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Objectives: To evaluate the in vitro effect of tofacitinib on autophagy activity of psoriatic arthritis (PsA) fibroblast-like synoviocytes (FLS), and to confirm its activity on inflammatory and invasive properties of FLS and synovial cells, deepening the impact on mitochondrial function., Methods: FLS, peripheral blood mononuclear cells (PBMCs), and synovial cells from active PsA patients were cultured with tofacitinib 1 μM or vehicle control for 24 h. Autophagy was measured by Western blot and by fluorescence microscopy. Chemokines/cytokines released into culture supernatants were quantified by ELISA, while invasive properties of FLS by migration assays. Specific mitochondrial probes were adopted to measure intracellular reactive oxygen species (ROS), mitochondrial potential, morphology, turnover and mitophagy. Oxygen consumption rate (OCR), reflecting oxidative phosphorylation, was quantified using the Seahorse technology. Differences were determined by adopting the non-parametric Wilcoxon signed rank test., Results: 18 patients with moderately-to-severely active PsA were enrolled. Tofacitinib significantly increased the levels of the autophagy markers LC3-II and ATG7 in PsA FLS compared to vehicle control, suggesting an increase in spontaneous autophagy activity; no effect was highlighted in PBMCs and synovial cells cultures. Tofacitinib reduced migration properties of PsA FLS, and reduced MCP-1 and IL-6 release into FLS and synovial cells cultures supernatants. Furthermore, tofacitinib decreased intracellular ROS production, increased basal OCR, ATP production and maximal respiratory capacity, and enhanced mitophagy and mitochondrial turnover., Conclusions: The JAK inhibitor tofacitinib reduces the pro-invasive and pro-inflammatory properties of PsA FLS. Autophagy induction and mitochondrial quality control modulation by tofacitinib might contribute to FLS function restoration., Competing Interests: Declaration of competing interest ES has received research support from AbbVie and Lilly and consulting/speaker's fees from AbbVie, Galapagos, Lilly, Novartis, Astra-Zeneca and Amgen. MG has received research support from AbbVie, Pfizer and Lilly and consulting/speaker's fees from AbbVie, Galapagos, Lilly, Alfa-Sigma, Astra-Zeneca and Amgen. The other authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Inflammatory arthritis (IAs), such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), are characterized by the presence of chronic synovitis. The Krenn's synovitis score (KSS), a simple tool detectable by haematoxylin/eosin staining of synovial biopsy samples, allows the discrimination between high-grade and low-grade synovitis. The aim of this study was to identify the clinical associations of KSS and to evaluate the relationship between high-grade synovitis and treatment response in IA patients., Methods: Clinical, laboratory and ultrasound data were retrieved from RA and PsA patients recruited in the prospective MATRIX cohort study. Inclusion criteria were age≥18 years, RA or PsA diagnosis, and presence of active disease with eligibility to start/modify therapy. Patients underwent ultrasound-guided synovial biopsy of one of the most involved joints before starting/modifying treatment according to treat-to-target strategy. The samples were analysed by an expert pathologist for KSS calculation. Univariable and multivariable logistic regression analyses were performed to evaluate the relationship between KSS and baseline variables. The association between KSS and treatment response at 24 weeks of follow-up was investigated in univariable logistic regression analysis., Results: 53 patients, 34 RA and 19 PsA, completed 24 weeks of follow-up after synovial biopsy. Patients were either treatment naïve (N=6, 11%), csDMARDs-experienced (N=46, 87%) or b/tsDMARDs-experienced (N=20, 38%). Median KSS was 6.00 (Q1-Q3 4.00-7.00) in RA and 4.00 (3.00-6.00) in PsA (p=0.040), and inflammatory infiltrates score was significantly higher in RA than in PsA patients (median 3.00 vs 2.00, p=0.021). In multivariable analysis, synovial effusion in the biopsied joint (OR 9.26, 95%CI 2.12-53.91) and erythrocyte sedimentation rate (ESR) (OR 1.04, 95%CI 1.01-1.08) associated with high KSS. High-grade synovitis significantly associated with a higher probability of achieving DAS28 remission, ACR20/50 response, and Boolean2.0 remission, independently from diagnosis., Conclusion: Several markers of pro-inflammatory pathways associated with the presence of high-grade synovitis, and patients with higher KSS shared a higher probability of treatment targets achievement in the follow up. The integration of a simple and feasible tool like KSS in the clinical and prognostic stratification of patients with IA might help in intercepting patients with a disease more prone to respond to available treatment paradigms., Competing Interests: ES has received research support from AbbVie and Lilly and consulting/speaker’s fees from AbbVie, Galapagos, Lilly, Novartis, Astra-Zeneca and Amgen. MG has received research support from AbbVie, Pfizer and Lilly and consulting/speaker’s fees from AbbVie, Galapagos, Lilly, Alfa-Sigma, Astra-Zeneca and Amgen. AB has received consulting/speaker’s fees from Astra-Zeneca and GSK. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Garaffoni, Tamussin, Calciolari, Lanza, Bortoluzzi, Scirè, Govoni and Silvagni.)

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD -0.85 [95% CI -1.23; -0.47]) and CD68+ macrophages (sublining, sl) (SMD -0.74 [-1.16; -0.32]) in synovial biopsies from patients treated for 4-12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature.

Introduction: Psoriatic arthritis (PsA) occurs in 10%-15% of people with psoriasis and accounts for 10%-20% of early arthritis clinics referral. Only a few prognostic factors of therapeutic response in patients with PsA have been identified. In the last years, the role of imaging has grown up and the European League Against Rheumatism recognised that ultrasound (US) has higher sensitivity than clinical examination to detect inflammatory disease activity. The aims of the Ultrasound in PSoriatic arthritis TREAtMent (UPSTREAM) study are to integrate clinic and US in order to inform whether US has provide an added prognostic value in PsA., Methods and Analysis: UPSTREAM is an observational prospective cohort study enrolling patients with PsA having clinically active joint disease and starting a new course of therapy. The primary objective is to evaluate the additional value of US over clinical examination in detecting patients achieving minimal disease activity after 6 months. Data will be obtained at baseline and at standard clinical follow-up visits. Patient's clinical assessment will be performed according to the core set proposed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis-Outcome Measures in Rheumatology. Sonographic evaluations will be performed by expert sonographers in 42 joints, 36 tendons, 12 entheses and 2 bursae, according to a score that will be purposely developed for PsA by the US Study Group of the Italian Society for Rheumatology. The UPSTREAM study will identify clinical and US predictors of response to treatment in patients with PsA and active peripheral arthritis starting a new course of therapy., Ethics and Dissemination: Ethic approval for this study has been obtained from the institutional review board (IRB)/independent ethics committee (IEC) Comitato Etico Lazio 1 (Prot. N 198 02-02-2017) and then locally from the IRB/IEC of each participating centre. Results will be published in relevant scientific journals and be disseminated in international conferences. Fully anonymised data will be accessible from authors upon request., Trial Registration Number: NCT03330769; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Psoriatic arthritis is a systemic inflammatory disease in which enthesitis and dactylitis are two of the main hallmarks of the disease. In the last years, ultrasonography is increasingly playing a key role in the diagnosis of psoriatic arthritis and ultrasonography of the entheses, particularly of the lower limbs, is commonly used to assess patients with that disease. New advancements in ultrasound equipment using high frequencies probes allowed us also to identify and characterize the involvementof the entheses of the hand in psoriatic arthritis, confirming the results of the experimental models of the disease and the theory of the sinovial-entheseal complex, even in small joints.

Psoriatic arthritis (PsA) is characterized by chronic inflammation of peripheral joints and axial skeleton, associated with a strong genetic background. Clinics include enthesitis or dactylitis and extra-articular involvement as uveitis or inflammatory bowel disease, while treatment options range from nonsteroidal anti-inflammatory drugs (NSAIDs) to biologics, targeting TNF α or Th17. No serum autoantibody is associated with PsA, while other biomarkers have been proposed for early diagnosis or to predict treatment response. To better discuss this area of growing interest we performed a systematic review of the literature on biomarkers in PsA. Our research retrieved 408 papers, and 38 were included in the analysis. Based on the available literature, we draw some recommendations for the use of biomarkers in the management of patients with PsA.

Psoriatic arthritis (PsA) is an arthropathy associated with psoriasis, which is part of the spondyloarthropathy family, and which may present with various forms, from mono-oligoarthritis to symmetric polyarthritis mimicking rheumatoid arthritis. In longstanding disease, the symmetric polyarthritis is the most common pattern of PsA, involving the small joints of hands, feet (the involvement of which seems to be very common, ranging from 50 to 100% of patients), wrists, ankles and knees. Other common features are represented by the inflammation of enthesis and tendons. Its exact prevalence, in Italy, should be about 30% in psoriatic subjects or 0.42% when considering the general population. The aims of our study were to investigate, by US examination, the prevalence and the features of foot involvement in PsA and to describe their correlations with clinical findings. Ultrasound (US) examinations were performed using a Logiq 9 (General Electric Medical Systems, Milwaukee, WI) equipped with a multifrequency linear probe, working at 14 MHz. One hundred and eighty feet were investigated in a total of 101 patients. Prior to US assessment, all patients underwent a clinical examination by an expert rheumatologist who recorded the presence/absence of pain, tenderness (detected by palpation and/or active or passive mobilisation of the feet) and swelling. US finding indicative of metatarsophalangeal joint inflammation were obtained in 77 (76.2%) patients, while only 34 (33.7%) patients were positive to the clinical examination. This study demonstrates that US detected a higher number of inflamed joints with respect to clinical assessment in PsA patients.

Psoriatic arthritis (PsA) is an arthropathy associated to psoriasis, which is part of the spondyloarthropathy family, and which may present with various forms, from mono-oligoarthritis to symmetric polyarthritis mimicking rheumatoid arthritis. In longstanding disease, the symmetric polyarthritis is the most common pattern of PsA, involving small joint of hands, feet, wrists, ankles and, very frequently, knees. Other common features are represented by the inflammation of enthesis and tendons. Ultrasound (US) examinations were performed using a Logiq 9 (General Electric Medical Systems, Milwaukee, WI) equipped with a multifrequency linear probe, working at 10-14 MHz. One-hundred and sixty-six knee joints were investigated in a total of 83 patients. Prior to US assessment, all patients underwent a clinical examination by an expert rheumatologist who recorded the presence/absence of pain, tenderness (detected by palpation and/or active or passive mobilisation of the knee), and knee swelling. Sixty-two (74.7%) knee joints were found clinically involved, while at least one US finding indicative of joint inflammation was obtained in 70 (84.3%) knee joints. In the 59% of the patients we noticed synovial hypertrophy. Enthesitis was present in 39.7% of the subjects studied. This study demonstrated that US detected a higher number of inflamed knee joints and enthesis with respect to clinical assessment in PsA patients.

Objective: To determine the presence and clinical significance of antibodies to cyclic citrullinated peptides (anti-CCP) in psoriatic arthritis (PsA)., Methods: We performed a cross-sectional study on 102 outpatients (56 men) with PsA consecutively recruited from a tertiary referral center. Median disease duration was 36 months (interquartile range 21-81). All patients were investigated for peripheral joint and axial involvement, enthesitis, and dactylitis. Laboratory investigations included anti-CCP, assessed by enzyme-linked immunosorbent assay and IgM rheumatoid factor (RF). Plain radiographs of pelvis, wrists, hands, and feet were performed in all cases., Results: Anti-CCP were detected in 16/102 patients, 8/68 with symmetric polyarthritis, 1/8 with asymmetric polyarthritis, 2/20 with mono-oligoarthritis, 1/2 with mutilating arthritis, and 0/4 with exclusive axial or distal interphalangeal (DIP) involvement. The male:female ratio as well as frequency of dactylitis, enthesitis, and nonexclusive axial or DIP joint involvement were similar in the anti-CCP positive and negative groups. Anti-CCP positive patients were more frequently treated with disease modifying antirheumatic drugs and showed higher number of involved joints, and higher frequency of erosive arthritis and positive RF. Using multiple logistic regression, anti-CCP (but not RF) were significantly associated with erosive arthritis (odds ratio 9.8; 95% confidence interval 1.87-51.8) and > or = 10 involved joints (17.99; 3.6-89.2)., Conclusion: Anti-CCP can be found in a small but significant proportion of patients with a clinical picture of PsA and are associated with erosive arthritis and multiple joint involvement.