Untreated Psoriatic Arthritis Research Articles

Candidate Biomarkers For Response To Treatment In Psoriatic Disease.

To determine whether biologic therapy alters serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in psoriatic arthritis (PsA) and psoriasis (PsC) patients, and whether baseline levels of these proteins predict response to treatment for PsA. We included PsA patients on TNF inhibitors (TNFi), Interleukin-17 inhibitors (IL-17i), methotrexate (MTX), and untreated with bDMARDs or csDMARDs (untreated) and PsC patients on bDMARDs and matched untreated. Serum samples at baseline and 3-6 months follow-up were retrieved from the biobank. Protein levels were quantified using a Luminex multiplex assay. We compared follow-up vs baseline protein levels within groups and change in levels between groups. For the predictive potential of the biomarkers, we developed logistic regression classification models. Response to treatment was defined as: 1. Achieving low disease activity or remission (according to DAPSA), 2. 75% reduction in PASI, and 3. 50% reduction in actively inflamed joint count. In PsA, TNFi reduced serum levels of all five proteins, IL-17i increased ACP5 and CCL2, and MTX reduced MMP3. Changes in MMP3 and S100A8 levels were significantly different between untreated PsA and matched biologic-treated PsA (p<0.05). There were no significant differences between treated or untreated PsC patients. Baseline levels of CXCL10, MMP3, S100A8, and ACP5 had good predictive value (AUC>0.8) for response to biologics in PsA patients. Biologics treatment and MTX affect serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in PsA patients. MMP3, S100A8, ACP5, and CXCL10 have potential use as serum biomarkers to predict response to treatment for PsA.

E072 The psoriatic arthritis disease activity score demonstrates excellent test-retest reliability in early, untreated psoriatic arthritis

Abstract Background/Aims Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterised by heterogenous clinical features including peripheral arthritis, spondylitis, enthesitis, dactylitis, skin and nail disease. Historically, outcome measures in PsA trials focused on the articular manifestations of disease, with a recent emphasis in composite tools. The Psoriatic Arthritis Disease Activity Score (PASDAS) is a validated, composite measure with defined cut-off and excellent responsiveness when compared with other PsA-specific and non-specific composite measures. Although PASDAS is one of the recommended GRAPPA measures for research trials, data on its test-retest reliability are limited particularly in PsA of short disease duration. Aims and Objectives - To assess the test-retest reliability of the PASDAS composite index in a cohort of early, untreated PsA patients. Methods Data were collected from a subset of participants recruited to the GOLMePsA clinical trial (EudraCT Number: 2013-004122-28), after a minor protocol amendment enabling additional data collection at the screening visit. The test-retest reliability of PASDAS was performed by calculating the intraclass correlation coefficient (ICC) between measurements collected at screening and baseline time-points (maximum 4 weeks apart, by protocol). Table 1 details the sample size calculation. Baseline variables collected in the GOLMePsA trial were described by absolute numbers, percentages, means, medians, absolute and inter-quartile ranges (IQR). Results The PASDAS test-retest reliability was assessed in 37 consecutive participants. Average time between the two time-points was 1.9 weeks (range 0.4 to 4.0). Baseline characteristics of test-retest subset compared to all GOLMePsA participants were similar (table 1). The ICC was 0.85 (95% confidence interval 0.73-0.92). The observed ICC was identical to the value assumed in the sample size calculation for this analysis, yielding an acceptably narrow confidence interval around the estimate. There was no substantial correlation between the means of the two measurements and the differences between them (Pearson’s r=-0.26). The Bland-Altman limits of agreement were -0.11 ± 1.24 (-1.35 to 1.13). Conclusion These results confirm the excellent test-retest reliability of PASDAS in early, untreated PsA, supporting its use as an outcome measure in interventional studies in newly diagnosed disease of short-duration. Disclosure G. De Marco: Consultancies; Janssen, Novartis. E.M.A. Hensor: None. D.G. McGonagle: Consultancies; AbbVie, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB. Grants/research support; AbbVie, BMS, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB. A. Tan: None. L.C. Coates: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB. Honoraria; AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB. Grants/research support; AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB. P. Emery: None. P.S. Helliwell: None. H. Marzo Ortega: Consultancies; AbbVie, Celgene, Eli-Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB. Grants/research support; Janssen, Novartis and UCB.

High prevalence of radiographic erosions in early, untreated PsA: results from the SpARRO cohort

AimsTo investigate the prevalence and distribution of bone erosions in an early psoriatic arthritis (PsA) population using conventional radiography (CR) and to explore the agreement between CR and ultrasound (US)...

Circulating Immune Landscape Profiling in Psoriasis Vulgaris and Psoriatic Arthritis by Mass Cytometry.

Psoriasis, a systemic disorder mediated by the immune system, can appear on the skin, joints, or both. Individuals with cutaneous psoriasis (PsC) have an elevated risk of developing psoriatic arthritis (PsA) during their lifetime. Despite this known association, the cellular and molecular mechanisms underlying this progression remain unclear. We performed high-dimensional, in-depth immunophenotyping of peripheral blood mononuclear cells (PBMCs) in patients with PsA and psoriasis vulgaris (PsV) by mass cytometry. Blood samples were collected before and after therapy for a longitudinal study. Then three sets of comparisons were made here: active PsA vs. active PsV, untreated PsV vs. treated PsV, and untreated PsA vs. treated PsA. Marked differences were observed in multiple lymphocyte subsets of PsA related to PsV, with expansion of CD4+ T cells, CD16- NK cells, and B cells. Notably, two critical markers, CD28 and CD127, specifically differentiated PsA from PsV. The expression levels of CD28 and CD127 on both Naïve T cells (TN) and central memory CD4+ T cells (TCM) were considerably higher in PsA than PsV. Meanwhile, after treatment, patients with PsV had higher levels of CD28hi CD127hi CD4+ TCM cells, CD28hi CD127hi CD4+ TN cells, and CD16- NK cells. In the circulation of PsA patients, the TN and CD4+ TCM are characterized with more abundant CD28 and CD127, which effectively distinguished PsA from PsV. This may indicate that individuals undergoing PsV could be stratified at high risk of developing PsA based on the circulating levels of CD28 and CD127 on specific cell subsets.

Rheumatoid Factor as a Potentiator of Anti-Citrullinated Protein Antibody-Mediated Inflammation in Early Undifferentiated Seronegative Osteoarthropathy

Abstract Introduction. To compare the values and accuracy of the test in anticyclic citrullinated peptides antibodies, rheumatoid factor (RF), C-reactive protein (CRP) and disease activity index in early diagnosis of untreated psoriatic arthritis (PsA). Methods. Using the ELISA method of DIA-STATTM Anti CCP (Axis-Shield Diagnostics), sera of 70 participants were examined (35 untreated patients with PsA and 35 subjects from the healthy control group). RF and CRP were determined with the agglutination test (latex test). At the same time the sensitivity, specificity, predictive value for positive and negative testsand accuracy were determined. Results. Of 35 patientswith PsA, 1 patient showed presence of anti-CCP antibodies (sensitivity test 2.86%), while RF was foundin 0 patients(sensitivity test 0%). In the healthy control group positivevalues for RF, CRP and erythrocyte sedimentation rate were detected in 1 patient. Conclusion. ACPA antibodies have low sensitivity, but high specificity in PsA.

Some Aspect of Accuracy of Acpa Assay in Patients with Psoriatic Arthritis

Aims:To compare the values and acuracy of the test in anticyclic citrullinatedpeptides (Anti-CCP /ACPA) antibodies, Rheumatoid factor (RF), C-Reactive Protein (CRP) and disease activity index (PASI) in early diagnosis of untreated Psoriatic arthritis(PsA).Methods:Using the ELISA method of DIA-STATTM Anti CCP (Axis–Shield Diagnostics), sera of 70 participants were examined (35 untreated patients with PsA and 35 persons from the healthy control group). RF and CRP were determined with the agglutination test (Lateks test) in the same participants. In the same time we determined the sensitivity, specificity, predictive value for positive and negative test and accuracy.Results:From 35 pts with PsA, 1 patient showed presence of Anti-CCP antibodies (sensitivity test 2.86%), while RF was present in 0 pts (sensitivity test 0%). In the healthy control group positive values for RF, CRP and Erythroid Sedimentation Rate (ESR) were detected in 1 participant.Conclussion:ACPA antibodies have low sensitivity, but high specificity in PsA.Key words: Anti cyclic citrullinated peptide (Anti-CCP) Psoriatic arthritis (PsA), Rheumatoid factor (RF)

Interleukin (IL)-9/IL-9R axis drives γδ T cells activation in psoriatic arthritis patients.

Cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-12, interferon (IFN)-γ, IL-23 and, more recently, IL-9, have been implicated in the initiation/maintenance of inflammation in psoriasis and psoriatic arthritis (PsA). In the present study we aimed to characterize the role of γδ T cells in peripheral blood and synovial fluid of PsA patients and to investigate their response to in-vitro stimulation with antigen or cytokines (IL-9 and IL-23). γδ T cells isolated from peripheral blood mononuclear cells and synovial fluid were analysed by flow cytometry to evaluate the phenotype and cytokine production. IL-23R and IL-9R gene expression were also evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Peripheral blood mononuclear cells (PBMC), sorted γδ T cells and γδ cell lines were also stimulated in vitro with isopentenyl pyrophosphate (IPP), recombinant IL-9 or recombinant IL-23. Our results show an expansion of γδ T cells with a predominant effector memory phenotype in peripheral blood and synovium of untreated PsA patients, which reverses significantly after treatment with anti-TNF-α or anti-IL-12/IL-23R monoclonal antibodies (mAbs). Moreover, in PsA patients γδ T cells activation is driven prevalently by IL-9/IL-9R interaction, and not only by IL-23/IL-23R. Together these findings indicate γδ T cells and IL-9 as new players in the pathogenesis of PsA.

Management of psoriatic arthritis from the view of the dermatologist

Psoriatic arthritis (PsA) is an inflammatory seronegative spondyloarthropathy associated with psoriasis. Although the main assessment measures for PsA are borrowed from the standard criteria used to assess rheumatoid arthritis, a number of new criteria such as the PsAJAI and CPDAI are being developed specifically for PsA. Long-term consequences of untreated PsA include persistent inflammation, progressive joint damage and, in many cases, substantial functional limitations, pain and disability. Moreover, patients with PsA have an increased mortality risk and an increased risk of developing cardiovascular disease and metabolic syndrome. Both GRAPPA and the AAD have developed treatment guidelines, which are discussed here. Psoriasis commonly precedes arthritic symptoms; thus, dermatologists are ideally placed to make the initial diagnosis of PsA and treat it appropriately, affording the opportunity to slow disease progression, improve physical function and enhance quality of life. This Review explores the management of patients with PsA, with a particular emphasis on assessment tools, long-term consequences and treatment issues from the viewpoint of the dermatologist.