Dr. Pisetsky, a professor of medicine and immunology at Duke University School of Medicine and a staff rheumatologist at the Durham VA Medical Center, both in Durham, N.C., has curated the research abstracts and posters and gives us his take on the most important research on psoriatic arthritis being presented at the annual meeting.
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WASHINGTON, D.C.—In this report, we identify important research on psoriatic arthritis (PsA) presented at ACR Convergence 2024, summarize the abstracts and comment on why each is important, addressing the relevance for clinicians and the potential impact on future research.
1. Sex-Related Differences
Abstract 0588: Coates et al.1
Although rheumatic conditions share many features in common (e.g., inflammatory arthritis), they nevertheless differ in the role of sex on the frequency and severity of disease, an important issue for both disease management and investigation into pathogenesis. In contrast to rheumatoid arthritis (RA) and systemic lupus erythematosus, with a prevalence among women, PsA shows more similar rates among men and women. Real-world experience suggests some relevant clinical differences in clinical manifestations and disease outcome. To elucidate these differences, Coates et al. analyzed baseline characteristics of patients in three phase 3, randomized clinical trials for guselkumab, an inhibitor of interleukin 23 (IL-23).
The results of this analysis indicated that female patients have less severe psoriasis, a longer duration of PsA and a greater impact on quality of life than male patients. Other differences included more frequent enthesitis in women, although dactylitis was more common among men. Women also reported more fatigue.
The basis of these differences is not clear although they suggest the impact of sex on various manifestations of immune-mediated disease perhaps related to the respective roles of autoimmunity and inflammation in pathogenesis. PsA and psoriatic skin disease (PsO), for example, are not characterized by autoantibody production.
It is of interest in this regard that glucocorticoid use among patients in these studies was low (approximately 20% in women and 16% in men); in contrast, a trial of a new agent in RA would likely show about 50% of patients use glucocorticoids. Although speculative, these considerations could point to the differential role of hormones in the spectrum of diseases encompassed in rheumatology.
2. Are Self-Reports of the Extent of Psoriasis & Dactylitis Valid?
Abstract 1671: Nielung et al.2
In clinical evaluations in healthcare settings, the patient usually provides the history of their symptoms and their chronology, and the physician determines the physical findings in a more objective way. The traditional approach may change in the future; however, as indicated by a study from Denmark concerning a national registry system called DANBIO. This system incorporates patient-reported outcome measures (PROMs) that are completed by patients online prior to consultation with the physician.
In this study, the PROMs were extended to include non-musculoskeletal manifestations, including dactylitis, skin and nail psoriasis and uveitis, as reported by patients with PsA. These are all physical findings, the usual province of the physician. The patient reports were compared with those of the physicians. Following the initial experience with this registry, the question on dactylitis was modified to include a photo of a patient foot to illustrate “sausage toes.” The incorporation of the photo boosted agreement of patient and physician assessments.
The agreement between patients and physicians on skin psoriasis and nail psoriasis was also good, although uveitis was uncommon in the overall patient population.
These findings are important because they suggest that patient self-reports can be useful in assessing and monitoring key manifestations of PsA in the real-world setting and can facilitate communication and care. For manifestations of psoriasis, either skin or joint, the physical findings can be readily appreciated. It will be of interest to know whether this approach can be extended to other rheumatic conditions in which the physical findings can be more subtle or nuanced.
3. Fibromyalgia with PsA
Abstract 1229: Maroof et al.3
PsA is a chronic disabling inflammatory arthritis that can be associated with fibromyalgia (FM), another source of chronic pain. As now defined, FM is a form of nociplastic pain that differs from nociceptive pain triggered by noxious stimuli or neuropathic pain from nerve injury. In FM, central sensitization can amplify pain; this amplification can lead to allodynia and hyperalgesia and can thereby complicate assessment of disease activity and its severity.
The etiology of FM is complex and can result from stress, trauma and other psychosocial factors; socioeconomic factors can also be drivers of this condition. In delineating the origin and impact of FM, determining its occurrence in different racial and ethnic populations as well as different countries can be informative. The study by Maroof et al. assessed FM in 554 PsA patients from Arab League of Associations of Rheumatology (ArLAR) countries using questionnaires and patient-reported outcomes (PROs).
As indicated by the data, FM can be found in about 20% of patients with PsA and is associated with higher disease activity and worse quality of life. The 20% frequency is similar to that found in other rheumatic diseases and far greater than the general population; these findings suggest some common mechanisms, possibly related to inflammation or the other effects of chronic illness. The impact of cultural factors is not yet clear although more observations from different countries and regions could provide insights.
Certainly, the findings suggest the importance in routine care of a more comprehensive evaluation for FM in patients with PsA; this evaluation could involve validated screening tools similar to those used in this study. In the trial setting, assessing the impact of therapies on FM symptoms could provide unique information that could be applied to other rheumatic diseases.
4. Cigarette Smoking & Radiographic Progression
Abstract 1436: Kharouf et al.4
Smoking has so many adverse health effects that an association with worse outcomes in PsA would not be unexpected especially because smoking has been linked to greater radiologic damage in RA. Kharouf et al. therefore investigated a large population of patients with PsA in a prospective, observational cohort assessing a number of clinical variables in non-smokers, past smokers and current smokers. The results indicated that a shortened time to progression of radiographic joint damage occurred with older age, shorter duration of psoriasis, baseline swollen joint joints, baseline dactylitis and an abnormal erythrocyte sedimentation rate.
Interestingly, current smokers showed less progression of peripheral joint damage. Smoking is part of the, so-called, exposome that represents the environmental influences to which an individual is exposed. Constituents of the exposome can impact on immunological process, showing both pro-inflammatory and anti-inflammatory effects. Among other diseases, studies have indicated that smoking may protect against ulcerative colitis (UC) in contrast to Crohn’s disease. The effect of smoking on UC has been variously attributed to the action of nicotine and carbon monoxide, although many other mechanisms, including epigenetic changes, are possible.
Although much research is needed to disentangle the effects of smoking, nevertheless, this study provides intriguing clues to the ways in which environmental exposures can affect disease—with differential effects on PsA and RA, providing further evidence for the distinct pathophysiologies of these conditions.
5. Calcium Pyrophosphate Deposition Disease & PsA
Abstract 2311: Anumolu et al.5
The diagnosis of PsA is not always straightforward, even in patients with psoriasis because PsA can coexist with osteoarthritis (OA) and RA. In the absence of a definitive biomarker, the diagnosis of PsA is clinical. The study by Anumolu et al. explores the relationship between calcium pyrophosphate deposition disease (CPPD) and PsA using a large patient cohort from the Veteran Affairs database, comparing CPPD patients with a matched population of controls.
The data indicate that the proportion of CPPD patients with PsA was double that of the controls and that more CPPD patients were diagnosed with psoriasis than controls. In about 62% of patients, the diagnosis of PsA preceded that of CPPD by at least a year.
These findings raise interesting questions about the interplay between inflammatory and degenerative disease, including the role of trauma in pathogenesis. These findings also have impact clinically in assessing the respective roles of PsA and CPPD in driving symptomatology, with ongoing crystal-induced arthropathy perhaps accounting for treatment resistance among some patients with PsA.
6. Fragility Fracture
Abstract 1451: Amin et al.6
PsA and RA are systemic inflammatory diseases with articular and extra-articular manifestations. Although both are marked by polyarthritis, PsA and RA nevertheless show notable differences, including the male-female ratio, and management options include the range of approved biologic therapies. Another difference concerns the use of glucocorticoids, with generally lower usage in PsA than RA.
Amin and Bukhari addressed another potential difference between these conditions and investigated issues of bone health and the occurrence of fragility fractures. This issue has been well analyzed with RA (including the role of glucocorticoid-induced osteoporosis [GIOP]), but the data on PsA are much more limited.
This study, which analyzed a group of 233 PsA patients who had been referred for dual-energy X-ray absorptiometry (DXA) scanning, made interesting observations including a lack of association with traditional risk factors with fractures and the occurrence of fracture at lower bone mineral density (BMD) than expected. In addition, the frequency of femoral fractures among PsA patients in this study was low; most of the fractures were vertebral.
Although the study is limited by patient numbers and risk of referral bias, nevertheless, the findings are important in sorting out the basis of bone loss in patients with inflammatory arthritis and the relative contributions of inflammation and GIOP; decreased mobility is another factor to consider. Future studies will be important in assessing the effects of the ever-increasing number of therapies for PsA on this common and often serious comorbidity.
7. Placebo Response Rates
Abstract 0772: Kerschbaumer et al.7
The treatment of PsA has shown rapid advances in the past two decades with the development of both biologic and targeted synthetic DMARDs. The regulatory approval of these agents has been based on the conduct of large randomized, controlled trials (RCT) using state-of-the-art outcome measures. Although RCTs are key to evidence-based medicine, they are nevertheless subject to variation with evolution of therapy and the expansion of clinical sites into less affluent countries to assure adequate recruitment.
As demonstrated by Kerschbaumer et al., the changes in recruitment patterns, most notably the geographic shift to less affluent countries, has had a significant impact on the placebo (PBO) response in PsA trials over the years. Thus, PBO responses have increased among trials with start dates from 1996–2019. In addition to this trend, the PBO response showed a strong negative correlation with the gross national income. Although the basis of these changes is not fully known, the likely explanation relates to prior therapy of the enrolled patients and their access of healthcare coupled with the regression of the mean.
The increase in PBO response has important implications for trial design and evaluation of the efficacy of any new agent, as well as comparison with previously approved therapies.
8. Effect of Systemic Immunosuppressive Therapies on Cardiovascular Risk
Abstract 0141: Esmaeili et al.8
PsA, like other forms of inflammatory arthritis, is associated with an increased prevalence of atherosclerotic cardiovascular disease (ASCVD), likely reflecting the impact of systemic inflammation on the vasculature. The frequency of ASCVD events, however, may be modifiable by the use of immunosuppressive agents, although the risk of heart failure may also occur with certain agents.
To assess these effects, Esmaeili et al. analyzed a retrospective cohort in Veterans Administration hospitals in Southern California, comparing patients with PsA with matched controls. Among patients on methotrexate or tumor necrosis factor inhibitor (TNFi) monotherapy, the risk of cardiovascular events was higher than controls, although treatment with Th17 inhibitors (Th17i targeting IL-17 or IL-12/23) showed lower rates. Other analyses showed a lower risk of cardiovascular accidents with biologic agents but the risk of heart failure was slightly reduced with TNF1 or unchanged or increased with Th17i.
This study is important in demonstrating the increased risk of cardiovascular events in patients with PsA and indicating the potential of biologic therapies in attenuating this risk; the effects on heart failure, however, remain unclear. Although this study prompts the need for more extensive evaluation of the effects of current and new agents on ASCVD risk, it also suggests that effects of therapy on the heart and the vascular system may differ depending on cytokine or pathway targeted. In this context, the term biologic may be too encompassing to allow distinction of relevant differences among agents.
9. Diagnostic Ultrasound Enthesitis Tool (DUET) for PsA
Abstract 0851: Eder et al.9
In addition to joint involvement, enthesitis is a key feature of PsA, although clinical assessment of the involvement of the entheses can be challenging. To determine the utility of ultrasound (US), Eder and colleagues from 17 centers evaluated a new PsA-specific sonographic scoring system for detecting enthesitis at multiple sites. The US protocol entailed 16 entheseal sites in the upper and lower extremities, with abnormalities scored on a semi-quantitative scale for inflammatory and structural lesions. The study included 213 patients with PsA and 106 controls.
The results indicated that the prevalence of inflammatory lesions was generally higher in PsA patients, although the frequency varied by entheseal site. Power Doppler signals were found to be infrequent and also dependent on site. Although other differences between patients and controls were observed for specific lesions assessed, the overall conclusion of the study is that sonographic entheseal abnormalities are not exclusive to PsA. These findings suggest that the US for evaluating entheses may need to take into account both the entheseal site affected as well as the severity of the findings. Future studies will be needed to determine how best to incorporate US in comprehensive evaluation of PsA by imaging.
10. Active Hand Inflammation
Abstract 0227: Ramirez et al.10
In evaluating patients with inflammatory polyarthritis, the distinction between PsA and RA can usually be readily accomplished because of psoriatic skin disease (PsO) for patients with PsA, and anti-citrullinated protein antibodies (ACPAs) for those with RA. Nevertheless, imaging is a valuable tool to understand disease pathogenesis as well as develop information for prediction and treatment response. Ramirez et al. used ultrasound to assess finding of proliferative synovitis (PS) in PsA and RA patients with hand involvement, focusing on synovial hypertrophy (SH) and Power Doppler (PD) in patients with seropositive RA, seronegative RA and PsA.
In this population, approximately one-half of patients met criteria for PS on ultrasound, with the frequency greater in seropositive RA than either seronegative RA or PsA. PS was associated with erosions in these patients. On the other hand, tendon involvement was observed in all groups and interestingly 12% of patients had tendon involvement without joint involvement. Finger ankyloses occurred rarely in this patient cohort and was found only in those with PsA, highlighting another difference between PsA and other forms of inflammatory polyarthritis.
Although this study concerned ultrasound findings, an interesting aspect relates to medication use, with 25% of patients with PsA on glucocorticoids that were associated with erosion; this association may be related to their use in patients with more severe disease. Although therapy with glucocorticoids in RA is well established (although controversial), their effects on disease in PsA merit attention, with imaging providing novel information to determine their impact on joint and tendon involvement in PsA.
David S. Pisetsky, MD, PhD, is a professor of medicine and immunology 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
- Coates L, Selmi C, Mease P, et al. Sex-related differences in baseline patient and disease characteristics: Post hoc analyses of three phase 3, randomized, double-blind, placebo-controlled studies in patients with active psoriatic arthritis [abstract]. Arthritis Rheumatol. 2024;76(suppl 9).
- Nielung L, Hetland M, Skov L, et al. Are patient-reported outcomes for dactylitis, uveitis, psoriatic skin and nail disease valid in patients with psoriatic arthritis? [abstract]. Arthritis Rheumatol. 2024;76(suppl 9).
- Maroof A, Ziade N, El Kibbi L, et al. Frequency of fibromyalgia using validated measures in a sample of patients with psoriatic arthritis and impact on disease: A cross-sectional multinational study [abstract]. Arthritis Rheumatol. 2024;76(suppl 9).
- Kharouf F, Maldonado Ficco H, Gao S, et al. The association of cigarette smoking with radiographic progression in psoriatic arthritis [abstract]. Arthritis Rheumatol. 2024;76(suppl 9).
- Anumolu N, Rosenthal A, Sherman K, Singla S. Higher rates of psoriatic arthritis in patients with calcium pyrophosphate deposition disease than controls: A retrospective cohort study in US veterans [abstract]. Arthritis Rheumatol. 2024;76(suppl 9).
- Amin H, Bukhari M. Predictors and patterns of fragility fracture in an observational cohort of patients with psoriatic arthritis [abstract]. Arthritis Rheumatol. 2024;76(suppl 9).
- Kerschbaumer A, Steiner M, Khalili S, et al. Global recruiting patterns are associated with placebo response rates in clinical trials of psoriatic arthritis [abstract]. Arthritis Rheumatol. 2024;76(suppl 9).
- Esmaeili M, Truong L, Ridolfi N, et al. The effect of systemic immunosuppressive therapies on cardiovascular risk in psoriatic arthritis patients [abstract]. Arthritis Rheumatol. 2024;76(suppl 9).
- Eder L, Acayaba de Toledo R, Afgani F, et al. Diagnostic ultrasound enthesitis tool (DUET) for psoriatic arthritis: The distribution of elementary lesions is influenced by site [abstract]. Arthritis Rheumatol. 2024;76(suppl 9).
- Ramírez J, Torrente-Segarra V, Cuervo A, et al. Active hand inflammation: Differing clinical and ultrasound patterns in patients with rheumatoid arthritis and psoriatic arthritis. A cross-sectional and multicenter study [abstract]. Arthritis Rheumatol. 2024;76(suppl 9).
