Navigating the Modern PsA Treatment Landscape

Psoriatic arthritis (PsA) management is entering a new era, driven by advances in immunopathology and an expanding arsenal of biologic and targeted synthetic therapies. A recent systematic review by Firdous et al. synthesizes data from 20 studies covering over 77,000 patients, highlighting how emerging therapies are challenging long-standing treatment hierarchies and offering more nuanced options for a disease long marked by therapeutic limitations.

Here’s how the treatment landscape is starting to shift.

Beyond TNF Inhibition: The Shift to IL-17 and IL-23

TNF inhibitors like etanercept, infliximab, and adalimumab have dominated PsA treatment. Their efficacy in joint and skin manifestations is well established with ACR20 response rates between 62% and 73%, and they continue to offer robust disease control in many cases. However, diminishing efficacy, adverse events, and secondary failure have led researchers and clinicians to explore upstream and alternative immune targets.

Looking at IL-17 and IL-23 pathways, agents such as secukinumab, ixekizumab, and guselkumab—and more recently, bimekizumab—have emerged as potent modulators of disease activity, particularly in patients unresponsive to TNF inhibitors. Guselkumab, an IL-23p19 inhibitor, and bimekizumab, a dual inhibitor of IL-17A and IL-17F, not only maintain high ACR20/50/70 rates but also exhibit superior performance in cutaneous domains (e.g., PASI90/100 responses) and harder-to-treat phenotypes such as enthesitis and dactylitis.

These agents limit off-target immune modulation and offer better tolerability in long-term use, although long-term safety data and comparative trials with other biologic classes remain limited.

JAK and TYK2 Inhibitors: Synthetics Join the Biologic Conversation

Though not biologics, targeted synthetic DMARDs (tsDMARDs) like apremilast and deucravacitinib are now established components of the PsA treatment landscape. Apremilast has demonstrated long-term safety and tolerability, though its role in biologic-refractory PsA remains unclear. Deucravacitinib, a selective TYK2 inhibitor, has shown early promise with ACR20 responses exceeding 60% in some trials, but requires further study to define its role in the treatment sequence.

Unanswered Questions and Unresolved Gaps

Despite notable therapeutic advances, several critical uncertainties persist in PsA management. Conventional synthetic DMARDs such as leflunomide and cyclosporine continue to be used, but they are clearly surpassed in both efficacy and tolerability by newer biologics. Intriguingly, one large retrospective cohort study suggests biologics may reduce the incidence of PsA in patients with psoriasis compared to methotrexate, suggesting a potential role in disease prevention.

At the same time, several critical gaps persist. Pediatric and early-onset PsA remain vastly underrepresented in clinical trials, and direct comparisons between biologics and targeted therapies are rare, leaving clinicians with limited guidance on sequencing or switching between these classes. Additionally, cost-effectiveness analyses are largely missing from the literature, raising equity concerns as newer agents enter the market with premium pricing.

Towards Individualized PsA Management

The current evidence supports a shift from a linear treatment algorithm to a phenotype-guided, individualized strategy:

• TNF inhibitors remain well-established options with strong efficacy in joint and skin manifestations.
• IL-17 and IL-23 pathway inhibitors have expanded treatment options for patients with inadequate responses to TNF inhibitors, demonstrating meaningful efficacy across multiple disease domains. IL-17 pathway agents have shown improvements in difficult-to-treat manifestations such as enthesitis and dactylitis, with Candida infections reported for bimekizumab, while IL-23 inhibitors offer selective immune targeting with favorable efficacy and safety profiles.
• Targeted synthetic DMARDs (tsDMARDs), including apremilast and deucravacitinib, represent additional options with generally favorable safety and modest but clinically meaningful efficacy, though their optimal placement in treatment algorithms continues to evolve.

As the therapeutic landscape for PsA continues to evolve, so must clinical frameworks that prioritize long-term outcomes, safety, and patient-centric care.

Reference

Firdous S, Amjad H, Choudhary MU, et al. Emerging biological therapies for psoriatic arthritis: a systematic review. Medicine. 2025;104(42):e45259. doi:10.1097/MD.0000000000045259.