Catherine J. Bakewell, MD 

Key Takeaways on Inhibiting Structural Damage in Psoriatic Arthritis

In the management of psoriatic arthritis, preventing structural damage and long-term disability is a crucial goal. However, formal treatment guidelines typically emphasize the elimination of active inflammation rather than structural damage inhibition as a primary target. The current treat-to-target approach focuses on controlling swollen joints, reducing inflammatory markers, and managing clinical symptoms. Incorporating advanced imaging techniques such as ultrasound to detect synovitis and enthesitis could provide more sensitive and earlier indicators of disease activity, potentially improving patient outcomes by guiding timely therapeutic adjustments before irreversible damage occurs.

Structural damage assessment is recognized as important but is often considered a secondary domain within clinical trials and treatment strategies. This is partly due to the slow and gradual progression of joint damage in psoriatic arthritis, which can make it difficult to measure within the time frame and size of typical early-phase studies. Although larger and longer trials attempt to evaluate radiographic progression, challenges remain in interpreting these outcomes due to minimal change in placebo groups and ethical constraints on prolonged placebo use. Nonetheless, there is an expectation that structural damage should be evaluated as part of the overall clinical development and management of the disease, albeit not necessarily as a routine treat-to-target end point.

The current era offers unprecedented therapeutic options for psoriatic arthritis, with many treatments providing both efficacy and improved safety profiles. This has transformed patient care, moving away from older, less targeted therapies toward more precise and tolerable interventions. The continued evolution of treatment strategies calls for better surrogate outcome measures, such as imaging-based markers of inflammation and early damage, to be recognized by regulatory agencies. Early identification and intervention remain key to preventing irreversible joint damage, highlighting the importance of educating health care providers and patients alike about timely diagnosis and treatment initiation.

Videos

Experts discuss the evolving management of psoriatic arthritis, emphasizing that while current treat-to-target guidelines prioritize controlling inflammation over structural damage, integrating advanced imaging for earlier detection and advocating for structural damage assessment as a key outcome could enhance long-term patient outcomes amid expanding therapeutic options.

Differentiating Between IL-23 Inhibitors in Psoriatic Disease

From a clinical and mechanistic standpoint, both medications target the IL-23 p19 subunit but differ structurally, which may influence their clinical effects. One is fully human with a wild-type Fc backbone that can bind to CD64, a high-affinity receptor found on myeloid cells producing IL-23. This binding potentially allows the drug to localize directly to inflamed sites, enhancing its ability to neutralize IL-23 where it is most active. The other drug is humanized with an Fc region mutation designed to silence immune recognition, which might reduce immune system engagement but may limit its ability to concentrate at inflammation sites. These differences could explain variations in clinical efficacy, such as stronger effects on structural damage or symptom improvement seen in some study data.

Clinically, these mechanistic distinctions translate into potential practical benefits. For example, one medication’s dosing flexibility—with options to shorten intervals for heavier or biologically experienced patients—may help manage breakthrough symptoms more effectively. Although head-to-head trials are lacking, numerical trends suggest subtle differences in outcomes such as ACR scores and fatigue, with radiographic inhibition being a key differentiator. Meanwhile, the other agent’s radiographic data have not shown statistical significance, partly due to minimal disease progression in the trial population, leaving some uncertainty about its effectiveness in preventing joint damage.

Assessing structural progression in psoriatic arthritis is inherently challenging because changes are slow and may not appear in placebo groups over typical trial durations. Moreover, evolving ethical standards limit the length of placebo-controlled phases, complicating data collection. In this context, innovative imaging tools such as ultrasound—which can detect erosions earlier and more sensitively—may offer valuable surrogate end points to better evaluate treatment effects on joint damage moving forward.

Experts discuss the structural and mechanistic differences between 2 IL-23 p19 inhibitors, exploring how variations in Fc region design may influence their localization to inflamed sites and clinical efficacy—particularly in preventing structural damage—and highlight challenges in assessing progression in psoriatic arthritis trials, suggesting that advanced imaging such as ultrasound could improve future evaluations.

Guselkumab and Structural Damage Inhibition in Psoriatic Arthritis: Insights from the APEX Trial

Recent advances in clinical research have provided critical clarity around the ability of IL-23 inhibitors to inhibit structural damage in psoriatic arthritis, a key concern for clinicians considering long-term outcomes. Early trials such as DISCOVER-2 initially suggested promise, but the approved every-8-week dose of one agent narrowly missed statistical significance in halting radiographic progression. This uncertainty led to the development of a larger, more targeted study—the APEX trial—which focused on bio-naive patients with evidence of existing joint damage. Results showed that both dosing regimens significantly inhibited structural progression, providing much-needed reassurance for clinicians.

For years, many prescribers hesitated to consider IL-23 inhibitors first line for joint disease, despite their clear effectiveness in skin clearance. With the APEX data now confirming structural protection, clinicians can confidently consider these agents even for patients with more aggressive or erosive disease. This is particularly impactful given that IL-23 inhibitors offer notable advantages in safety and dosing convenience. The ability to protect joints while minimizing serious adverse effect concerns and maintaining a low-frequency dosing schedule has the potential to shift prescribing patterns, especially for patients prioritizing long-term joint function and quality of life.

The favorable safety profile of IL-23 inhibitors also streamlines patient counseling. Discussions can often be shorter and more reassuring, as concerns commonly associated with other biologic classes—such as TB reactivation, depression, or cancer risk—are not prominent in the IL-23 data. Although some safety protocols such as TB testing remain in place for insurance reasons, clinical experts increasingly see these agents as both effective and low risk. As dermatologists and rheumatologists gain more confidence from robust evidence, the role of IL-23 inhibitors as a legitimate first-line option for both skin and joint involvement is expected to grow substantially.

Experts discuss recent clinical evidence confirming that IL-23 inhibitors effectively inhibit structural damage in psoriatic arthritis—particularly highlighted by the APEX trial’s findings in bio-naive patients—reinforcing their emerging role as a safe, convenient, and increasingly preferred first-line treatment for both joint and skin manifestations.

Inhibiting Structural Damage in Psoriatic Arthritis Wwith TNF Inhibitors and IL-17 Inhibitors

In managing psoriatic arthritis, treatment decisions are often guided by both current disease severity and future risk of progression. When a patient presents with erosive disease or is considered high-risk—based on factors like such as elevated CRP, high joint counts, family history, or the presence of enthesitis and dactylitis—clinicians typically prioritize therapies that have demonstrated an ability to inhibit structural damage. Agents such as TNF inhibitors and IL-17 inhibitors are well-supported by data in this regard and are commonly used to prevent long-term joint deterioration and preserve physical function.

In dermatology, the treatment landscape has shifted significantly over time. While TNF inhibitors were once frequently used, they are now rarely prescribed unless required by step-therapy policies. IL-17 inhibitors have become the preferred option for many clinicians due to their superior efficacy in clearing skin lesions and comparable joint effectiveness. Additionally, the convenience and quick onset of these medications make them appealing for patients with both skin and joint involvement. Findings from hHead-to-head trials have confirmed their joint efficacy, supporting their broader adoption across specialties.

There has also been a growing preference for IL-23 inhibitors, particularly in dermatologic settings. These agents are favored for their excellent safety profile, infrequent dosing schedules, and strong patient adherence seen in data from real-world studies. While IL-17 inhibitors may offer slightly better skin outcomes in some cases, IL-23 inhibitors are increasingly viewed as a balanced option for treating psoriatic disease. Their favorable safety and dosing profiles make them especially attractive in busy clinical environments, and emerging data suggest they may soon rival or surpass older classes in treating both skin and joint manifestations. As evidence continues to evolve, these factors play a central role in shaping early and individualized treatment strategies.

Experts discuss how treatment decisions in psoriatic arthritis increasingly balance current disease severity with long-term risk, highlighting the structural protection offered by TNF and IL-17 inhibitors, the growing preference for IL-17s in dermatology due to rapid efficacy and skin clearance, and the rising use of IL-23 inhibitors for their favorable safety, dosing convenience, and emerging joint efficacy—factors that are shaping more personalized and proactive therapeutic strategies.

Catherine J. Bakewell, MD

Articles