What’s New in Psoriatic Arthritis?

CHICAGO—Results from nearly 200 studies being conducted on psoriatic arthritis (PsA) were presented at ACR Convergence 2025. What research on PsA has the greatest potential to make a positive impact on clinical care or treatment options, or serve as the basis for future research? That’s the question The Rheumatologist asked me to explore. So I scoured the abstracts and posters presented at the annual meeting. Below, you’ll find highlights from the research on PsA presented this year, with comments on why I think it has the potential to affect how we care for our patients.

Read on.

1. Anti-PAD2 Autoantibodies
Orbai et al., Abstract 0529¹

A PsA diagnosis is frequently considered for a patient with polyarthritis who is seronegative, signifying the absence of either rheumatoid factors (RFs) or antibodies to citrullinated proteins (ACPAs or anti-CCP). Although seronegativity could suggest a mechanism other than autoimmunity, studies on patients with psoriasis (PsO) and PsA have demonstrated both B and T cell autoreactivity to a molecule known as LL37; LL37 is an anti-microbial peptide that is a member of the cathelicidin family. Further, sera of patients with PsA show antibody reactivity to post-translationally modified (PTM) forms of LL37. These PTMs include citrullination and carbamylation; the production of antibodies to PTMs is a characteristic of rheumatoid arthritis (RA). Citrullination is mediated by enzymes known as peptidylarginine deiminases (PADs), with the PAD2 enzyme effective in citrullinating LL37.

In this study, Orbai et al. used an enzyme-linked immunosorbent assay (ELISA) to determine the presence of anti-PAD2 antibodies in sera of 200 patients with PsA, as well as 75 controls. As the data indicated, 29% of PsA sera showed antibody reactivity to PDA2 compared with 9.3% of controls. In this population, anti-PAD2 antibodies were associated with more active joint disease and less active skin disease.

Although the role of autoantibodies in clinical manifestations of PsA will require further evaluation, studies such as this are important in identifying more decisively the presence of autoimmunity in PsA and showing that PsA is not actually “seronegative.” Further, the findings suggest a mechanistic link between RA and PsA because antibodies to PAD enzymes are present in both conditions. An interesting question is why an enzyme responsible for citrullination becomes a target autoantigen.

2. Risk of IBD with IL-17 Inhibitors
Tskitishvili et al., Abstract 1183²

The treatment of PsA now involves a diverse array of conventional, biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). The biologic agents include antibodies to cytokines, such as tumor necrosis factor (TNF), interleukin (IL) 17, IL-23 and IL-12/23; biologics also include abatacept, which blocks T cell co-stimulation. Although the efficacy of anti-cytokine agents appears similar, these agents may differ in potential side effects. In particular, studies have suggested that agents that target IL-17 may be associated with either a new onset of inflammatory bowel disease (IBD) or exacerbation of pre-existing disease. In this study, Tskitishvili et al. investigated this association of IL-17 inhibition and IBD by performing a retrospective observational analysis of a large cohort of patients from the TriNetX research network. TriNetX has information on more than 130 million patients from around the world, providing a rich source of data for these investigations.

Because this study involves retrospective data from real-world practices, determining an association depends on propensity score matching, an analytic approach that allows comparison of similar patient populations in terms of demographic and clinical features. Using this approach, the investigative team studied 8,931 patients in two groups differing in the use of anti-IL-17 agents.

The data indicated that those patients treated with an anti-IL-17 agent had a slightly lower risk of developing Crohn’s disease than the comparator population, but the risk for developing ulcerative colitis was significantly lower.

These findings are notable and provide valuable information to consider when prescribing biological therapies for PsA. Further, they may involve rethinking the role of certain cytokines in the pathogenesis of different inflammatory diseases and the idea that an anti-cytokine can improve one condition at the same time it provokes or worsens another.

3. Obesity & PsA Treatment Response
Mehta et al. Abstract 2691³

Classically, immune-mediated diseases, such as inflammatory arthritis, have been associated with weight loss, likely reflecting the metabolic effects of cytokines. TNF is the prime example of such a cytokine because it was originally described on the basis of its effects on weight loss (cachexia) and called cachectin. When the molecular structures of cytokines were determined, amino acid sequence analysis showed that cachectin was, in fact, the same cytokine as tumor necrosis factor, so named because of its ability to kill tumors in model systems. Despite the propensity of inflammation to cause weight loss, clinical studies have indicated that obesity and being overweight are common among patients with PsA. In this study, Mehta and colleagues characterized clinical features of 1,291 patients with PsA and determined the influence of weight on the response to therapy.

As the data showed, a higher body mass index (BMI) was significantly associated with a lower chance of achieving minimal disease activity (MDA), with BMI related to worse outcomes in multiple subcomponents of the MDA (e.g., enthesis, tender joint count, pain but not swollen joint count). Further, BMI at the time of drug initiation was associated with a reduced chance for MDA in patients treated with a TNF inhibitor (TNFi), and the TNFi group excluding infliximab; infliximab has weight-based dosing. BMI, however, did not influence the response to other agents.

Because weight may influence the response to cytokine inhibition due to effects on pharmacokinetics, these studies are important in formulating treatment plans for patients with PsA and, most pertinently, to encourage patients to embark upon a program of weight reduction by pharmacologic or non-pharmacologic means.

4. Mortality, MACE & GLP-1 Agonists
Tsibadze et al., Abstract 0849⁴

GLP-1 receptor agonists (GLP-1 RAs) have attracted great interest because of their benefits on cardiovascular and renal outcomes in patients with type 1 diabetes; more generally, the effects on weight loss are impressive. To investigate the effects of these agents on outcomes of patients with PsA, Tsibadze and colleagues used data from a large, global, multi-center research network called TriNetX; propensity score matching was used to create patient populations for comparison. In this way, the investigative team identified 4,104 patients with PsA taking GLP-1 RAs among a much larger cohort of PsA patients. The mean age of patients on GLP-1 RAs was 55.4 +/- 11.5 years, with a female preponderance. Patients who were white were the largest group. Of the patients on GLP-1 RAs, 67.3 % were obese and or overweight while 54.7% had diabetes.

Using the matching approach, the data on 3,303 GLP-1 RA and 3,303 control PsA patients indicated that GLP-1 RA use was associated with reduced risk for ischemic heart disease, cerebrovascular disease, acute myocardial infarction and cerebral infarction, but not heart failure or death. These data are important in supporting the benefit of GLP 1-RAs in a population of patients with PsA.

The mechanisms of the effects on cardiovascular disease (CVD), however, are not fully clear. Weight loss itself is one possibility because adipose tissue is a source of cytokines that can drive inflammation in the cardiovascular system, as well as joints. Future studies will determine more completely the action of these drugs, including any direct action on the immune system.

5. Axial PsA Explored
Ritchlin et al., Abstract 1753⁵

The pathogenesis of PsA is complex because of the association with skin disease and heterogeneity of joint disease, specifically, the variable presence of axial inflammation. The basis of axial involvement, which affects about 30% of patients, is not clear but is important to understand when predicting outcomes and determining treatment.

Using the NSG-SGM3 mouse model, Ritchlin et al. treated animals with either serum or peripheral blood cells (PBMCs) of patients with PsA and inflammatory back pain and radiographic findings of MRI sacroiliitis or comparable samples from patients with PsA but without axial disease. NSG-SGM3 mice are a novel, triple transgenic strain that express three human cytokines (IL-3, GM-CSF and SCF) on an immunodeficient scid (severe combined immunodeficiency) background; the presence of the human cytokines allows better engraftment of human cells.

As results of these experiments demonstrated, mice receiving serum or PBMCs from patients with axial disease demonstrated evidence of cervical and thoracic kyphosis, bone erosion and osteoproliferation in the tail; micro-CT scans showed bone resorption and bone fusion of the sacroiliac joints and lumbar spine. Further, histopathological studies showed inflammatory infiltrates with CD3 and CD8 T cells expressing both TNF and IL-17. These findings did not occur in mice receiving sera or PBMCs from patients with PsA but without axial involvement.

Although the number of mice in this study was small, the results are striking and suggest a new way to explore the mechanisms of axial disease in patients with PsA. One wonders whether similar changes would occur in patients with axial spondylitis without psoriasis or PsA and whether the active component in sera is IgG. Whatever the outcome of future studies, the results will be very interesting.

6. From Skin-Limited Disease to Joint Involvement
Raimondo et al., Abstract 1757⁶

PsA occurs in approximately 30% of patients with PsO. While this finding suggests a strong mechanistic link between events in the skin and those in the joint, the basis for the transition of disease to skin is unknown. In this clever study, Raimondo et al. tracked skin-derived cells in a model of psoriasis based on overexpression of the cytokine IL-23 (IL23OE) in KAEDE transgenic mice. The KAEDE mice express a photoconvertible protein that undergoes a green to red color change when exposed to ultraviolet (UV) radiation. Thus, by exposing skin of the mice with psoriasis to UV light, a population of red cells is created to allow their detection in the joints of the mice by fluorescence microscopy and flow cytometry.

The results of this study show that immune cells can migrate from the skin to the joint, although their presence in the synovium did not directly correlate with the presence of arthritis. Rather, in mice with arthritis, the myeloid cells differentiated into pro-inflammatory macrophages; in the resistant mice, these cells showed an M2-like anti-inflammatory phenotype. In these differentiation pathways, CD200+ synovial fibroblasts appeared to be important in determining macrophage fate and, therefore, the onset of arthritis.

These studies have two important messages: 1) Immune cells can migrate from the skin to the joint in a skin-joint axis, and 2) synovial fibroblasts have a key role in influencing macrophage differentiation.

Because skin disease precedes joint disease in most patients, it will be interesting to determine whether the type of therapy for skin disease (i.e., topical therapy vs. DMARDs) affects the development of arthritis.

7. Sacroiliac Joint Involvement in PsA
Vladimirova et al., Abstract 0543⁷

PsA is a heterogeneous condition that varies in the pattern of joint involvement, with the presence of axial disease an important determinant of signs, symptoms and clinical outcome. Distinguishing patients with a clinical diagnosis of psoriatic arthritis (clin-PsA) from those with axial spondyloarthritis with psoriasis (axSpA + PsO) thus depends on imaging studies of the spine, with magnetic resonance imaging (MRI) of major importance.

In this study of a multi-institution cohort of patients from Europe, Vladimirova et al. assessed radiographic findings in 373 patients with clin-PsA and 208 patients with axSpA + PsO. Overall, in this population, findings of inflammatory SpA were present in 21%, structural lesions in 28% and both types of lesions in 76%. In patients with MRI evidence of axPsA, MRI findings were bilateral in 76%, with bone marrow edema, erosions and fat lesions the most common features. MRI findings of axPsA were independently associated with male sex, HLA-B27 positivity, elevated C-reactive protein (CRP) values and a clinical history of inflammatory back disease. Current pack pain, however, was not discriminatory. On the other hand, peripheral arthritis showed a negative association with the findings in the spine. Clinical findings or radiographic definition (by routine X-rays) performed as well as MRI in categorizing patients.

While illuminating the diversity of MRI findings of axPsA, these observations pose important questions on the best approach to integrating MRI studies into routine care and using patient reports of symptoms in differentiating patterns of disease involvement. Another important issue is the reliability and accuracy of MRI readings by either rheumatologists or musculoskeletal radiologists in ordinary outpatient or hospital practices. Integrating advanced imaging (i.e., MRI) into routine care will, therefore, be an important challenge for the future.

8. Incidence & Risk of Arrhythmias in Patients with PsA
Almansouri et al., Abstract 0522⁸

PsA, like other forms of inflammatory arthritis, is associated with an increased risk for cardiovascular disease (CVD), with an interplay between traditional risk factors (e.g., hypertension, diabetes) and systemic inflammation determining the overall risk. In this study, Almansouri and colleagues focused on arrhythmias as a manifestation of CVD and assessed the incidence and risk factors for tachy- and bradyarrhythmias in patients with PsA.

For this purpose, the researchers used a retrospective cohort analysis of patients followed from 1994 to 2024. Arrhythmias that were assessed include atrial tachyarrhythmias, bradyarrhythmias/pacemaker use and ventricular tachyarrthymias, including placement of implantable cardioverter-defibrillator devices. The cumulative incidence rate (CIR) of each arrhythmia was calculated, taking into account age, sex, PsA duration, cardiovascular risk factors and PsA therapies. Among the 1,670 patients studied, by age 70, the overall CIRs were 7.82%, 0.45% and 0.67% for atrial-, brady- and ventricular arrythmias. Importantly, remission/low disease activity was associated with a lower risk for atrial tachyarrhythmias, while a high score on a 3-item visual analog scale (3-VAS) was associated with a higher risk for atrial tachyarrhythmias. The risk was greater in older individuals.

These findings are important in emphasizing the close relationship between inflammatory arthritis and CVD manifestations and, therefore, the need to control inflammation. In the future, studies are required to determine the effects of different therapies for PsA. In this regard, orchestrating the care of patients will likely benefit from a team approach to encompass best practices for managing traditional CVD risk factors, as well as inflammatory arthritis.

9. The Effects of JAKs on Bone Mineral Density
Wiebe et al., Abstract 0343⁹

An important consequence of inflammatory arthritis is bone loss, which can occur both locally in the joint as erosions and systemically as skeletal bone loss; this bone loss reflects a complex interplay of the effects of inflammation, treatment (especially glucocorticoids) and decreased physical activity from pain from either active or chronic disease. Although PsA and rheumatoid arthritis (RA) show some differences in pathogenesis and demographic factors (e.g., male-female frequency), they are often treated with the same agents. The study by Wiebe et al. explored the effects of JAK inhibitors on measures of bone health in a population of 856 PsA and RA patients. The study involved dual X-ray absorptiometry (DXA) for bone mineral density; a trabecular bone score (TBS); and 3D structural parameters of the femur.

The average age of the patients studied was 65 years and 77% were female. In this population, osteoporosis was present in 24% of patients, but the majority had either normal bone density or osteopenia. Interestingly, although treatment with JAK inhibitors was not associated with T-scores, vertebral trabecular micro-architecture (indicated by the TBS), showed a positive association with JAK inhibitor use, suggesting a benefit on bone micro-architecture.

This study is important in elucidating the effects on bone health that can occur with broad inhibition of cytokine signaling by JAK inhibitors. Future studies should hopefully determine whether the effects on bone health vary with the specificity of JAK inhibitors and whether there are differences among the ever-increasing array of drugs, both biologic and non-biologic, to treat PsA. 

10. Combatting Brain Fog
Mikolajczak et al., Abstract 1421¹⁰

Like many inflammatory diseases, PsA is associated with such symptoms as fatigue, mood disturbances and cognitive dysfunction (i.e., brain fog) that are an important source of morbidity and a determinant of treatment response and clinical outcome. PsA is a painful condition, and it also involves cosmesis because of the presence of skin disease, which can contribute to depression and other symptoms that track with neuropsychologic findings.

A study by Mikolajczak and colleagues found that 10.2% of patients with PsA reported subjective cognitive decline or brain fog, as determined by patient reports of problems with thinking, confusion, memory disturbance and forgetfulness. The frequency was 3% in patients with minimal disease activity (MDA) and 16% in those not in MDA. Those with subjective cognitive decline also had more comorbidities, including fibromyalgia, fatigue, anxiety and depression.

This study supports data from other rheumatic disease populations in demonstrating the impact of systemic inflammatory disease on neuropsychologic function; such effects may be a manifestation of so-called neuroinflammation. In the clinical context, these findings are important in promoting a more global treatment approach based on pharmacologic and non-pharmacologic therapies. Given the clinical complexity of such symptoms as brain fog, use of adjunctive psychological testing may be useful in defining symptomatology.

11. Perimenopause & Disease Activity
Eder et al., Abstract 1714¹¹

The influence of male-female differences on the signs and symptoms of inflammatory arthritis has long been a subject of great interest in rheumatology, especially because many rheumatic diseases are female predominant. Usually, studies assess differences between men and women on various disease features or biomarkers, although some studies divide the female population into pre- and postmenopausal groups. The situation is more complicated, however, because the perimenopausal period may have its own biology in terms of endocrinologic and immunologic changes.

In this study, Eder and colleagues analyzed 477 patients over a mean of 12.1 years. Interestingly, only 1.5% of patients received hormone replacement therapy at any time. As the data indicated, a rise in the DAPSA (Disease Activity in PsA) score was found during the perimenopausal years. Higher tender and swollen joint counts also occurred in the perimenopausal period compared with both pre- and postmenopausal periods.

These are important observations with implications for both pathogenesis and management. Although effects of sex hormones on immune responses have long been studied, future research should explore more precisely the array of hormones and their downstream effects during the interval before and after menopause. With respect to management, a key issue relates to role of hormonal replacement. This is always a complicated issue but these findings suggest it is worth another look.

12. Identifying Patients with Early PsA
Martin et al., Abstract 0107¹²

Enthesopathy is a prominent feature of PsA, but often difficult to assess clinically. As suggested by data in this study, elastography (EL) may provide a useful way to evaluate more decisively disease-related changes in the Achilles tendon. EL is an imaging technique that can determine the response of a tendon to mechanical force that may result from changes in the elastic properties of tendon structures from inflammation or damage.

As reported by Martin and colleagues, the study team performed Achilles elastography (EL-AQ) in 57 PsA patients with or without Achilles tendon involvement using ultrasound before and after controlled exercise (20 minutes on a stationary bicycle at medium resistance). As a measure of tendon properties, the MASEI (Madrid Sonographic Enthesis Score) was calculated.

The results showed the EL-AQ can discriminate between patients and controls and that changes can occur with or without clinical Achilles tendon involvement.

These are interesting findings that extend the usual use of ultrasonography to assess changes in the mechanical properties of tendons; future studies will be needed to determine the extent to which these changes reflect inflammation and, therefore, may be modified by therapy.

David S. Pisetsky, MD, PhD, is a professor of medicine and integrative immunobiology at Duke University School of Medicine, Durham, N.C., and a staff rheumatologist at the Durham VA Medical Center. He also served as the first physician editor of The Rheumatologist.

References

1. Orbai A, Wang H, Grecu M, et al. Anti-peptidylarginine deiminase-2 (anti-PAD2) autoantibodies in psoriatic arthritis [abstract 0529]. Arthritis Rheumatol. 2025;77(suppl 9).
2. Tskitishvili R, Hussein A, Tskhakaia I, et al. Risk of inflammatory bowel disease in psoriatic arthritis patients treated with IL-17 inhibitors [abstract 1183]. Arthritis Rheumatol. 2025;77(suppl 9).
3. Mehta P, Yang M, Carrizo Abarza V, et al. Understanding the impact of overweight and obesity on treatment response in psoriatic arthritis: Results from a longitudinal cohort study [abstract 2691]. Arthritis Rheumatol. 2025;7(suppl 9).
4. Tsibadze N, Tskhakaia I, Tan I. Mortality and major adverse cardiac events (MACE) with GLP-1 receptor agonists in psoriatic arthritis [abstract 0849]. Arthritis Rheumatol. 2025;7(suppl 9).
5. Ritchlin C, Rangel-Moreno J, Rangel-Garcia A, et al. Axial psoriatic arthritis is phenocopied in a humanized mouse model [abstract 1753]. Arthritis Rheumatol. 2025;7(suppl 9).
6. Raimondo M, Mohammadian H, Angeli M, et al. Skin-to-joint immune cell migration and synovial reprogramming in psoriatic arthritis onset [abstract 1757]. Arthritis Rheumatol. 2025;7(suppl 9).
7. Vladimirova N, Hadsbjerg A, Krabbe S, et al. Unveiling sacroiliac joint involvement in psoriatic arthritis: MRI, radiographic, and clinical insights from 581 European routine care patients [abstract 0543]. Arthritis Rheumatol. 2025;7(suppl 9).
8. Almansouri A, Li J, Alhadri A, et al. The incidence rate and risk factors of arrhythmias in patients with psoriatic arthritis [abstract 0522]. Arthritis Rheumatol. 2025;7(suppl 9).
9. Wiebe E, Huscher D, Boyadzhieva Z, et al. Impact of Janus Kinase inhibitors on bone mineral density and microarchitecture in rheumatoid and psoriatic arthritis: Insights from a real-world cohort [abstract 0343]. Arthritis Rheumatol. 2025;7(suppl 9).
10. Mikolajczak L, Kuhn H, Harrold L, Reed G. Impact of psoriatic arthritis disease activity and fatigue on subjective cognitive decline (‘brainfog’) [abstract 1421]. Arthritis Rheumatol. 2025;7(suppl 9).
11. Eder L, Li X, Koppikar S, et al. The perimenopause period is associated with increased levels of disease activity in psoriatic arthritis [abstract  1714]. Arthritis Rheumatol. 2025;77(suppl 9).
12. Martin Martin I, San Jose Mendez C, Jimenez Barrios S, et al. Role of achilles elastography in differentiating patients with early psoriatic arthritis [abstract 0107]. Arthritis Rheumatol. 2025;7(suppl 9).