Four-year effectiveness, safety and drug retention rate of secukinumab in psoriatic arthritis: a real-life Italian multicenter cohort.

OBJECTIVES: to evaluate over a 48-month follow-up period the: 1) long-term effectiveness and safety; 2) drug retention rate (DRR); 3) impact of comorbidities and bDMARDs line on MDA and DAPSA remission/low disease activity (LDA) of secukinumab in a multicenter Italian cohort of PsA patients. METHODS: Consecutive PsA patients receiving secukinumab were followed prospectively in Italian centers between 2016 and 2023. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were recorded. Treatment response was evaluated at 6 and 12 months after initiation, and every year up to 48 months (T48). DRR was assessed according to clinical and demographic features, comorbidities and bDMARDs line. Adverse events (AE) were recorded. RESULTS: Six hundred eighty-five patients [42.5% male] were enrolled; 32.9% naïve received secukinumab; 74.2% had ≥ 1 comorbidity. Overall, secukinumab yielded improved outcomes at T48: naïve maintained lower disease activity vs. non-naïve [DAPSA 4.0 (1.4-8.1) vs. 6.0 (2.2-10.4);p = 0.04]; 76.9% naïve and 66.2% non-naïve achieved MDA; MDA no comorbidities vs. 1-3 comorbidities 78.8% vs. 73.3% (p < 0.05), and MDA no comorbidities vs. > 3 comorbidities 78.8% vs. 48.7% (p < 0.001). DAPSA-REM and DAPSA-LDA rates were higher in naïve patients, albeit similar between those without comorbidities vs. 1-3 comorbidities, and slightly lower in those with > 3 comorbidities. Treatment was discontinued in 233 patients due to loss of effectiveness, and in 41 due to AE. The overall DRR at T48 was 66%, with differences according to bDMARDs line (p < 0.001), use of combined csDMARDs (p = 0.016), BMI (p = 0.037) and mono/oligoarthritis vs. polyarthritis (p = 0.012). CONCLUSIONS: Secukinumab proved safe and effective, and patients achieved sustained remission with a notable drug retention rate at 4 years.

Neutrophil exhaustion and impaired functionality in psoriatic arthritis patients.

Background: Neutrophils (polymorphonuclear leukocytes, PMNs) are the most abundant subtype of white blood cells and are among the main actors in the inflammatory response. Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting both the axial and peripheral joints. Typically associated with psoriasis, PsA can also affect multiple systems and organs, including the nails and entheses. Despite the involvement of PMNs in PsA, their specific role in the disease remains poorly understood. This study aimed to characterize the biological functions of PMNs and neutrophil-related mediators in PsA patients. Materials and methods: 31 PsA patients and 22 healthy controls (HCs) were prospectively recruited. PMNs were isolated from peripheral blood and subjected to in vitro stimulation with lipopolysaccharide (LPS), N-Formylmethionyl-leucyl-phenylalanine (fMLP), tumor necrosis factor (TNF), phorbol 12-myristate 13-acetate (PMA), or control medium. Highly purified peripheral blood PMNs (>99%) were evaluated for activation status, reactive oxygen species (ROS) production, phagocytic activity, granular enzyme and neutrophil extracellular traps (NETs) release. Serum levels of matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO), TNF, interleukin 23 (IL-23), and interleukin 17 (IL-17) were measured by ELISA. Serum Citrullinated histone H3 (CitH3) was measured as a NET biomarker. Results: Activated PMNs from PsA patients displayed reduced activation, decreased ROS production, and impaired phagocytic activity upon stimulation with TNF, compared to HCs. PMNs from PsA patients also displayed reduced granular enzyme (MPO) and NET release. Serum analyses revealed elevated levels of MMP-9, MPO, TNF, IL-23, IL-17, and CitH3 in PsA patients compared to HCs. Serum CitH3 levels positively correlated with MPO and TNF concentrations, and IL-17 concentrations were positively correlated with IL-23 levels in PsA patients. These findings indicate that PMNs from PsA patients show reduced in vitro activation and function, and an increased presence of neutrophil-derived mediators (MMP-9, MPO, TNF, IL-23, IL-17, and CitH3) in their serum. Conclusions: Taken together, our findings suggest that PMNs from PsA patients exhibit an "exhausted" phenotype, highlighting their plasticity and multifaceted roles in PsA pathophysiology.

Bimekizumab provided rapid improvements in patient-reported symptoms and health-related quality of life in patients with active psoriatic arthritis: pooled 16-week results from two phase 3 studies.

OBJECTIVES: To assess impact of bimekizumab treatment on patient-reported outcomes and health-related quality of life (HRQoL) in patients with active psoriatic arthritis (PsA), using 16-week data from two phase 3 studies. METHODS: BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug (bDMARD)-naïve) and BE COMPLETE (NCT03896581; tumour necrosis factor inhibitor inadequate response/intolerance (TNFi-IR)) are phase 3 studies of subcutaneous bimekizumab 160 mg Q4W; both were double-blind and placebo-controlled to 16 weeks. Patients were randomised 3:2:1 to bimekizumab, placebo or reference (subcutaneous adalimumab 40 mg Q2W) in BE OPTIMAL; 2:1 to bimekizumab or placebo in BE COMPLETE. Patient-reported outcomes for pain, fatigue, physical function and HRQoL are reported to week 16 using pooled and individual study data for bimekizumab and placebo patients. RESULTS: 1073/1112 (96.5%) patients completed week 16 (bimekizumab:| 677/698 [97.0%]; placebo: 396/414 [95.7%]). Bimekizumab-treated patients achieved rapid improvements vs placebo in pain, fatigue, physical function and HRQoL by week 4, after a single dose. Improvements continued to week 16 for all patient-reported outcomes, including Pain Visual Analogue Scale (VAS; mean (95% CI) change from baseline: bimekizumab: -|25.2 [-27.2, -23.1]; placebo:| -|5.7 [-8.2, -3.3]) and FACIT-Fatigue (bimekizumab: 4.5 [3.9, 5.1]; placebo: 1.1 [0.3, 2.0]); both nominal p<0.001. Greater proportions of bimekizumab-treated patients achieved minimal clinically important differences for patient-reported symptoms vs placebo, including FACIT-Fatigue (bimekizumab: 53.1%; placebo: 36.3%) and HAQ-DI (bimekizumab:| 53.0%; placebo: 28.7%); both nominal p<0.001. CONCLUSION: Bimekizumab treatment demonstrated rapid and greater improvements in patient-reported pain, fatigue, physical function and HRQoL to week 16 vs placebo in bDMARD-naïve and TNFi-IR patients. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT03895203; NCT03896581.

Pain catastrophizing negatively impacts drug retention rate in patients with Psoriatic Arthritis and axial Spondyloarthritis: results from a 2-years perspective multicenter GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica) study.

BACKGROUND: Chronic pain and inflammation are common features of rheumatic conditions such as Psoriatic Arthritis (PsA) and Axial Spondyloarthritis (axSpA), often needing prolonged medication treatment for effective management. Maintaining drug retention is essential for both achieving disease control and improving patients' quality of life. This study investigates the influence of pain catastrophizing, a psychological response to pain, on the drug retention rates of PsA and axSpA patients. METHODS: A two-year prospective multicenter observational study involved 135 PsA and 71 axSpA patients. Pain Catastrophizing Scale (PCS) was employed to assess pain catastrophizing. Univariable and multivariable regression analyses were utilized to identify factors associated with drug retention. RESULTS: In the PsA group, patients early discontinuing therapy showed higher baseline disease activity as well as higher incidence of comorbid fibromyalgia. Notably, pain catastrophizing, specifically the domains of Helplessness, Magnification, and Rumination, were significantly elevated in PsA patients who interrupted the treatment. Multivariable analysis confirmed pain catastrophizing as an independent predictor of drug suspension within two years. In axSpA, drug discontinuation was associated with female gender, shorter disease duration, higher baseline disease activity as well as elevated levels of pain catastrophizing. Univariable analysis supported the role of pain catastrophizing, including its domains, as predictors of treatment interruption. However, limited events in axSpA patients precluded a multivariate analysis. CONCLUSION: This prospective study emphasizes the impact of pain catastrophizing on drug retention in patients with PsA and axSpA.

Prevalence and Incidence of Psoriatic Arthritis among Patients with Psoriasis and Risk Factors for Psoriatic Arthritis in Republic of Korea: A Nationwide Database Cohort Study.

Population-based epidemiological studies on disease burden and risk factors for psoriatic arthritis (PsA) in patients with psoriasis (PsO) are limited, especially in Asian populations. Therefore, the aim was to determine the prevalence and incidence of PsA among PsO patients in Korea, and examine associated clinical factors. A cohort study was performed to determine the annual prevalence and incidence of PsA among PsO patients between 2008 and 2020 using nationwide claims data in Korea. Risk factors for PsA development were also examined using logistic regression among matched PsA cases and controls. An increasing trend in PsA prevalence per 1,000 patients was observed; prevalence was 6.17 (95% confidence interval [CI] 5.73-6.65) in 2008 and 19.03 (95% CI 18.39-19.70) in 2020. Similarly, the PsA incidence rate per 1,000 patient-years increased from 3.35 (95% CI 3.01-3.72) in 2008 to 5.01 (95% CI 4.68-5.36) in 2020. Patients with plaque PsO, moderate-to severe PsO, receiving oral systemic therapy or phototherapy, with a higher burden of comorbidities, and concomitant autoimmune diseases had a higher risk of PsA. The results provide insight into the burden of PsA among PsO patients in Korea and risk factors associated with developing PsA.

Coccidiomycosis septic arthritis presenting as ankle monoarthritis in a patient with presumed psoriatic arthritis.

A man in his 50s with a history of psoriasis was evaluated for acute on chronic left ankle pain. His symptoms were attributed to psoriatic arthritis, and he tried several immunosuppressive regimens without improvement. Further diagnostic workup confirmed Coccidioides immitis/posadasii septic monarthritis thought secondary to a known remote history of Valley fever while residing in Arizona and subsequent reactivation in the setting of immunosuppression. The patient ultimately required prolonged anti-fungal therapy and multiple surgical debridements.Although psoriatic arthritis can present as monarthritis, it is uncommon, with more likely differential considerations including crystal arthropathies, trauma and both typical and atypical infections. Acute monarthritis should always prompt concern for a septic joint, even in a patient with autoimmune disease. The specific history elicited from the patient, including residence in an endemic region, and known prior Coccidioides infection, increased suspicion for Coccidioides and led to the correct diagnosis and management.

Sacroiliac and spine imaging in spondyloarthritis: Does phenotype or sex matter?

BACKGROUND: Spondyloarthritis (SpA) encompasses a spectrum of immune-mediated inflammatory conditions primarily affecting the axial skeleton, including sacroiliitis and spondylitis, each with distinct features. This study aimed to investigate imaging disparities, focusing on sacroiliac magnetic resonance and spine radiography, across phenotypes and between males and females in axial SpA. METHOD: A cross-sectional study was conducted to assess clinical data, laboratory findings, magnetic resonance imaging (MRI) scores of sacroiliac joints using the Spondyloarthritis Research Consortium of Canada (SPARCC) and Sacroiliac Joint Structural Score (SSS), and cervical and lumbar spine radiographs utilizing the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The study aimed to compare these parameters between two groups: axial spondyloarthritis (axSpA, radiographic and non-radiographic) and axial psoriatic arthritis (axPsA), as well as between males and females. RESULTS: Ninety-four patients were included, with 62 patients in the axSpA group and 32 patients in the axPsA group. There were no differences in disease activity, mobility, radiographic damage in the spine (Modified Stoke Ankylosing Spondylitis Spine Score- mSASSS), or sacroiliac magnetic resonance imaging (MRI) scores (Spondyloarthritis Research Consortium of Canada Magnetic Resonance Imaging Index - SPARCC and Sacroiliac Joint Structural Score - SSS) between the two phenotypes. Regarding sex, in imaging exams, men had higher mSASSS (p = 0.008), SSS (p = 0.001), and fat metaplasia (MG) score based on SSS (p = 0.001), while women had significantly higher SPARCC scores (p = 0.039). In the male group, the presence of HLA-B27 allele had an impact on more structural lesions on MRI (SSS), p = 0.013. CONCLUSION: In this study, imaging of sacroiliac joints and spine in patients with axial SpA did not show differences in phenotypes but did reveal differences based on sex, which may have an impact on future diagnostic recommendations. Further studies are needed to confirm these findings.

Tuberculin skin test repetition after TNF-α inhibitors in patients with chronic inflammatory arthritis: a long-term retrospective cohort in endemic area.

OBJECTIVES: To evaluate the tuberculin skin test (TST) conversion in chronic inflammatory arthropathies (CIA) patients on TNFα inhibitors (TNFi) and without previous latent tuberculosis infection (LTBI) treatment. METHODS: Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with negative LTBI were retrospectively evaluated for TST conversion and active tuberculosis (TB) after six months of exposition to TNFi. Two groups were compared: patients who repeated TST (TST-repetition) during the follow-up and patients who did not (non-TST-repetition). RESULTS: A total of 355 CIA patients on TNFi were screened and 138 (38.9%) did not fulfill the inclusion criteria. Of the remaining 217 CIA patients, 81 (37.3%) repeated TST during TNFi treatment. TST conversion rate was observed in 18 (22.2%) patients without significant differences among CIA (p = 0.578). The number of TB cases was low (n = 10; 4.6%) and was similar in TST-repetition and non-TST-repetition groups [2 (2.5%) vs. 8 (5.9%), p = 0.328]. Of note, 30% of active TB occurred early (6-12 months of TNFi exposure) and the median (full range) time to incident TB was 1.3 (0.6-10.6) years, whereas the median (full range) time to TST repetition was later [3.3 (0.5-13.4) years]. The incidence of active TB was lower among RA patients than AS patients [342 (95% CI 41 - 1446) vs. 1.454 (95% CI 594-2993)/100,000 patient-years, p = 0.049]. CONCLUSION: These results indicate that TST repetition is associated with a high conversion rate, suggesting the need for recommended treatment. The delayed repetition of TST and low number of active TB cases hampered the evaluation of this strategy effectiveness to prevent active infection. Larger studies with systematic repetition patterns are necessary. In addition, the study highlights the need for a greater surveillance for TB in AS patients.

Gender differences in clinical features and quality of life of patients with axial spondyloarthritis and psoriatic arthritis.

OBJECTIVE: The aim of the current study was to compare the clinical and treatment characteristics and dimensions of health-related quality of life between female and male patients with axial spondyloarthritis (SpA) and psoriatic arthritis (PsA). METHODS: The present study is cross-sectional and comprises 119 patients with axial SpA and 198 patients with PsA. Clinical data were collected by standardized and self-reported instruments. Disease activity was evaluated by the Ankylosing Spondylitis Disease Activity Score with C-reactive protein and the Disease Activity in PSoriatic Arthritis (for SpA and PsA, respectively). Health-related quality of life was assessed with the Medical Outcomes Study 36-item Short Form Survey. Patients were stratified by gender, and the socio-demographic, clinical, and quality-of-life data were compared. RESULTS: Women with axial SpA and PsA had significantly lower education (p<0.001, p=0.004, respectively) and higher disease activity (p<0.001, p=0.003, respectively). Female patients with axial SpA were more frequently under second-line therapy (p=0.026) and glucocorticoid treatment (p=0.005), while women with PsA had more radiographic progression (p=0.006). Female patients with axial SpA and PsA had worse scores in the dimensions of quality of life regarding physical role, bodily pain, vitality, and mental health. Women with axial SpA had lower scores in general health, while women with PsA had lower scores in physical and social functioning. CONCLUSIONS: Women with axial SpA and PsA had worse scores than men in most clinical and treatment characteristics and health-related quality of life dimensions.

Treatment of spondyloarthritis with disease-modifying anti-rheumatic drugs during pregnancy and breastfeeding: comparing the recommendations and guidelines of the principal societies of rheumatology.

OBJECTIVE: This paper aims to provide an overview of the use of treatments available for axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) during pregnancy and breastfeeding, according to current national recommendations and international guidelines, as well as data on the impact on pregnancy outcomes of paternal exposure to treatment. METHODS: We performed a narrative review of national and international recommendations and guidelines on the reproductive health of patients suffering from rheumatic diseases. The last updated recommendations and guidelines were considered source data. RESULTS: We reported updated information regarding the treatment of axSpA and PsA with nonsteroidal anti-inflammatory drugs, intra-articular glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and targeted synthetic DMARDs during the preconception period, pregnancy, and breastfeeding, as well as data related to paternal exposure. We highlighted any medications that should be discontinued and/or not used in the reproductive age group and also treatments that may be continued, avoiding the withdrawal of drugs that can be used in the different phases, thus preventing the risk of increasing disease activity and flares before, during, and after pregnancy in SpA patients. CONCLUSIONS: The best management of pregnancy in patients with SpA is based on knowledge of updated drug recommendations, a careful and wise evaluation of the risks/benefits of starting or continuing treatment from the SpA diagnosis in a woman of childbearing age through pregnancy and lactation, and sharing therapeutic choices with other healthcare providers (in particular, gynecologists/obstetricians) and the patient.

Psoriasis in women with psoriatic arthritis: hormonal effects, fertility, and considerations for management at different stages of life.

OBJECTIVE: This review examines skin manifestations in women with spondyloarthritis, with a particular focus on psoriatic arthritis (PsA) and associated psoriasis. METHODS: A narrative review of the bibliography was conducted using the main databases (PubMed, Scopus, EMBASE). RESULTS: The review showed that the clinical course of PsA and psoriasis in women is influenced by hormonal fluctuations that occur at different stages of life, such as menstruation, pregnancy, postpartum, and menopause. Gender differences in the epidemiology of PsA and psoriasis are discussed and attributed to biological, hormonal, and environmental differences. The role of estrogen in modulating immune responses and its impact on the severity of PsA and psoriasis are reviewed. Special emphasis is placed on the psychosocial impact of visible skin lesions on women's quality of life and fertility problems associated with psoriasis. Treatment strategies are also taken into account, favoring personalized approaches that consider the safety of treatments during pregnancy and breastfeeding. CONCLUSIONS: The review highlights the importance of a holistic and gender-sensitive approach to the management of PsA and psoriasis in women, promoting the integration of physical treatment with support for emotional well-being.

Sex and gender differences in comorbidities in spondyloarthritis: a focus on psoriatic arthritis.

OBJECTIVE: Spondyloarthritis is a family of inflammatory diseases subdivided into those affecting the spine, called axial spondyloarthritis, and those involving peripheral joints, such as psoriatic arthritis (PsA). Several studies have reported differences in clinical manifestations, outcomes, and treatment responses between male and female PsA patients. The aim of our review was to evaluate if differences may also be identified in the context of cardiovascular (CV) risk factors and diseases. METHODS: Patients with PsA have a higher CV risk than the general population. The increased CV risk associated with PsA is likely caused by the complex interplay of traditional CV risk factors, chronic systemic inflammation, and side effects related to the use of certain anti-rheumatic drugs. RESULTS: Sex differences in CV risk factors in PsA patients, according to several studies, are controversial. However, the few studies that reported sex-stratified estimates did not find differences in the risk of stroke and myocardial infarction between sexes. The same also holds true for CV mortality. These mixed results may be related to the different study designs and case definitions, as well as genetic and geographical variability across the investigated populations. CONCLUSIONS: In conclusion, our review suggests that the evaluation of sex-gender aspects of CV comorbidities in PsA should be a central step in the context of personalized medicine in order to prevent and treat properly associated comorbidities.

Upadacitinib to improve anxiety in patients with adalimumab-treated psoriatic arthritis: study protocol for a randomized controlled trial.

BACKGROUND: Patients with psoriatic arthritis (PsA) often suffer from anxiety disorders. While upadacitinib has shown effectiveness in reducing various disease activity indicators in active PsA, its impact on anxiety disorders in PsA patients needs further investigation. METHODS: In this 12-week randomized, open-label, controlled trial, PsA patients with coexisting anxiety were randomly assigned to either the upadacitinib group or the adalimumab group in a 1:1 ratio. The upadacitinib group received a daily dose of 15 mg, while the adalimumab group received 40 mg every 2 weeks. The primary outcome measured the change in Hospital Anxiety Self-Assessment Scale (HADS-A) total scores after the 12-week intervention. Secondary outcomes included changes in the Health Assessment Questionnaire-Disability Index (HAQ-DI), the percentage of participants meeting the ACR20 criteria compared to baseline after 12 weeks, and the percentage of participants achieving a grade 0 or 1 in the psoriasis static Investigator's overall assessment (sPGA) at week 12 with an improvement of at least 2 points from baseline (sPGA 0/1). One-way analysis of variance (ANOVA) was used to compare the means of normally distributed variables between the upadacitinib and adalimumab groups. DISCUSSION: The impact of upadacitinib on anxiety in PsA patients remains uncertain. This 12-week open randomized controlled trial aims to provide insights into disease progression and underscore the importance of addressing PsA-related anxiety during treatment. TRIAL REGISTRATION: ChiCTR2400079755. Registered on January 11, 2024, with ChiCTR. https://www.chictr.org.cn/showproj.html?proj=216538.

Development of a questionnaire to assess the patient perspective regarding challenges in psoriatic arthritis treatment-a mixed-methods study.

BACKGROUND: Limited data exist on psoriatic arthritis (PsA) treatment in lower-income regions, particularly from the patient perspective. This study explores the challenges faced by socioeconomically vulnerable PsA patients and the reasons for non-adherence to treatment guidelines. The main objective of the study is to develop a questionnaire to identify the primary challenges in PsA treatment adherence and to analyze its feasibility while simultaneously understanding the target population's unique characteristics. METHODS: We included PsA patients meeting the Classification Criteria for PsA (CASPAR), excluding those with other overlapping inflammatory diseases. The study, supported by two patient-research partners, began with focus groups to identify treatment challenges, leading to the creation of a 26-item questionnaire. Its reliability was verified using the test-retest method, targeting a percent agreement ≥ 0.8. Then, PsA patients at a rheumatology clinic completed the final survey. RESULTS: The study involved 69 PsA patients. The final questionnaire contained 26-questions across five-domains, with a 92.2% agreement rate and an average completion time of 8.3 minutes. Diagnostic delays exceeded a year for 59% of patients and more than two years for 33%. Daily life disruptions affected 43.2% of patients, with 35.3% taking sick leave or retiring. Around 25% waited over 8 weeks for drug approval, and 17.6% required legal intervention to access medication. Drug dispensation issues impacted about 60% of patients. Furthermore, 66.7% lived far from their rheumatologist, with 49% traveling over an hour for appointments. Approximately 30% were unaware of the risks of methotrexatein relation to alcohol consumption and pregnancy. CONCLUSIONS: The questionnaire was feasible and reliable, with its results underscoring patient-centric challenges in PsA management, particularly concerning diagnostic delays and medication access, as well as daily life disruptions and misinformation. These findings emphasize the urgency for healthcare reforms aimed at improving diagnosis efficiency, patient education, and streamlined medication access, emphasizing the need for tailored initiatives to improve the healthcare experience for PsA patients.

Differential immunological profiles in seronegative versus seropositive rheumatoid arthritis: Th17/Treg dysregulation and IL-4.

Background: Rheumatoid arthritis (RA) is an autoimmune disease with various subtypes. Among these, seronegative rheumatoid arthritis (SnRA), distinguished by its distinctive seronegative antibody phenotype, presents clinical diagnosis and treatment challenges. This study aims to juxtapose the immunological features of SnRA with seropositive rheumatoid arthritis (SpRA) to investigate potential mechanisms contributing to differences in antibody production. Methods: This study included 120 patients diagnosed with RA and 78 patients diagnosed with psoriatic arthritis (PsA), comprising 41 cases of SnRA and 79 cases of SpRA. Clinical, serological, and immune data were collected from all participants to systematically identify and confirm the most pivotal immunological distinctions between SnRA and SpRA. Results: (1) SpRA demonstrates more pronounced T-helper 17 cells (Th17)/Regulatory T cells (Treg) dysregulation, vital immunological differences from SnRA. (2) SpRA exhibits higher inflammatory cytokine levels than SnRA and PsA. (3) Lymphocyte subset ratios and cytokine overall distribution in SnRA close to PsA. (4) Interleukin-4 (IL-4) emerges as the central immunological disparity marker between SnRA and SpRA. Conclusion: Th17/Treg imbalance is one of the vital immunological disparities between SnRA and SpRA. Interestingly, PsA and SnRA display similar peripheral blood immunological profiles, providing immunological evidence for these two diseases' clinical and pathological similarities. Furthermore, IL-4 emerges as the central immunological disparity marker between SnRA and SpRA, suggesting its potential role as a triggering mechanism for differential antibody production.

Impact of Central Sensitization on Clinical and Functional Aspects of Psoriatic Arthritis.

Background/Objectives: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease characterized by peripheral arthritis, enthesitis, spondylitis and psoriasis. The objective of this study was to examine the prevalence of central sensitization (CS) and its impact on the clinical and functional aspects of PsA. Methods: Adult patients with PsA according to the Classification of Psoriatic Arthritis (CASPAR) criteria were included in this cross-sectional observational study. The Central Sensitization Inventory (CSI) was used to assess the presence of CS. The study evaluated the impact of CS on individuals by analyzing many factors including demographic information, laboratory findings, clinical features, disease activity, quality of life, severity of sleeplessness, frequency of depression and anxiety. The patients were categorized into distinct groups based on the existence and intensity of CS, and a comparative analysis was conducted on their respective outcomes. Results: A total of 103 PsA patients with a mean age of 43.2 (SD: 6.7) years and including 42 (40.8%) males were included. The mean CSI score was 45.4 (SD: 15.1), and 67 (65.1%) patients had CS. The logistic regression analysis revealed that the variables Psoriasis Area Severity Index (PASI), General Anxiety Disorder-7 (GAD-7), and Insomnia Severity Index (ISI) exhibit considerable predictive power in relation to the outcome variable CS (p < 0.05). PASI was observed as the most important variable in predicting CS (OR 9.70 95% CI: 1.52-62.21). Conclusions: CS has demonstrable efficacy in influencing laboratory, clinical, and functional markers among individuals with PsA. When assessing pain sensitivity in these patients, it is important to take into account the presence of CS.

Comparative early effectiveness across 14 PsA drugs and 5 classes of PsA treatment: 3-month results from the PRO-SPIRIT study.

BACKGROUND: The psoriatic arthritis (PsA) Observational Study of Persistence of Treatment (PRO-SPIRIT) assesses effectiveness and persistence of real-world PsA treatments. Ixekizumab (IXE) is an interleukin (IL)-17A inhibitor (i) (IL-17Ai), approved for the treatment of adult PsA. METHODS: The aim of this predefined interim analysis was to report baseline characteristics along with early (3-month) descriptive and comparative real-world effectiveness in patients with PsA prescribed with advanced treatment including IL-17Ai; IXE or secukinumab (SEC), IL-12/23i, IL-23i, tumour necrosis factor (TNFi) or Janus kinase (JAKi). RESULTS: 1192 patients across 6 countries were analysed. At baseline, patients receiving IXE had longer disease duration and higher previous biological/targeted-synthetic disease-modifying antirheumatic drugs experience than patients starting TNFi and SEC 150, and less concomitant conventional-synthetic DMARD use than TNFi and JAKi. Comparative analyses at 3 months showed that: (a) versus TNFi, IXE exhibited similar improvement in clinical Disease Activity in PsA (cDAPSA) but significantly greater improvement in body surface area affected by psoriasis (BSA) and global assessments (physician GA, patient GA (PatGA)); (b) versus IL-12/23i and IL-23i (pooled), IXE showed significantly greater improvement in cDAPSA and PatGA; (c) IXE was as fast as JAKi in improving joint disease activity. Ad hoc analysis indicated that more patients with active psoriasis (BSA ≥3%) achieved minimal disease activity with IXE than JAKi or IL-12/23i. The responses to SEC varied by dosage. CONCLUSIONS: This study confirms the rapid 3-month effectiveness of IXE on joint disease activity-as fast as TNFi and JAKi (cDAPSA), and exceeding IL-12/23i and IL-23i-along with clear benefits to skin.

Ultrasound nail assessment in patients with psoriasic arthritis: is there an association of findings with clinical scores?

BACKGROUND: Psoriatic arthritis can involve several domains. Due to its multifaceted nature and its frequent comorbidities such as depression, obesity, osteoarthritis and fibromyalgia, it is difficult to monitor these patients because the clinical scores involve subjective data. High-resolution ultrasound probes allowed the evaluation of more superficial structures, such as the nails and their synovio-entheseal framework, in close relationship with the enthesis of the distal extensor digitorum tendon. Nail ultrasound studies vary in terms of the parameters and fingers studied and in their findings. OBJECTIVES: To describe the most significant sonographic nail changes and the most affected fingers in psoriatic arthritis and to verify the association of nail ultrasound findings with clinical scores (nail psoriasis severity index (NAPSI), ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP), minimal disease activity (MDA), disease activity index for psoriatic arthritis (DAPSA)). METHODS: This was a cross-sectional study with 52 patients with psoriatic arthritis at the Hospital de Clínicas do Paraná and 50 controls. A total of 1016 nails were analyzed (517 from patients with psoriatic arthritis and 499 from controls). Ultrasonography of the nails of the 10 fingers was performed to assess the trilaminar appearance, measure the distance from the nail bed, identify synovitis of the distal interphalangeal joints and the presence of a power Doppler signal from the nail matrix/nail bed. The captured images were independently evaluated by a rheumatologist with expertise in musculoskeletal ultrasound. Data analysis was performed using IBM SPSS Statistics v.28.0.0 software, and the association of nail plate changes, nail bed distance and power Doppler signal with the NAPSI, DAPSA, MDA and ASDAS-PCR were calculated. Spearman correlation coefficients were estimated to analyze the correlations between pairs of quantitative variables. Student's t test and the Mann‒Whitney U test were used to compare quantitative variables, and Fisher's exact test was used to compare categorical variables between patients and controls. The nonparametric Mann‒Whitney U and Kruskal‒Wallis tests were used to compare groups according to the MDA or DAPSA classification. RESULTS: The Doppler signal of the nail matrix and nail bed was more frequently identified in patients (44.2%) than in controls (6%), and the difference in the mean power Doppler signal between the two groups was significant (p < 0.001). Changes in the nail plate were more common in the right thumb (44.2%), left thumb (36.5%) and second finger on the right hand (32.7%). The number of fingers with nail plate changes, enthesitis, paratendinitis, grayscale synovitis and DIP involvement in the distal interphalangeal joints was higher among patients with psoriatic arthritis (p < 0.001). There were found some correlations between US findings and clinical scores: ultrasound nail involvement and the NAPSI score (p = 0.034), the number of fingers and mean change in the nail plate and the ASDAS-CRP (p = 0.030). DAPSA (remission/low activity versus moderate/high activity) was associated to the mean change in the nail plate (p < 0.013). CONCLUSIONS: Nail ultrasound has the potential to assist in the capturing of the actual disease activity status in patients with psoriatic arthritis.

Impact of initiation of targeted therapy on the use of psoriatic arthritis-related treatments and healthcare consumption: a cohort study of 9793 patients from the French health insurance database (SNDS).

OBJECTIVES: To assess the potential impact of targeted therapies for psoriatic arthritis (PsA) on symptomatic treatments (non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, opioid analgesics), methotrexate and mood disorder treatments and on hospitalisation and sick leave. METHODS: Using the French health insurance database, this nationwide cohort study included adults with PsA who were new users (not in the year before the index date) of targeted therapies for ≥9 months during 2015-2021. Main endpoints were difference in proportion of users of associated treatments, hospitalisations and sick leaves between 3 and 9 months after and 6 months before targeted therapy initiation. Logistic regression models adjusted for sex, age, psoriasis, inflammatory bowel disease and Charlson Comorbidity Index compared the impact of biologics initiation (tumour necrosis factor inhibitor (TNFi)/interleukin 17 inhibitor (IL17i)/IL12/23i) on associated treatment discontinuation. RESULTS: Among 9793 patients initiating targeted therapy for PsA (mean age: 51±13 years, 47% men), 62% initiated TNFi, 14% IL17i, 10% IL12/23i, 1% Janus kinase inhibitor, 12% phosphodiesterase-4 inhibitor. After treatment initiation, the proportion of treatment users was significantly reduced for NSAIDs (-15%), opioid analgesics (-9%), prednisone (-9%), methotrexate (-15%) and mood disorder treatments (-2%), along with decreased hospitalisations (-12%) and sick leaves (-4%). TNFi had a greater sparing effect on NSAIDs and prednisone use than IL17i (ORa=1.04, 95% CI=1.01 to 1.07; 1.04, 1.02 to 1.06) and IL12/23i (1.07, 1.04 to 1.10; 1.06, 1.04 to 1.09). Odds of methotrexate discontinuation was reduced with TNFi versus IL17i (0.96, 0.94 to 0.98) and IL12/23i (0.94, 0.92 to 0.97). CONCLUSIONS: Targeted therapy initiation for PsA reduced the use of associated treatment and healthcare, with TNFi having a slightly greater effect than IL17i and IL12/23i, except for methotrexate discontinuation.

Psoriatic arthritis subtypes are phenocopied in humanized mice.

Psoriatic arthritis (PsA) is a complex inflammatory disease that challenges diagnosis and complicates the rational selection of effective therapies. Although T cells are considered active effectors in psoriasis and PsA, the role of CD8+ T cells in pathogenesis is not well understood. We selected the humanized mouse model NSG-SGM3 transgenic strain to examine psoriasis and PsA endotypes. Injection of PBMCs and sera from patients with psoriasis and PsA generated parallel skin and joint phenotypes in the recipient mouse. The transfer of human circulating memory T cells was followed by migration and accumulation in the skin and synovia of these immunodeficient mice. Unexpectedly, immunoglobulins were required for recapitulation of the clinical phenotype of psoriasiform lesions and PsA domains (dactylitis, enthesitis, bone erosion). Human CD8+ T cells expressing T-bet, IL-32 and CXCL14 were detected by spatial transcriptomics in murine synovia and by immunofluorescence in the human PsA synovia. Importantly, depletion of human CD8+ T cells prevented skin and synovial inflammation in mice humanized with PsA peripheral blood cells. The humanized model of psoriasis and PsA represents a valid platform for accelerating the understanding of disease pathogenesis, improving the design of personalized therapies, and revealing psoriatic disease targets.