Inflammation In Psoriatic Arthritis Research Articles

Serum Calprotectin as an Inflammatory Marker in a Cohort of Egyptian Patients with Psoriatic Arthritis and its Correlation with Disease Activity and Radiological Findings

Abstract Background Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and is found in about 20 to 30% of psoriatic patients. The use of inflammatory markers can be disappointing in PsA, since they are elevated in only half of the patients with PsA., in this study we assessed serum calprotectin as a marker of inflammation in psoriatic arthritis and correlated it to disease activity and radiological findings. Objective To measure serum calprotectin level in psoriatic arthritis patients and to assess its association with disease activity score and radiological findings using musculoskeletal ultrasound. Methods This was a Case-Control Study Rheumatology inpatient departments and outpatient clinics at Ain Shams University Hospitals. This study was conducted on 50 patients with psoriatic arthritis according to the classification criteria for psoriatic arthritis (CASPAR) criteria and 30 Normal subjects with no past medical history and with no family history of psoriasis. Results Patients serum calprotectin level had statistically significant higher value in comparison to the control group P-Value < 0.001., and with cutoff point 106.36 ng/ml with sensitivity 98% and specificity of 86.6 %, There was highly statistically significant relation between the level of serum calprotectin and synovial hypertrophy in small hand joints P-Value=0.004 and it can predict synovial hypertrophy in hands by joint ultrasound at the level of 258.9 ng/ml with sensitivity and specificity of 71%, 83% respectively There was also a with statistically significant relation nail bed affection in ultrasound P-Value=0.034. Multiple regression analysis was done in psoriatic arthritis patients and it was found that serum calprotectin was the most predictive for the presence of psoriatic arthritis in comparison to ESR and CRP. Conclusion in psoriatic arthritis patients, serum calprotectin level is significantly higher and is correlated to radiographic and nail changes. Further studies are required to define a specific cutoff serum level for diagnosis.

Multimodal Imaging of Structural Damage and Inflammation in Psoriatic Arthritis: A comparison of DMARD-Naive and DMARD-Failure Patients.

To compare inflammatory and structural differences in active Psoriatic Arthritis (PsA) between disease-modifying antirheumatic drug (DMARD)-naive and DMARD-failure patients using diverse imaging approaches for future analyses. Additionally, to explore the influence of patient characteristics (clinical and demographic variables) on imaging findings. Of the 80 patients included from the first cohort of the ongoing multicentre TOFA-PREDICT trial, 40 were DMARD-naive and 40 were DMARD-failure (csDMARD failure; 1 prior bDMARD excluding etanercept was allowed), all meeting classification criteria for PsA with a minimum disease duration of eight weeks. Baseline conventional radiographs of hands and feet, MRIs of both ankles, and whole-body 18F-FDG PET/CT were evaluated for inflammatory and structural imaging parameters, including Sharp-van der Heijde (SHS), Heel Enthesitis Magnetic Resonance Imaging Scoring System (HEMRIS) and Deauville synovitis scoring. Differences between groups and the influence of patient characteristics were examined with multiple linear regression. At baseline, patient characteristics were similar between groups. Imaging parameters showed limited inflammation and structural damage. Inflammatory imaging parameters were not significantly different (p> 0.200). Among structural parameters, only HEMRIS Achilles tendon structural damage was significantly different (p= 0.024, R2=0.071) and, SHS Joint Space Narrowing was not statistically significant (p= 0.050, R2=0.048) with higher values for both in DMARD-failures. After correction of patient characteristics, these differences in imaging disappeared (both p> 0.600). At baseline, PsA patient groups were comparable concerning structural and inflammatory imaging parameters, especially after correcting for patient characteristics. Thus, DMARD-naive and DMARD-failure patient groups may be combined in future PsA progression and treatment decision studies. EudraCT: 2017-003900-28.

Impact of blue-collar vs. white-collar occupations on disease burden in psoriatic arthritis patients: A Swiss clinical quality management in rheumatic diseases cohort study

Biomechanical stress may exacerbate inflammation in psoriatic arthritis (PsA). This study aimed to investigate disease activity, work disability, and drug response/retention rates in PsA patients among two different occupation’s types: blue-collar workers (BCol) with manual labor versus white-collar workers (WCol) with sedentary occupations. PsA patients registered in the Swiss cohort (SCQM) were classified as BCol or WCol workers and assessed at the initiation of a biologic or targeted synthetic disease-modifying anti-rheumatic drug (b-/tsDMARD). We compared the baseline characteristics at treatment start and the DAS28-CRP for the 1-year remission. Treatment retention was investigated using Kaplan–Meier curves and Cox regression analysis. Multivariable models were adjusted for potential confounders. Of 564 patients, 29% were BCol, and 71% were WCol workers. Baseline disease activity was comparable between both groups. BCol workers were predominantly male (79.8%) and more work disabled at baseline (84.0% vs. 27.9%; p < 0.01). One hundred seventy-four treatment courses (TCs) of 165 PsA patients were included for longitudinal analysis. Occupation did not significantly influence the achievement of DAS28-CRP remission at 1 year. Kaplan–Meier analysis (n = 671) indicated longer retention for BCol workers (mean retention duration: 3.15 years vs. 2.15 years, (p = 0.006). However, adjusted Cox regression analysis did not corroborate these findings. This study indicates that physically demanding occupations correlate with increased rates of work disability among PsA patients, while treatment response seems to be unaffected by the patients’ occupation type. Additional research is required to thoroughly comprehend the relationship between physical workload, disease activity, and treatment outcomes.Key Points• This study indicates that physically demanding occupations correlate with increased rates of work disability among PsA patients.• The treatment response among of PsA patients seems unaffected by the patients’ occupation type.

Determinants of radiographic progression in early psoriatic arthritis: insights from a real-world cohort

ObjectivePersistent articular inflammation in psoriatic arthritis (PsA) is associated with radiographic damage. Despite advances in diagnosis and therapy, radiographic structural damage remains prevalent in PsA. To elucidate this topic, we...

Increased Circulating CD14+ Monocytes in Patients with Psoriatic Arthritis Presenting Impaired Apoptosis Activity.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis primarily affecting peripheral and axial joints. The osteolytic effect in the damaged joint is mediated by osteoclast activation. We aimed to investigate differential gene expression in peripheral CD14+ monocytes between patients with psoriatic arthritis (n = 15) and healthy controls (HCs; n = 15). Circulating CD14+ monocytes were isolated from peripheral blood mononuclear cells using CD14+ magnetic beads. Cell apoptosis was measured via Annexin V using flow cytometry. The gene expression profiling was analyzed via microarray (available in the NCBI GEO database; accession number GSE261765), and the candidate genes were validated using PCR. The results showed a higher number of peripheral CD14+ monocytes in patients with PsA than in the HCs. By analyzing the microarray data, identifying the differentially expressed genes, and conducting pathway enrichment analysis, we found that the apoptosis signaling pathway in CD14+ cells was significantly impaired in patients with PsA compared to the HCs. Among the candidate genes in the apoptotic signaling pathway, the relative expression level of cathepsin L was confirmed to be significantly lower in the PsAs than in the HCs. We concluded that the numbers of peripheral CD14+ monocytes increased, and their apoptosis activity was impaired in patients with PsA, which could lead to enhanced macrophage maturation and osteoclast activation. The resistance of apoptotic death in peripheral CD14+ monocytes may contribute to active joint inflammation in PsA.

Increased vascular inflammation on PET/CT in psoriatic arthritis patients in comparison with controls

BackgroundPatients with psoriatic arthritis (PsA) have an increased risk of cardiovascular disease, possibly due to a chronic inflammatory state.ObjectivesThe main objective of this study was to investigate the difference in...

Persistent pain and its predictors after starting anti-tumour necrosis factor therapy in psoriatic arthritis: what is the role of inflammation control?

Objective While considerable focus has been placed on pain due to inflammation in psoriatic arthritis (PsA), less is reported on pain despite inflammation control. Here, we aimed to investigate the occurrence/predictors of persistent pain, including non-inflammatory components, after starting anti-tumour necrosis factor (anti-TNF) therapy. Method Bionaïve PsA patients starting a first anti-TNF therapy 2004–2010 were identified (South Swedish Arthritis Treatment Group register; N = 351). Outcomes included unacceptable pain [visual analogue scale (VAS) pain > 40 mm], and unacceptable pain despite inflammation control (refractory pain; VAS pain > 40 mm + C-reactive protein < 10 mg/L + ≤ 1 swollen joint of 28), assessed at 0, 3, 6, and 12 months. Baseline predictors were estimated by logistic regression. Results Upon starting anti-TNF therapy, 85% of patients reported unacceptable pain, falling to 43% at 3 months and then remaining stable. After 12 months, refractory pain constituted 63% of all unacceptable pain. Higher baseline VAS pain/global, worse physical function and lower health-related quality-of-life were associated with a higher risk of unacceptable/refractory pain at 12 months. More swollen joints and higher evaluator’s global assessment were associated with a lower risk of 12-month refractory pain. Conclusions A substantial proportion of PsA patients reported unacceptable pain throughout the first anti-TNF treatment year. At 12 months, refractory pain constituted about two-thirds of this remaining pain load. More objective signs of inflammation at anti-TNF initiation were associated with less future refractory pain. This highlights insufficient effect of biologics in patients with inflammation-independent pain, warranting alternative treatments.

The dietary acid load is associated with disease severity inpsoriatic arthritis.

An acidogenic diet, by disrupting the blood pH equilibrium, can contribute to metabolic acidosis and lead to inflammation. Therefore, we hypothesized that dietary acid load (DAL) increases disease activity and inflammation in psoriatic arthritis (PsA) patients. This study was conducted with 58 obese/overweight patients, aged 20-65 years. Dietary intake was assessed using a 3-consecutive-day 24-hour recall. The DAL was evaluated through the PRAL (potential renal acid load) and NEAP (net endogenous acid production) and divided into the low and high groups by their median values. The disease activity assessments, anthropometric measurements, dietary data, and blood parameters of patients were recorded and compared at the low and high DAL groups. We observed that patients in the high NEAP and PRAL groups had worse PsA pattern scores (P < 0.05). Also, PRAL and NEAP scores were positively associated with Disease Activity Index for Psoriatic Arthritis, Health Assessment Questionnaire, and Psoriatic Arthritis Impact of Disease-12 (PSAID-12) scores. After adjusting age, sex, smoking, and body mass index, 1 mEq increase in PRAL and NEAP was associated with an elevation of Disease Activity Index for Psoriatic Arthritis (0.506 and 0.486 points, respectively). These results showed a close relationship between DAL and PsA symptoms. An acidogenic diet may negatively affect PsA prognosis. Healthy eating recommendations should be part of the management of the disease.

Changes of inflammation in patients with psoriatic arthritis after high intensity interval training assessed by ultrasound and MRI, a randomized controlled trial

BackgroundIn psoriatic arthritis (PsA) there is a theoretical risk of increased disease activity related to strenuous physical activity, including exercise. We evaluated the effect of high intensity interval training (HIIT) on objective measures of inflammation in PsA assessed by ultrasound (US) of peripheral joints and entheses, and by bone marrow edema (BME) on MRI of the sacroiliac joints (SIJ) and spine.MethodsWe randomly assigned 67 PsA patients to an intervention group that performed structured HIIT for 11 weeks, or to a control group instructed not to change their physical exercise habits. Outcome measures included US evaluation of the total cohort and MRI in a subgroup of 41; both assessed at 3 months. We calculated the proportions with an increased US B-mode and power-doppler (PD) signal of joints and entheses and Spondyloarthritis-Research-Consortium-of-Canada (SPARCC)-BME score of the SIJ and spine for both groups.ResultsProportions with an increased US B-mode score of the joints were 32% and 28% in HIIT and control groups, respectively. Corresponding proportions of PD scores of the joints were 7% and 10% and PD scores of entheses were 32% and 31%.The proportions with increased MRI BME of the SIJ were 6% in the HIIT group and 10% in the control group. Corresponding proportions were 6% and 5% for the MRI BME of the spine.ConclusionIn PsA patients with a low to moderate disease activity, there was no clear evidence of objectively measured increased inflammation after HIIT, as evaluated by US and MRI.Trial registrationClinicalTrials.gov NCT02995460 (16/12/2016).

OA16 Identification of surrogate serum proteomic biomarkers associated with ultrasound power Doppler in psoriatic arthritis

Abstract Background/Aims An area of key unmet need in psoriatic arthritis (PsA) is the identification of biomarker(s) which predict those likely to respond to a specific therapy; in order to achieve that, an objective measure of disease activity would be ideal. Ultrasound power Doppler (PD) is a semi-quantitative measure of inflammation. However, ultrasound is time-consuming and requires specific expertise, whereas a blood-based surrogate biomarker of PD would be easier to apply clinically, and could serve as an objective outcome measure of response. Our aim is to identify proteomic biomarkers associated with PD in PsA patients. Methods Twenty-six patients with PsA (fulfilling CASPAR criteria) were recruited prospectively. All underwent 66-joint ultrasound examination and presence of PD was recorded. There were 7 patients without PD(-) and 19 with PD(+) detectable in at least 1 joint. Proteomics data for 1,073 proteins were generated using sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH MS). Proteins with high levels of missing data were filtered (&amp;gt;30%) followed by random forest analysis. Differentially expressed proteins (DEPs) based on PD status were identified. Protein-protein interaction network analysis was performed using the search tool for retrieval of interacting genes (STRING), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO). Results Following pre-processing, 553 proteins were available for analysis. Seventeen DEPs were identified (p-values &amp;lt;0.05) (Table 1). Among these, ERAP2, an enzyme involved in MHC-I ligand processing and a known risk factor for inflammatory diseases, had the largest fold change (-0.64 95%CI -1.20 to -0.07, p = 0.03). Network analysis revealed that the 17 DEPs were significantly enriched (p &amp;lt; 0.001) in the PD+ group. KEGG pathway analysis identified the association of the DEPs in leukocyte transendothelial migration (strength 1.5 FDR=0.04). GO analysis of the DEPs revealed involvement in immunoglobulin receptor binding (strength 2.28 FDR=0.03). Conclusion We identified several potential serum proteomic biomarkers correlated with disease activity, as assessed by the presence of PD, in PsA; these provide insights into the biological mechanisms underlying synovitis in PsA. Validation in a larger cohort and functional studies are required to determine the role of these proteins in mediating inflammation in PsA. Disclosure R.M. Hum: None. N. Nair: None. S.F. Ling: None. A. Barton: None. P. Ho: None. D. Plant: None.

The role of trauma and isomorphic reaction in the pathogenesis of psoriatic arthritis

The role of biomechanical stress and trauma in the initiation of inflammation of the joints and periarticular structures in psoriatic arthritis (PA) is currently not fully understood. Soft tissues and joints are the target for constant biomechanical stress and microtrauma, leading to inflammation. There is an opinion that this inflammation in PA is due to an analogue of the skin isomorphic reaction that develops in the skin of psoriatic patients in response to trauma. Some authors have called this reaction the deep Koebner phenomenon. It is assumed that the early, preclinical phase of psoriatic arthritis may be based on inflammation of the enthesis as a response to microtrauma, and explained by the proximity of the entheses and the articular membranes. Detection of early changes in entheses in psoriatic patients, including those who do not have complaints from the musculoskeletal system, is of great importance for the early diagnosis of psoriatic arthritis. In the literature review, the sources for the period 20102021 were studied, devoted to the role of the isomorphic reaction and microtraumatization in the pathogenesis of PA, as well as the role of various imaging methods for the early diagnosis of enthesitis in psoriatic patients.

P276 Ixekizumab shows a pattern of pain improvement in patients with and without measurable inflammation in psoriatic arthritis

Abstract Background/Aims The efficacy of ixekizumab (IXE) and adalimumab (ADA) in patients with psoriatic arthritis (PsA) has been previously reported using ACR 50 and Psoriasis Area and Severity Index (PASI) 100 responses. To minimize confounding effects, in this analysis we assessed the efficacy of either IXE or ADA monotherapy on reduction of pain beyond measurable inflammation in patients with active PsA and low C-reactive protein (CRP) (&amp;lt;5mg/L) at baseline. Methods SPIRIT-H2H (NCT03151551) was a 52 week (W), multicenter, randomized, open-label, parallel-group, assessor-blinded study evaluating the efficacy and safety of IXE vs ADA. Participants were randomized (1:1) to approved-label dosing of IXE or ADA. This post-hoc analysis included only patients treated with IXE or ADA as monotherapy and with low CRP (&amp;lt;5mg/L) at baseline. Changes in joint pain were measured using PsA Patient’s Assessment of Pain Visual Analog Scale (VAS). We stratified patients into four categories by two measures of inflammation: 1. Sustained low inflammation either by a. CRP&amp;lt;5 mg/L during W4-24 or b. ≥50% improvement in swollen joint count (SJC) during W8-24. 2. Fluctuating inflammation either by a. CRP≥5 mg/L at least once between W4-24 or &amp;lt; 50% improvement in SJC at least once between W8-24. Results 95 monotherapy patients with a CRP &amp;lt;5mg/L at baseline were included in this analysis. Baseline characteristics were similar between both treatment arms. In patients with fluctuating inflammation as measured by CRP, IXE-treated patients demonstrated a numerically greater mean improvement in joint pain VAS vs ADA-treated patients at W16 (IXE: -31.64, ADA: -25.33) that was sustained up to W52 (IXE: -47.69, ADA: -20.67). There was significance in favor of IXE at W32 (p = 0.0045) and W52 (p = 0.0288). In patients with sustained low inflammation as measured by CRP, there was comparable improvement in joint pain between IXE and ADA-treated patients. In patients with sustained improvement in joint swelling as assessed by SJC, IXE-treated patients demonstrated a numerically greater mean improvement in joint pain VAS vs ADA-treated patients from W4 (IXE: -17.47, ADA: -10.42) that was sustained through W52 (IXE: -43.16, ADA: -32.62). In patients with fluctuating improvement in joint swelling as assessed by SJC, IXE-treated patients demonstrated a numerically greater mean improvement in joint pain VAS vs ADA-treated patients from W16 (IXE: -22.00, ADA: -19.31) that was sustained through W52 (IXE: -28.57, ADA: -13.27). Conclusion This analysis suggests a different pattern of pain improvement in patients with low baseline CRP treated with IXE or ADA monotherapy, with a favorable pain reduction outcome for IXE-treated patients, even when inflammation is fluctuating as measured by CRP or SJC improvement. This analysis supports the hypothesis that IXE improves joint pain in PsA patients with and without measurable inflammation. Disclosure N. Maney: None. K. de Vlam: Consultancies; Celgene, Eli Lilly and Company, Galapagos NV, Novartis, Pfizer, and UCB Pharma. Grants/research support; Celgene. G. Gallo: Shareholder/stock ownership; Eli Lilly and Company. P. Mease: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Galapagos NV, Gilead Sciences, GlaxoSmithKline. Member of speakers’ bureau; AbbVie, Amgen, Janssen, Novartis, Pfizer, and UCB Pharma. Grants/research support; Janssen, Merck Sharp &amp; Dohme, Neumentum, Novartis, Pfizer, Sun Pharma, and UCB Pharma. P. Rahman: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, and UCB Pharma. Grants/research support; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, and UCB Pharma. V. Krishnan: Shareholder/stock ownership; Eli Lilly and Company. D. Sandoval Calderon: Shareholder/stock ownership; Eli Lilly and Company. C. Lin: Shareholder/stock ownership; Eli Lilly and Company. D. Zhu: Shareholder/stock ownership; Eli Lilly and Company. R. Bolce: Shareholder/stock ownership; Eli Lilly and Company. P. Conaghan: Consultancies; Amgen, Bristol Myers Squibb, Eli Lilly and Company, Galapagos NV, Gilead Sciences, Novartis, Pfizer, and UCB Pharma.

P253 Ultrasound demonstrates continued improvement in psoriatic arthritis synovitis and enthesitis with secukinumab: 52-week results from a Phase 3 study

Abstract Background/Aims Power Doppler ultrasound (PDUS) is a sensitive non-invasive imaging tool to visualize a wide range of articular and periarticular inflammation in psoriatic arthritis (PsA). ULTIMATE (NCT02662985) is the first large RCT that used ultrasound with Global OMERACT ultrasound synovitis score (GLOESS) as the primary endpoint, to demonstrate early benefits of secukinumab on synovitis in patients with PsA through 12 weeks. Here we report the responsiveness of ultrasound on synovitis and enthesitis, clinical efficacy, and safety of secukinumab up to 52 weeks. Methods This was a 52-week study with 12-week double-blind placebo-controlled treatment followed by 12-week open-label treatment and 6-month open-label extension treatment in all patients. Synovitis and ultrasound enthesitis response were measured by GLOESS and Global OMERACT enthesitis score (definitions 1 and 2) at patient level, respectively. Other assessments across key PsA manifestations of joints (ACR responses), enthesitis, (SPARCC), skin (PASI responses), dactylitis (LDI) and physical function (HAQ-DI) were also evaluated. Data are presented as observed. Results A total of 166 patients were enrolled, of which 90% (75/83) of secukinumab and 83% (69/83) of placebo-secukinumab participants completed 52 weeks. A continued improvement in GLOESS was observed in both secukinumab and placebo-secukinumab groups after switching to active therapy at Week 12 through Week 52 and a similar trend of improvement in Global OMERACT enthesitis score (definition 1 and 2) was observed up to 52 weeks in both groups (Table). At 52 weeks, sustained clinical response rates were observed in secukinumab (ACR20, 89%; ACR50, 68%; ACR70, 48%; PASI 90, 59%; PASI 100, 55%) and placebo-secukinumab groups (ACR20, 84%; ACR50, 72%; ACR70, 47%; PASI 90, 74%; PASI 100, 48%). Mean changes from baseline at Week 52 in HAQ-DI and SPARCC were -3.0 and -0.8 and -3.6 and -0.7 for secukinumab and placebo-secukinumab, respectively. There were no new or unexpected safety findings. Conclusion ULTIMATE demonstrated the responsiveness of ultrasound on both synovitis and enthesitis outcomes in PsA supporting its use in clinical trials, and confirmed the rapid and continued benefits of secukinumab through 52 weeks. Sustained efficacy was also observed across key clinical PsA manifestations with a safety profile consistent with previous reports. Disclosure P.G. Conaghan: Consultancies; AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer. Member of speakers’ bureau; AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer. M.A. D’Agostino: Consultancies; Sanofi, Novartis, BMS, Janssen, Celgene, Roche, AbbVie, UCB, Eli Lilly. Member of speakers’ bureau; Sanofi, Novartis, BMS, Janssen, Celgene, Roche, AbbVie, UCB, Eli Lilly. G. Schett: Member of speakers’ bureau; AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche, UCB. C. Guerrero: None. P. Hanova: None. T. Cazenave: None. M.S. Stoenoiu: Honoraria; Roche, AbbVie, BMS, Gilead, Jonsson, MSD, Novartis, Pfizer, UCB. Member of speakers’ bureau; Roche, AbbVie, UCB. Grants/research support; Roche, AbbVie, UCB. M. Backhaus: Honoraria; Roche, AbbVie, BMS, Gilead, Jonsson, MSD, Novartis, Pfizer, UCB. Member of speakers’ bureau; Roche, AbbVie, UCB. Grants/research support; Roche, AbbVie, UCB. G. Mouterde: Consultancies; AbbVie, Lilly. Honoraria; AbbVie, BMS, Lilly, Novartis, Pfizer, Roche, Chugai, UCB. Grants/research support; Celgene, Pfizer. M. Boers: Consultancies; BMS, Novartis, Pfizer, GSK. A. Duggan: Other; Employee of Novartis. P. Goyanka: Other; Employee of Novartis MSD. C. Gaillez: Shareholder/stock ownership; Novartis, BMS. Other; Employee of Novartis.

What Constitutes a Positive MRI for Clinical Trial Recruitment of Psoriatic Arthritis Patients With Axial Involvement?

There has been a resurgence of interest in defining the axial inflammation component of psoriatic arthritis (PsA) since recent randomized controlled trials (RCTs) raised the possibility that this entity may respond differentially to therapeutics compared to patients with axial spondyloarthritis. A workshop was conducted during the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis annual meeting to review the literature on diagnosing PsA and to determine which criteria might be most appropriate. There was quite strong agreement that magnetic resonance imaging (MRI) had an important role to play in helping to define axial inflammation in PsA and that a data-driven methodology for generating optimal MRI quantitative cut-offs for lesions in the sacroiliac joints and/or spine that reflect imaging typical of axial inflammation in PsA would be most desirable.

Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects

Psoriatic arthritis (PsA) is an underdiagnosed entity with a broad impact on the quality of life. Although the pathogenesis is largely unknown, autoimmune footprints of the inflammation in PsA have increasingly been recognized. Most of the genetic variation predisposing to PsA is mapped to the class I major histocompatibility complex (MHC) region and shared by a variety of autoimmune diseases. Polymorphisms in the genes IL12B, IL23R, IL13, TNIP1, TRAF3IP2, TYK2, and many others explain the non-HLA genetic risk with little known functional consequences. Entheseal and synovial cellular infiltrate with oligoclonal CD8+ T cells and occasional germinal centers, loss of regulatory T cell function, and specific autoantibodies such as anti-PsA peptide, anti-LL-37, and anti-ADAMTSL5 are the immunopathological findings suggestive of autoimmunity. These were supported by clinical observations of autoimmune multimorbidity and treatment response to calcineurin/mTOR and co-stimulation inhibition.

From Bed to Bench and Back: TNF-α, IL-23/IL-17A, and JAK-Dependent Inflammation in the Pathogenesis of Psoriatic Synovitis.

Psoriatic arthritis (PsA) is a chronic inflammatory immune-mediated disease with a burdensome impact on quality of life and substantial healthcare costs. To date, pharmacological interventions with different mechanisms of action, including conventional synthetic (cs), biological (b), and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs), have been proven efficacious, despite a relevant proportion of failures. The current approach in clinical practice and research is typically “predictive”: the expected response is based on stratification according to clinical, imaging, and laboratory data, with a “heuristic” approach based on “trial and error”. Several available therapeutic options target the TNF-α pathway, while others are directed against the IL-23/IL-17A axis. Janus kinase inhibitors (JAKis), instead, simultaneously block different pathways, endowing these drugs with a potentially “broad-spectrum” mechanism of action. It is not clear, however, whether targeting a specific pathway (e.g., TNF-α or the IL-23/IL-17 axis) could result in discordant effects over other approaches. In particular, in the case of “refractory to a treatment” patients, other pathways might be hyperactivated, with opposing, synergistic, or redundant biological significance. On the contrary, refractory states could be purely resistant to treatment as a whole. Since chronic synovitis is one of the primary targets of inflammation in PsA, synovial biomarkers could be useful in depicting specific biological characteristics of the inflammatory burden at the single-patient level, and despite not yet being implemented in clinical practice, these biomarkers might help in selecting the proper treatment. In this narrative review, we will provide an up-to-date overview of the knowledge in the field of psoriatic synovitis regarding studies investigating the relationships among different activated proinflammatory processes suitable for targeting by different available drugs. The final objective is to clarify the state of the art in the field of personalized medicine for psoriatic disease, aiming at moving beyond the current treatment schedules toward a patient-centered approach.

Drivers of Inflammation in Psoriatic Arthritis: the Old and the New.

The recognition that IL-17 is produced by many lymphoid-like cells other than CD4+ T helper (Th17) cells raises the potential for new pathogenic pathways in IBD/psoriasis/SpA. We review recent knowledge concerning the role of unconventional and conventional lymphocytes expressing IL-17 in human PsA and axSpA. Innate-like lymphoid cells, namely gamma delta (γδ) T-cells, invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells, together with innate lymphoid cells (ILCs) are found at sites of disease in PsA/SpA. These cells are often skewed to Type-17 profiles and may significantly contribute to IL-17 production. Non-IL-23 dependent IL-17 production pathways, utilising cytokines such as IL-7 and IL-9, also characterise these cells. Both conventional CD4 and CD8 lymphocytes show pathogenic phenotypes at sites of disease. A variety of innate-like lymphoid cells and conventional lymphocytes contribute towards IL-17-mediated pathology in PsA/SpA. The responses of these cells to non-conventional immune and non-immune stimuli may explain characteristic clinical features of these diseases and potential therapeutic mechanisms of therapies such as Jak inhibitors.

Proteinase-Mediated Macrophage Signaling in Psoriatic Arthritis.

ObjectiveMultiple proteinases are present in the synovial fluid (SF) of an arthritic joint. We aimed to identify inflammatory cell populations present in psoriatic arthritis (PsA) SF compared to osteoarthritis (OA) and rheumatoid arthritis (RA), identify their proteinase-activated receptor 2 (PAR2) signaling function and characterize potentially active SF serine proteinases that may be PAR2 activators.MethodsFlow cytometry was used to characterize SF cells from PsA, RA, OA patients; PsA SF cells were further characterized by single cell 3’-RNA-sequencing. Active serine proteinases were identified through cleavage of fluorogenic trypsin- and chymotrypsin-like substrates, activity-based probe analysis and proteomics. Fluo-4 AM was used to monitor intracellular calcium cell signaling. Cytokine expression was evaluated using a multiplex Luminex panel.ResultsPsA SF cells were dominated by monocytes/macrophages, which consisted of three populations representing classical, non-classical and intermediate cells. The classical monocytes/macrophages were reduced in PsA compared to OA/RA, whilst the intermediate population was increased. PAR2 was elevated in OA vs. PsA/RA SF monocytes/macrophages, particularly in the intermediate population. PAR2 expression and signaling in primary PsA monocytes/macrophages significantly impacted the production of monocyte chemoattractant protein-1 (MCP-1). Trypsin-like serine proteinase activity was elevated in PsA and RA SF compared to OA, while chymotrypsin-like activity was elevated in RA compared to PsA. Tryptase-6 was identified as an active serine proteinase in SF that could trigger calcium signaling partially via PAR2.ConclusionPAR2 and its activating proteinases, including tryptase-6, can be important mediators of inflammation in PsA. Components within this proteinase-receptor axis may represent novel therapeutic targets.

Ultrasound characteristics of osteophytes in psoriatic arthritis

Objective. To assess the relationship between ultrasound and clinical characteristics of psoriatic arthritis (PsA) and osteophytes detected by ultrasound (US).Methods. Data collection: demographical, clinical, antropometric (body mass index, BMI). US examination included 868 joints and 3348 entheses (bilateral shoulders, acromioclavicular joints, elbows, wrists, hips, knees, ankles; entheses at the projection of these joints (total number is 54). In the joints – synovitis count, Power Doppler (PD) + synovitis count (SC), the number of joints with osteophytes; in entheses – Grey Scale (GS) enthesitis count (EC), PD + EC, count of entheses with structural components (erosion, enthesophytes, calcification).Results. In all, 62 PsA patients were examined: 32 (51.6%) were women, mean age was 43.0 ± 10.4 years, the duration of PsA was 7 (3; 10) years. The number of joints with osteophytes was 314 of 868 (36.2%). US osteophytes were detected in 51 (82.3%) patients. The number of joints with osteophytes correlated with GS EC (r = 0.398; p &lt; 0.01), PD + EC (r = 0.302; p &lt; 0.05), SC (r = 0.425; p &lt; 0.01), and PD + SC (r = 0.322; p &lt; 0.05). Patients without osteophytes, with local and generalized osteophytes were comparable by sex and duration of the disease. In patients with generalized osteophytes, GS EC (p &lt; 0.05), PD + SC (p &lt; 0.05), SC (p &lt; 0.01), comorbid pathology (p &lt; 0.05), BMI (p &lt; 0.05) were significantly higher.Conclusion. The frequency of osteophytes in patients with PsA was high. The number of synovitis and enthesitis, both GC and PD+, was more common in patients with generalized osteophytes, which probably suggests an important role of entheseal and synovial inflammation in PsA in the development of osteophytes. BMI and the frequency of comorbidities in patients with generalized osteophytes were higher.

Power Doppler Ultrasound Assessment of A1 Pulley. A New Target of Inflammation in Psoriatic Arthritis?

Objective: To determine the prevalence of grey scale and power Doppler (PD) ultrasound (US) features of A1 pulley inflammation in a cohort of psoriatic arthritis (PsA) patients compared with rheumatoid arthritis (RA) patients.Methods: Sixty patients (30 with PsA and 30 with RA) were consecutively enrolled. The main clinimetric indexes were recorded, and US assessment of A1 pulleys from second to fifth fingers bilaterally was carried out. The presence of A1 pulley inflammation, defined as PD signal within a thickened pulley, was registered.Results: A1 pulley inflammation was found in 15 of 240 fingers (6.3%) of eight PsA patients (26.7%) and in one of 240 fingers (0.4%) of one RA patient (3.3%) (p < 0.01 and p = 0.03, respectively). Seven of eight PsA patients (88%) with at least one inflamed A1 pulley had a moderate/high disease activity score. The regression linear analysis (R2 = 0.36, adjusted R2 = 0.31) showed that A1 pulley inflammation was correlated with Disease Activity Index for Psoriatic Arthritis (DAPSA) (β = 0.43, p = 0.03).Conclusion: US A1 pulley inflammation appears to be relatively common at patient level in PsA, seems to be a characteristic feature of PsA compared to RA, and correlates with DAPSA.