Peripheral Psoriatic Arthritis Research Articles

E011 Magnetic resonance imaging in axial spondyloarthritis: usage, reporting times and scanning times - a service evaluation in a large tertiary centre

Abstract Background/Aims Rapid access to magnetic resonance imaging (MRI) of the spine and sacroiliac joints is essential for the timely diagnosis of axial spondyloarthritis (axSpA). A recent NASS/BRITSpA national FOI survey highlighted deteriorating waiting times to access MRI for the assessment of inflammatory back pain in the UK, with only 73% of Trusts reporting access within 8 weeks, compared to 90% in 2017. In addition, NHS England and the Royal College of Radiologists have recently published a target of 28 days for turn-around time (TAT) for a verified report to be provided after image acquisition in any circumstance. Aims: To evaluate the usage of MRI performed under the “inflammatory back pain protocol” at a large tertiary centre, including the time from MRI request to scan being performed, TAT for reporting and whether this has changed over time. Methods A service evaluation audit was conducted at Leeds Teaching Hospitals Trust (LTHT). MRIs of the spine and sacroiliac joints requested between December 2021 and May 2023 under the local “inflammatory back pain protocol” were identified by the radiology department. Data extracted from medical records included: indication for MRI request, time elapsed from request to scan, and from scan to verified report. Results A total of 668 MRI requests were identified. The commonest reason for MRI request was to aid the diagnosis of axSpA 75% (n = 501); followed by disease activity monitoring in established axSpA (16.7%, n = 111) and assessment of axial involvement in peripheral psoriatic arthritis, i.e. diagnosis of axPsA (8.5% n = 57 scans). The majority (92%) had a request to scan time of 8 weeks, with a TAT to report of 4 weeks (77%). However, a greater delay in TAT to verified report was seen from December 2022 to May 2023 with <45% of reports issued within 28 days, despite no change in scanning time. Causes identified were related to local workforce issues including delays in appointing new radiographers and radiology consultants. Conclusion The main reason for request of an MRI under the inflammatory back pain protocol at LTHT is to support making a diagnosis of axSpA. A significant number of patients were scanned for treatment monitoring and to diagnose axial psoriatic arthritis, although data on the utility of MRI for these indications are limited. Whilst nearly all patients were scanned within 2 months at all time periods, the TAT to report has significantly deteriorated since December 2022 in our region, due to workforce issues. Further understanding of the impact of workforce factors on service delivery in rheumatology is required. Disclosure J. Weddell: None. R. Shah: None. P. Robinson: None. A. Barr: None. C. Vandevelde: None. J. Freeston: None. D. McGonagle: None. H. Marzo-Ortega: None.

Clinical Characteristics of "Severe" Peripheral Psoriatic Arthritis: A Retrospective Analysis of a Longitudinal Cohort.

The concept of severity in a multidomain disease such as psoriatic arthritis (PsA) is still not well defined. The aim of this study was to identify the clinical characteristics of patients with severe peripheral PsA. Retrospective analysis of a longitudinal cohort. Demographic and clinical characteristics of patients with PsA were collected at baseline and at last follow-up. We defined the severe population using the modified Composite Psoriatic Disease Activity Index (mCPDAI); which excludes ankylosing spondylitis quality of life scale). Hence, patients with a score of 3 in at least one domain were defined as having severe PsA. Clinical characteristics of patients fulfilling the definition of severe PsA were compared to those non-severe. We evaluated 177 patients with peripheral PsA (M/F: 98/76). Of these, 64 (36.1%) were identified as severe according to the mCPDAI criteria, at baseline. Eighteen patients (10.1%) at last follow-up still met the definition of severe PsA. At last follow-up visit, severe patients with PsA were only males (18/18, P < 0.01) and have worse outcomes in terms of disease activity, pain, function, and impact of disease. Male sex and the severity of skin involvement at baseline were factors associated with the presence of severe PsA. The agreement between the presence of severe PsA and the absence of minimal disease activity was slight [Cohen's k: 0.174 (0.084-0.264)]. Our study showed that severe patients with PsA had more disease activity, pain, and impact of disease than non-severe patients. Furthermore, we demonstrated that severity and disease activity are not interchangeable concepts.

Serum proteome analysis identifies a potential biomarker for axial psoriatic arthritis

BackgroundTo identify potential serum biomarkers for differentiating between axial psoriatic arthritis (axPsA) and peripheral psoriatic arthritis (pPsA).MethodsSerum samples were collected from patients with PsA to create a biomarker discovery cohort and a verification cohort. Patients with PsA were classified into axial or peripheral subtypes based on imaging criteria. Untargeted proteomics technology was used in the discovery phase to screen for biomarkers, and candidate biomarkers were evaluated using enzyme-linked immunosorbent assay (ELISA) in the verification phase.ResultsWe identified 45 significantly differentially expressed proteins (DEPs) between axPsA (n = 20) and pPsA (n = 20) with liquid chromatography-mass spectrometry. Among these DEPs, serum pigment epithelium-derived factor (PEDF) was identified as a candidate biomarker using the Boruta algorithm and lasso regression. Results of ELISA further confirmed that the level of serum PEDF expression was significantly higher in axPsA (n = 37) than in pPsA (n = 51) at the verification cohort (37.9 ± 10.1 vs. 30.5 ± 8.9 μg/mL, p < 0.001). Receiver operating characteristics analysis showed that PEDF had an area under the curve (AUC) of 0.72. Serum PEDF was positively correlated with body mass index and C-reactive protein. Additionally, there was a tendency towards a positive correlation between PEDF and the Bath Ankylosing Spondylitis Disease Activity Index.ConclusionsThis study provided a comprehensive characterization of the proteome in axPsA and pPsA and identified a candidate biomarker, PEDF, that may contribute to early diagnosis for axPsA.

Critical importance of patient-reported outcomes for a comprehensive assessment of psoriatic arthritis patients.

Psoriatic arthritis (PsA) is a heterogeneous, chronic inflammatory disease that negatively impacts patients' quality of life. Patient-reported outcome measures (PROMs) are used to capture patient perspectives in disease assessment, and physicians use the Disease Activity Index for Psoriatic Arthritis (DAPSA) to evaluate disease activity in PsA. The study aimed to assess the relationship between PROMs and the DAPSA score in consecutive outpatients affected by PsA. A cross-sectional study was conducted from March 2018 to October 2020 at the PsA clinic of the ARNAS Civico in Palermo (Italy), enrolling outpatients with PsA. Patients were assessed for their disease activity according to the DAPSA score, and PROMs, such as PHQ-9, HAQ, FACIT-F, and PsAID, were evaluated. Linear regression analysis evaluated the relationship between the DAPSA Score and the included PROMs. 158 PsA consecutive peripheral subset psoriatic arthritis outpatients were recruited. The median years of illness was 10.6 (9.3-11.9), and the median DAPSA score was 19.02 (9-33.1). The regression analysis highlighted a strong relationship between the DAPSA score and the PsAID (adjR2 26%, p < 0.0001), the FACIT-F (adjR2 25.4%, p < 0.0001), the HAQ (adjR2 23.7%, p < 0.0001), and PHQ-9 (adjR2 15%, p < 0.0001). PROMs are strongly associated with the DAPSA score, but it allows in-depth evaluation of the impact of the disease on different domains of PsA patients' life.

Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: exploratory findings from the FLORA trial

ObjectivesThe gut microbiota can mediate both pro and anti-inflammatory responses. In patients with psoriatic arthritis (PsA), we investigated the impact of faecal microbiota transplantation (FMT), relative to sham transplantation, on...

Use of the Bath Ankylosing Spondylitis Disease Activity Index in Patients With Psoriatic Arthritis With and Without Axial Disease.

To evaluate whether the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a responsive instrument in psoriatic arthritis (PsA) and whether it differentiates between axial and peripheral disease activity in PsA. Individuals with PsA initiating therapy in a longitudinal cohort study based in the United States were included. Axial PsA (axPsA), most often also associated with peripheral disease, was defined as fulfillment of the Assessment of Spondyloarthritis international Society axial spondyloarthritis classification criteria or presence of axial disease imaging features. Baseline BASDAI, individual BASDAI items, patient global assessment, patient pain, and Routine Assessment of Patient Index Data 3, and score changes following therapy initiation were descriptively reported. Standardized response means (SRMs) were calculated as the mean change divided by the SD of the change. The mean (SD) baseline BASDAI score at the time of therapy initiation was 5.0 (2.2) among those with axPsA (n = 40) and 4.8 (2.0) among those with peripheral-only disease (n = 79). There was no significant difference in patient-reported outcome scores between the groups. The mean change for BASDAI was similar among axial vs peripheral disease (-0.75 vs -0.83). SRMs were similar across axial vs peripheral disease for BASDAI (-0.37 vs -0.44) and the individual BASDAI items. BASDAI has reasonable responsiveness in PsA but does not differentiate between axPsA and peripheral PsA. (ClinicalTrials.gov: NCT03378336).

Symposium 8

Psoriatic arthritis (PsA) is a chronic inflammatory autoimmune condition characterized by inflamed joints. PsA often, but not always, occurs along with psoriasis (PsO), an autoimmune skin condition that results in scaly, red itchy patches. Biologics therapy has been a standard of treatment for moderate to severe PsA after the use of disease-modifying antirheumatic drugs (DMARDs). Traditionally PsA biologics targeted on inhibiting the tumor necrosis factor (TNF) or interleukin-17 (IL-17) pathway to suppress the inflammatory triggering cascade. Recently biologics inhibiting the interleukin-23 (IL-23) pathway, such as guselkumab, is approved for the management of both PsA and PsO with promising efficacy in both skin and joint improvement. IL-23 inhibitors are included as recommended treatment option for peripheral and skin-involved PsA in the latest EULAR recommendations. With the availability of new mode of therapy, it is important to understand the characteristics and clinical evidence of different biologics modality and this lecture will demonstrate how to apply the various options to PsA patients presented with different disease profiles.

Ixekizumab Efficacy in Patients with Severe Peripheral Psoriatic Arthritis: A Post Hoc Analysis of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (SPIRIT-P1).

The efficacy and safety of ixekizumab, an anti-interleukin-17A antibody, in patients with severe symptoms of psoriatic arthritis are largely unexplored. We report the efficacy and safety of ixekizumab in a post hoc analysis of the SPIRIT-P1 trial. Patients were treated with placebo, ixekizumab 80mg every 2weeks (Q2W) or 4weeks (Q4W), or adalimumab 40mg Q2W for 24weeks. In this subgroup analysis of SPIRIT-P1, the population with severe psoriatic arthritis was defined using the modified composite psoriatic activity index total score > 7 and peripheral arthritis score = 3 (> 4 tender or swollen joint count and ≥ 0.5 Health Assessment Questionnaire-Disability Index). Efficacy was measured by joint and skin endpoints including disease progression. In the severe population, significantly more patients (p ≤ 0.001) treated with ixekizumab than placebo achieved 20% improvement according to the American College of Rheumatology criteria (ACR 20): 63.3% for ixekizumab Q4W, 60.4% for ixekizumab Q2W, and 24.5% for placebo. Statistically greater responses compared with placebo were observed in the severe population for ACR 50, ACR 70, ACR core set, disease activity index for psoriatic arthritis (DAPSA) low disease activity and DAPSA remission, and 28-joint disease activity score using C-reactive protein, as well as Psoriasis Area and Severity Index (PASI) 75, PASI 90, and PASI 100 (p ≤ 0.001). Efficacy findings and the safety profile of ixekizumab in the severe population were consistent with those of the overall population, with no new safety concerns identified. In patients with severe psoriatic arthritis, 24weeks of treatment with ixekizumab resulted in improvements in both joint and skin symptoms. The safety profile in the severe population was consistent with the established safety profile of ixekizumab. ClinicalTrials.gov identifier, NCT01695239.

Adoption rates of recommended vaccines and influencing factors among patients with inflammatory arthritis: a patient survey.

To determine the scope of recommended vaccination uptake among patients with inflammatory arthritis (IA) receiving biologic and targeted synthetic disease-modifying antirheumatic agents (bDMARDs and tsDMARDs, respectively) and to determine factors, which influence their decision and are subject to modification. A single-center, cross-sectional study was conducted including patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) on bDMARDs or tsDMARDs. Demographic, anthropometric, and clinical parameters were analyzed. Disease activity was determined using the validated indices DAS28-CRP and CDAI for RA and peripheral PsA, whereas BASDAI and ASDAS for AS and axial PsA. Patients completed a questionnaire with predefined response options assessing their vaccination status and attitudes about receiving a COVID-19 vaccination. A total of 201 patients with inflammatory joint diseases were included in the study, with a mean age of 54.6 (± 8.6) years and a disease duration of 11 (± 14.4) years. More than one-third of the study group had received full vaccination against SARS-CoV-2, with the majority (68.1%) receiving the BNT162b2 vaccine. The proportion of patients who had received recommended pneumococcal and influenza vaccinations and regular reimmunizations against diphtheria and tetanus was low, with only 13.9% (n = 28), 1.5% (n = 3), and 44.8% (n = 90), respectively. Patients who had a preceding discussions with a rheumatologist were more likely to get vaccinated. Considering the suboptimal vaccination rates and the prevalent uncertainty among individuals with IA in Bulgaria, there is an urgent need to devise novel strategies to promote vaccination uptake and enhance patient awareness. These strategies aim to educate patients about their autoimmune condition, as well as emphasize the safety and efficacy of vaccines.

Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial.

We investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate-treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT). This exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate-treatment, were included in a 26-week, double-blind, 1:1 randomized, sham-controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n=15) or sham (n=16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose-to-mannitol ratio (LMR) test at baseline (n=31) and at week 26 (n=26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using 1 H Nuclear Magnetic Resonance. Trial failures (n=7) had significantly higher LMR compared with responders (n=19) at week 26 (0.027 [0.017-0.33]) vs. 0.012 [0-0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n=19) versus failures (n=12) at all time points based on their fecal (P < 0.0001) and plasma (P = 0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P = 1). Fecal N-acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient=0.50; P = 0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient=27, P = 0.02). Intestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.

Treatment-related changes in serum neutrophil gelatinase-associated lipocalin (NGAL) in psoriatic arthritis: results from the PIPA cohort study

Objectives Obesity and psoriatic arthritis (PsA) have a complicated relationship. While weight alone does not cause PsA, it is suspected to cause worse symptoms. Neutrophil gelatinase-associated lipocalin (NGAL) is secreted through various cell types. Our objective was to assess the changes and trajectories in serum NGAL and clinical outcomes in patients with PsA during 12 months of anti-inflammatory treatment. Method This exploratory prospective cohort study enrolled PsA patients initiating conventional synthetic or biological disease-modifying anti-rheumatic drugs (csDMARDs/bDMARDs). Clinical, biomarker, and patient-reported outcome measures were retrieved at baseline, and 4 and 12 months. Control groups at baseline were psoriasis (PsO) patients and apparently healthy controls. The serum NGAL concentration was quantified by a high-performance singleplex immunoassay. Results In total, 117 PsA patients started a csDMARD or bDMARD, and were compared indirectly at baseline with a cross-sectional sample of 20 PsO patients and 20 healthy controls. The trajectory in NGAL related to anti-inflammatory treatment for all included PsA patients showed an overall change of −11% from baseline to 12 months. Trajectories in NGAL for patients with PsA, divided into treatment groups, showed no clear trend in clinically significant decrease or increase following anti-inflammatory treatment. NGAL concentrations in the PsA group at baseline corresponded to the levels in the control groups. No correlation was found between changes in NGAL and changes in PsA outcomes. Conclusion Based on these results, serum NGAL does not add any value as a biomarker in patients with peripheral PsA, either for disease activity or for monitoring.

Increased synovial immunohistochemistry reactivity of TGF-β1 in erosive peripheral psoriatic arthritis

BackgroundImmune and non-immune cells contribute to the pathology of chronic arthritis, and they can contribute to tissue remodeling and repair as well as disease pathogenesis. The present research aimed to analyze inflammation and bone destruction/regeneration biomarkers in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and ankylosing spondylitis (AS).MethodsSamples were obtained from the inflamed knee of patients with knee arthritis who had been referred for undergoing arthroscopies. The synovial membrane was processed for pathological description, IHC analysis, and quantification of mRNA expression ratio by qRT-PCR. Serum levels of TGF-β1, IL-23, IL-6, IL-17 A, IL-22, Dkk1, Sclerostin, BMP2, BMP4, Wnt1, and Wnt5a were measured by ELISA. All these data were analyzed and compared with the demographic, clinical, blood tests, and radiological characteristics of the patients.ResultsThe synovial membrane samples were obtained from 42 patients for IHC, extraction, and purification of RNA for synovial mRNA expression analysis, and serum for measuring protein levels from 38 patients. IHC reactivity for TGF-β1 in the synovial tissue was higher in patients with psoriatic arthritis (p 0.036) and was positively correlated with IL-17 A (r = 0.389, p = 0.012), and Dkk1 (r = 0.388, p = 0.012). Gene expression of the IL-17 A was higher in PsA patients (p = 0.018) and was positively correlated with Dkk1 (r = 0.424, p = 0.022) and negatively correlated with BMP2 (r = -0.396, p = 0.033) and BMP4 (r = -0.472, p = 0.010). It was observed that IHC reactivity for TGF-β1 was higher in patients with erosive PsA (p = 0.024).ConclusionsThe IHC reactivity of TGF-β1 in synovial tissue was higher in patients with erosive psoriatic arthritis, and TGF-β1 was in relation to higher levels of gene expression of IL-17 A and Dkk1.

Arthritis Hit Rate in Patients with Psoriasis Referred for Rheumatology Evaluation

Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis that occurs in a large proportion of patients with psoriasis causing pain and impaired quality of life. Early recognition and treatment are important as PsA may result in structural joint damage with a risk of reduced physical function. Objectives: The aim of this study was to determine the proportion of psoriasis patients with suspicion of PsA who are diagnosed with PsA or other rheumatologic conditions following referral from a dermatology department. Furthermore, the study aimed to identify clinical and patient-reported variables identifying patients with psoriasis in whom joint discomfort is an expression of PsA. Methods: This single-center retrospective study included all patients with psoriasis who had been referred for rheumatological evaluation on suspicion of PsA in the period from 2014 to 2018. Results: A total of 364 patient records were reviewed. This identified 106 patients with psoriasis who had been referred for rheumatologic evaluation on suspicion of PsA. Patients with a previous diagnosis of PsA were excluded from the analysis. Among the referred patients, 23.6% were diagnosed with either peripheral or axial PsA or both. A total of 23.6% were diagnosed with osteoarthritis and an additional 14.2% were diagnosed with inactive PsA. For patient-reported swollen joints and dermatologist-assessed swollen joints at referral, the positive predictive values/negative predictive values for a PsA diagnosis were 40%/100% and 50%/92%, respectively. Conclusion: In this study, 23.6% of patients with psoriasis symptoms suggestive of PsA were diagnosed with axial and/or peripheral arthritis following rheumatologic evaluation. Patient-reported swollen joints and dermatologist-assessed swollen joints indicated a high likelihood of peripheral PsA. Additionally, the absence of patient-reported swollen joints indicated a very low probability of establishing a diagnosis of peripheral PsA.

Apremilast for biologic-naïve, peripheral psoriatic arthritis, including patients with early disease: results from the APROACH observational prospective study

To evaluate the effect of the phosphodiesterase 4 inhibitor apremilast in biologic-naïve patients with early peripheral PsA in terms of disease activity, clinical manifestations, patient-perceived outcomes, as well as apremilast’s safety profile in routine care settings of Greece. Non-interventional, multicenter, 52-week prospective cohort study, enrolling biologic-naïve patients with early active peripheral PsA who started apremilast after intolerance or inadequate response (within the first 12 months of treatment) to an initial conventional synthetic (cs)DMARD treatment. Non-responder imputation was applied for missing data.In total, 167 consecutive patients (mean age: 52.5 years; median PsA duration: 0.9 years) were analyzed. At baseline, the median (interquartile range) clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score was 22.0 (16.0–29.0), with 86.8% of patients having at least moderate (29.3% high) disease activity; 87.4% had skin psoriasis, 37.7% nail psoriasis, 30.7% enthesitis, and 12.4% dactylitis. At 16, 24, and 52 weeks, 28.7, 42.5, and 48.5% of patients, achieved ≥ 50% improvement in their baseline cDAPSA score, respectively. At week 52, 55.6, 50, and 26.8% of evaluable patients achieved complete resolution of enthesitis, dactylitis and nail psoriasis, respectively. Improvements were also observed in patient’s health state assessed by the Psoriatic Arthritis Impact of Disease 12-item questionnaire, and health-related quality of life. The 52-week drug survival rate was 75%, while 13.8% of patients experienced at least one adverse drug reaction.Biologic-naïve patients with early PsA, treated with apremilast experienced significant improvements in disease activity, extra-articular manifestations and patient-centered outcomes, accompanied by a favorable tolerability profile.

Tofacitinib combined with local low-dose ixekizumab injection benefits those with peripheral psoriatic arthritis.

Tofacitinib combined with local low-dose ixekizumab injection benefits those with peripheral psoriatic arthritis.

Current characteristics of a population of psoriatic arthritis and gender disparities

Psoriatic arthritis (PsA) is a polymorphic disease associated with numerous comorbidities. The objective of this study was to describe the main clinicobiological and imaging characteristics of a population of PsA and to extract any disparities between men and women. A total of 132 patients in the rheumatology department of Amiens University Hospital with a confirmed diagnosis of PsA according to the CASPAR criteria were included over a period of 4 months. All data were collected retrospectively in this observational and single-center study. The sex ratio was 1 and the average age at inclusion was 54.9 years. Peripheral PsA was the predominant clinical form. Axial PsA represented 12.1% of cases. Enthesitis was noted in 52.3% of cases while dactylitis was identified in 29.5% of cases. Moreover, 12.1% had a joint symptomatology preceding the appearance of cutaneous signs. HLA-B*27 positivity was found in 33.3% of cases. Chronic hyperuricemia accounted for 10% of our population. Sacroiliitis was observed in 41% of cases. The disparities between men and women are multiple and consistent with the literature: Polyarticular form, enthesitis, obesity, more intensive prescription of s-DMARDs, and b-DMARDs are more associated with the female population. Oligoarticular form, psoriatic nail dystrophy, radiological axial involvement, and chronic hyperuricemia are more encountered in the male population. Our study found a very heterogeneous disease, with marked differences between men and women. Peripheral PsA remains predominant but the search for associated axial involvement, which is probably underestimated, seems essential. This work studied the main characteristics of patients with PsA followed in real life, in a regional university reference center. We have highlighted a very heterogeneous disease as well as some gender disparities, not well described in the literature, which should be taken into account in order to optimize therapeutic management.

Ex vivo cytokine production in psoriatic disease: Towards specific signatures in cutaneous psoriasis and peripheral psoriatic arthritis.

Psoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are different phenotypes of psoriatic disease (PsD), whose underlying specific mechanisms remain incompletely understood. As cytokines are key elements to induce and tune up immune responses to drive inflammatory diseases, our objective was to assess whether clinical features, disease phenotype and PsA and PsO activity were associated with a particular ex vivo cytokine production profile. Forty-eight patients (37 PsA and 11 PsO) and 11 healthy subjects (HS) were studied. Cytokine production by peripheral blood mononuclear cells (PBMC) that were either unstimulated, or stimulated with LPS or anti-CD3/CD28 antibodies, were analysed by multiplex assay in the culture supernatants. Cytokine signature of PsD includes a high level of TNFα in supernatants of LPS-stimulated PBMC, higher levels of IL-6 and lower levels of IFN-γ and IL-17A after CD3-CD28 stimulation, as well as higher spontaneous IL-1RA and TNFα production compared to HS. High body mass index (BMI) was associated with lower levels of IL-1β, and metabolic syndrome with lower levels of IFN-γ after LPS stimulation. In PsD, dermatological activity was related with higher IL-17A level, while rheumatic activity was linked with lower levels of IFN-γ and TNFα. Comparing each PsD subtype to HS, IL-1β and IL-6 productions are higher when using LPS stimulation in PsO patients with higher levels of IL-1β and IL-1α in peripheral PsA patients after CD3/CD28 stimulation. LPS stimulation induced high levels of IL-17A in peripheral PsA compared to axial PsA. PsA patients with axial PsA share some features with PsO but shows a distinct cytokine pattern compared to peripheral PsA. PsO and the different PsA subtypes exhibit distinct ex vivo cytokine production profiles and common features of the so-called PsD. Analysis of IL-1 cytokine family and IL-6 seems to be of particular interest to distinguish PsO and peripheral PsA since it depends on monocytes in PsO and T-lymphocytes in peripheral PsA. Peripheral cytokine profiles are influenced by rheumatic and dermatological activity of the disease, and also by metabolic syndrome features. Our results highlight the crucial role of immune cell interactions with different patterns of interaction depending on clinical phenotype.

Peripheral arthritis in psoriatic arthritis: from immunopathogenesis to therapy with Janus kinase inhibitors.

Psoriatic arthritis (PsA) is a chronic systemic inflammatory disease characterised by high phenotypic heterogeneity. Peripheral polyarticular, pauciarticular, axial, enthesitic, and dactylitic forms have been classically described, although it is not clear whether they all have the same pathophysiological mechanisms. Use of cytokine-targeted therapies in the last 20 years has significantly impacted the quality of life of patients with PsA even though a significant proportion of patients, regardless of the mechanism of action considered, remain non-responders, suggesting the need for better understanding of the pathophysiological basis of the disease to appropriately stratify patients and identify new therapeutic targets. The pre-clinical demonstration of the pathophysiological relevance of the JAK/STAT pathway in the pathogenesis of PsA and the emerging efficacy data from randomised controlled trials of JAK inhibitors in PsA patients have set the stage for a new pharmacological era in patients with PsA. In this review, we discuss the rationale for using approved JAK inhibitors for treatment of peripheral PsA and their positioning in the context of EULAR/GRAPPA guidelines.

Expert recommendations for the use of apremilast in psoriatic arthritis

Introduction and objectivesDespite the evidence, there are doubts about the positioning of apremilast in the psoriatic arthritis (PsA) treatment algorithm. The objective of this project was to collect the scientific evidence and the experience of a group of rheumatologists who are experts in the management of PsA with apremilast in clinical practice in Spain. Material and methodsA scientific committee made up of 6 experts proposed 5 clinical scenarios where the evidence on the use of apremilast in PsA was controversial: (i) Efficacy in peripheral PsA; (ii) Efficacy in enthesitis and dactylitis; (iii) Efficacy in PsA with skin involvement; (iv) Comorbidities; and (v) Apremilast safety. After this, a panel of 17 rheumatologists with expertise in PsA management discussed these scenarios and generated a questionnaire with 50 questions and 156 items following the Delphi methodology. This questionnaire was anonymously answered by the panel. ResultsAfter 2 voting rounds, the panel of experts reached consensus in 93 of the 156 items raised (59.6%) (67 in agreement and 26 in disagreement). The degree of consensus was 53.3% in the area of “Efficacy in peripheral PsA”; 60.0% in “Efficacy in enthesitis and dactylitis”; 50.0% in “Efficacy in PsA with skin involvement”; 57.1% in “Management of comorbidities in patients with PsA”; and 67.3% in “Implications of safety in the use of apremilast”. ConclusionsThe structured opinion of the experts complements the available evidence and contributes to the establishment of consensual guidelines for the use of apremilast in PsA.

Inconsistencies of the Disease Activity Assessment Tools for Psoriatic Arthritis: Challenges to Rheumatologists.

Currently, concerning the evaluation of psoriatic arthritis (PsA), there is no agreement on a standardized composite index for disease activity that includes all relevant domains. The present study sought to assess the rates of remission (REM)/low disease activity (LDA) and disease states [minimal disease activity (MDA), very low disease activity (VLDA)] as defined by diverse activity scales (DAPSA, DAS28-ESR) in an attempt to display discrepancies across these assessment tools for peripheral PsA. The study involved 758 patients (496 females, 262 males; mean age 47,1 years) with peripheral PsA who were registered to the Turkish League Against Rheumatism (TLAR) Network. The patients were assessed using the DAS28-ESR, DAPSA, MDA, and VLDA. The overall yield of each scale was assessed in identifying REM and LDA. The presence or absence of swollen joints was separately analysed. The median disease duration was 4 years (range 0-44 years). According to DAPSA and DAS28-ESR, REM was achieved in 6.9% and 19.5% of the patients, respectively. The rates of MDA and VLDA were 16% and 2.9%, respectively. Despite the absence of swollen joints, a significant portion of patients were not considered to be in REM (296 (39.1%) patients with DAS28-ESR, 364 (48%) with DAPSA, and 394 (52%) with VLDA). Patients with peripheral PsA may be assigned to diverse disease activity levels when assessed with the DAS28-ESR, DAPSA, MDA and VLDA, which would inevitably have clinical implications. In patients with PsA a holistic approach seems to be necessary which includes other domains apart from joint involvement, such as skin involvement, enthesitis, spinal involvement, and patient-reported outcomes.