: 1.29–1.64) and dactylitis (RR = 1.39; 95% CI: 1.20–1.61).

A Favorable Safety Profile

The safety profile of IL-23 inhibitors in PsA is generally favorable, with adverse event rates similar to placebo. Common adverse events include nasopharyngitis, upper respiratory tract infections, and injection-site reactions. No increase in serious infections, malignancy, or cardiovascular events was noted in the analyzed trials.

Additionally, transient, asymptomatic elevations in hepatic transaminases are rare and typically do not require treatment discontinuation.

Considerations for Clinical Practice

While the meta-analysis provides robust evidence for the short- to medium-term efficacy of IL-23 inhibitors, there are a few limitations to consider. Most included studies had follow-up periods of 1 to 2 years, necessitating further extended follow-up studies to fully understand long-term durability and safety. Additionally, current evidence suggests limited benefit in axial disease, which appears to be driven predominantly by IL-17A and TNF-α pathways independent of IL-23 signaling.

For clinicians managing PsA, these findings support the integration of IL-23 inhibitors into treatment strategies, particularly for individuals with multidomain involvement, extensive psoriasis, or inadequate response to conventional therapies. As the therapeutic landscape evolves, IL-23 inhibitors offer a targeted and versatile option for comprehensive disease management.

Reference:
Zeng J, Lin L, Li W, et al. Clinical benefits and complication profile of IL-23 inhibitors in patients with psoriatic arthritis: a systematic review and meta-analysis. Front Pharmacol. 2025;16:1669786. doi:10.3389/fphar.2025.1669786