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Objective To assess sex differences in disease activity parameters and health-related quality of life in PsA, and to assess whether determinants associated with not reaching treatment target differed between men and women. Methods Routine practice data of 855 PsA patients, who were all tightly monitored and treated, was used. Sex differences including, but not limited to, PsA Disease Activity Score (PASDAS), skin/nail disease, SF-12 PCS/MCS, and inflammatory back pain (IBP) were assessed. Multivariate analyses were used to examine determinants associated with not reaching treatment target (PASDAS ≤ 3.2) in men and women. Results Women had worse scores for—among others—swollen and tender joints, CRP, enthesitis and function (all P < 0.001). Higher PASDAS scores were found for women [3.5  (1.5)] than men [2.7  (1.5), P < 0.001]. Likewise, women were more often not at PASDAS treatment target (OR = 2.03, P < 0.001). No difference in current medication use was found. Nail disease, IBP, number of DMARDs used (past and current), and BMI were associated with not reaching treatment target in the overall sample. For women, but not men, BMI was associated with not reaching PASDAS low disease activity (LDA) (OR between 2.41 and 3.43, P < 0.001). Conclusions Women with PsA in a tightly monitored and treated setting have more severe disease than men. This is demonstrated by worse scores for women in both subjective and objective disease activity measures, in addition to women less often reaching the treatment target. Notably, being overweight is associated with higher disease activity in women, but not men. [ABSTRACT FROM AUTHOR]

The article presents information on a research conducted to assess the role of innate lymphoid cells (ILCs) in the pathogenesis of rheumatic diseases. Particular focus is given to topics including a comparison between ILCs and Helper T cells, models of ILC development, and composition of ILC in psoriasis.

Objective The prevalence of periodontitis is increased in patients with rheumatoid arthritis (RA), and the severity of periodontitis can affect the level of arthritis. Porphyromonas gingivalis is one of the main bacteria involved in periodontitis. Our aim was to determine if there are differences in the innate immune response against P gingivalis between healthy controls and RA patients. Methods Monocyte-derived dendritic cells (DCs) from healthy controls, RA patients, and patients with psoriatic arthritis (PsA) were stimulated with P gingivalis, a range of other bacteria, and Toll-like receptor agonists. Cytokine production was determined, and blocking studies were performed to determine which receptors were involved in differential recognition of P gingivalis. Effects on T cell cytokines were also determined in cultures of peripheral blood mononuclear cells (PBMCs). Results Upon stimulation with P gingivalis, RA patient DCs produced less tumor necrosis factor as compared to healthy control DCs, which was not observed in PsA patients or upon stimulation with other bacteria. In addition, P gingivalis-mediated activation of RA patient PBMCs showed a clear reduction of interferon-γ production. Among the various possible underlying mechanisms investigated, only blockade of CR3 abolished the difference between RA patients and healthy controls, suggesting the involvement of CR3 in this process. Conclusion Immune cells from RA patients display a reduced response to P gingivalis, which has functional consequences for the immune response. This may result in prolonged survival of P gingivalis, possibly driving autoantibody formation and a self-perpetuating loop of chronic inflammation. The possible role of CR3 in this process warrants further investigation. [ABSTRACT FROM AUTHOR]

Rheumatic diseases can be divided in two groups, autoinflammatory and autoimmune disorders. The clinical presentation of both types of diseases overlap, but the pathological pathways underlying rheumatic autoinflammation and autoimmunity are distinct and are the subject of ongoing research. There are a number of ways in which these groups of diseases differ in terms of disease mechanisms and therapeutic responses. First, autoinflammatory diseases are driven by endogenous danger signals, metabolic mediators and cytokines, whereas autoimmunity involves the activation of T and B cells, the latter requiring V-(D)-J recombination of receptor-chain gene segments for maturation. Second, the efficacy of biologic agents directed against proinflammatory cytokines (for example IL-1β and TNF) also highlights differences between autoinflammatory and autoimmune processes. Finally, whereas autoinflammatory diseases are mostly driven by inflammasome-induced IL-1β and IL-1β production, autoimmune diseases are associated with type I interferon (IFN) signatures in blood. In this Review, we provide an overview of the monocyte intracellular pathways that drive autoinflammation and autoimmunity. We convey recent findings on how the type I IFN pathway can modulate IL-1β signalling (and vice versa), and discuss why IL-β-mediated autoinflammatory diseases do not perpetuate into autoimmunity. The origins of intracellular autoantigens in autoimmune disorders are also discussed. Finally, we suggest how new mechanistic knowledge of autoinflammatory and autoimmune diseases might help improve treatment strategies to benefit patient care. [ABSTRACT FROM AUTHOR]

Background: Little is known about the extent of impairments in work and activities of daily life (ADL) in patients with psoriasis, and the influence of contextual factors such as disease-related characteristics and treatment. Therefore, this study aimed to assess these impairments in patients with psoriasis who started using biologicals/small molecule inhibitors. Methods: Using data from the prospective BioCAPTURE registry, we collected patient, disease, and treatment parameters, as well as work/ADL impairments at baseline, 6 and 12 months. Changes in impairment parameters and correlations between impairment and patient/disease characteristics were assessed using generalized estimating equations. Results: We included 194 patients in our analysis. After biological initiation, disease activity decreased significantly (PASI 11.2 at baseline versus 3.9 at 12 months, p<0.001). Work-for-pay in this cohort was lower than in the Dutch general population (53% versus 67%, p=0.01). In patients who had work-for-pay, presenteeism improved over time (5% at baseline versus 0% at 12months, p=0.04). Up to half of the patients reported impairments in ADL, which did not change over time. Associations between impairments and contextual factors varied, but all impairments were associated with worse mental/physical general functioning. Conclusion: Patients with psoriasis using biologicals are less likely to have work-for-pay. Treatment improves the work productivity of employed patients, but we were unable to detect changes in ADL performance. [ABSTRACT FROM AUTHOR]

Background: In rheumatoid arthritis (RA) macrophages play a major role in amplifying synovial inflammation. Important activating signals are those induced by Toll-like receptor (TLR) ligands and by activated T cells. The balance between activating and inhibitory Fc gamma receptors (FcγRs) on macrophages might be crucial in modulating these inflammatory responses. The purpose of this study was to determine FcγR expression on pro- and anti-inflammatory macrophages (gmMφ and mMφ, respectively) and identify functional consequences on immune complex uptake and macrophage activation. Methods: Human monocytes were isolated and differentiated into gmMφ and mMφ. A full FcγR characterization of both macrophage subtypes was performed and uptake of fluorescent immune complexes (ICs) was determined. FcγRIIb isoforms were determined by qPCR. Macrophages were stimulated via different TLRs or cytokine activated T cells in the presence or absence of ICs and cytokine production was determined. Blocking studies were performed to look into the pathways involved. Results: mMφ expressed high levels of the activating FcγRIIa and FcγRIII and low levels of the inhibitory FcγRIIb, while the FcγR balance on gmMφ was shifted towards the inhibitory FcγRIIb. This was accompanied by a clear increase in FcγRIIb1 mRNA expression in gmMφ. This resulted in higher IC uptake by mMφ compared to gmMφ. Furthermore, FcγR-mediated stimulation of gmMφ inhibited TLR2, 3, 4 and 7/8 mediated cytokine production via FcγRIIb and PI3K signaling. In addition, gmMφ but not mMφ produced TNFα upon co-culture with cytokine activated T cells, which was reduced by IC binding to FcγRIIb. The latter was dependent on PI3K signaling and COX2. Conclusions: FcγR expression patterns on gmMφ and mMφ are significantly different, which translates in clear functional differences further substantiating FcγRIIb as an interesting target for inflammation control in RA and other autoimmune/inflammatory diseases. [ABSTRACT FROM AUTHOR]

Patients with psoriasis are at risk of developing psoriatic arthritis, which can lead to joint damage. While screening questionnaires have been developed, their performance varies. The objective of this study was to develop a referral tool for dermatologists to identify psoriasis patients with concomitant psoriatic arthritis for rheumatological referral. This study used data from the DAPPER study, in which psoriasis patients were screened by a rheumatologist for the presence of concomitant psoriatic arthritis. Multivariable regression analysis was used to identify predictive variables for the presence of concomitant psoriatic arthritis: treatment history with conventional systemic drugs (odds ratio (OR) 2.97, 95% confidence interval (95% CI) 1.01–8.74, p=0.04), treatment history with biologicals/small molecule inhibitors (OR 2.90, 95% CI 1.52– 5.53, p=0.01), patient-reported history of joint pain not caused by trauma (OR 4.23, 95% CI 1.21–14.79, p=0.01), patient-reported history of swollen joints (OR 4.25, 95% CI 2.17–8.32, p<0.001), and patientreported history of sausage-like swollen digits (OR 2.38, 95% CI 1.25–4.55, p=0.01). Based on these variables, a referral tool was created with an area under the curve of 0.82. This referral tool could be used to aid dermatologists to identify psoriasis patients with concomitant psoriatic arthritis, who may benefit from rheumatological referral. [ABSTRACT FROM AUTHOR]

Objective The aim of the study was to determine the Minimal Important Change (MIC) values and Meaningful Change (MCV) values for the Psoriatic Arthritis Disease Activity Score (PASDAS) and the Standard Error of Measurement (s. e. m.) of the PASDAS. Methods The routine practice data for 544 patients with PsA was available for analysis. An anchor-based method using linear regression analyses was used to determine the MICs and MCVs for the PASDAS. With this anchor-based method, we compared changes in the PASDAS score with an external reference (anchor). The anchor question inquired whether the patient's well-being had changed since their previous visit. It consisted of a 7-point Likert scale (range: very much improved to very much deteriorated). Interperiod correlation matrix analysis was performed to determine the s. e. m. Results The overall MIC and MCV for the PASDAS were 0.67 (95% CI: 0.55, 0.79) and 1.34 (95% CI: 1.21, 1.46), respectively. Results for improvement and deterioration were 0.65 (95% CI: 0.46, 0.83) and 0.71 (95% CI: 0.49, 0.93) for the MIC, respectively, and 1.29 (95% CI: 1.11, 1.48) and 1.42 (95% CI: 1.19, 1.64) for the MCV, respectively. The s. e. m. was determined at 0.81. Conclusion The MIC for the PASDAS is a tool for physicians treating patients with PsA enabling them to give context to the patient's perspective of disease activity, while the MCV might aid the use of the PASDAS in PsA clinical trials. [ABSTRACT FROM AUTHOR]

Patients with psoriasis are at risk of developing psoriatic arthritis, which can lead to irreversible joint damage. However, a proportion of patients with psoriasis and concomitant psoriatic arthritis remain undiscovered in practice. The aims of this study were: to prospectively determine prevalence, characteristics, and disease burden of psoriatic arthritis in a psoriasis population; and to determine the prevalence and characteristics of patients with active psoriatic arthritis, who were not under rheumatological care. Patients with psoriasis were screened by a rheumatologist at the dermatology outpatient clinic for psoriatic arthritis. Patients with suspected active psoriatic arthritis who were not seeing a rheumatologist were referred to a rheumatologist for confirmation. The total prevalence of psoriatic arthritis in this observational, prospective cohort (n = 303) was 24%. Patients with psoriasis with concomitant psoriatic arthritis had longer duration of skin disease and more often a treatment history with systemic therapies. In this academic, specialized, setting, 2.3% of patients (n = 7), were not receiving rheumatological care despite having active psoriatic arthritis. These patients were characterized by a combination of low (perceived) disease burden and low yield of screening questionnaires, making it difficult for dermatologists to discover psoriatic arthritis in these patients. Thus, screening for more subtle active arthritis in patients with psoriasis in a dermatology setting could be improved. [ABSTRACT FROM AUTHOR]

An abstract of the conference paper "Macrophage dysfunction in Psoriatic Arthritis," by several researchers including, Mark H. Wenink, Kim C. M. Santegoets, and John Butcher is presented.

An abstract of the conference paper "Impaired dendritic cell proinflammatory cytokine production in psoriatic arthritis," by several researchers including, Mark H. Wenink, Kim C. M. Santegoets, and John Butcher is presented.

Objectives We aimed to investigate the disease activity and overall disease burden of (subgroups of) patients with PsA using the Psoriatic Arthritis Disease Activity Score (PASDAS) in an already tightly monitored cohort. Methods This is a cross-sectional study evaluating data from the first visit of 855 PsA patients after implementation of the PASDAS in our tightly monitored cohort [e.g. DAS 28 (DAS28) was provided as an anchor]. Differences in clinical outcomes between subgroups of patients using established cut-offs for disease activity status [i.e. very low (VLDA), low (LDA), moderate (MDA), and high disease activity (HDA)] were examined. Results Based on the PASDAS, 53.1% of patients were in VLDA/LDA. 29.5% of patients had ≥1 swollen joint, 20.6% had ≥1 enthesitis index point and 3.0% had active dactylitis. Based on DAS28, 77.5% of the patients were in VLDA/LDA. Patients reaching both DAS28 VLDA/LDA status and PASDAS VLDA/LDA status [ N  = 445 (52.0%)] were compared with patients reaching only DAS28 VLDA/LDA status [ N  = 218 (25.5%)]. For these latter patients, significantly worse scores on separate parameters were found in measures used for PASDAS/DAS28 calculation (e.g. swollen and tender joint count and patient's visual analogue scale global disease activity) as well as other disease measures (e.g. function and inflammatory back pain). This result remained, even when the stricter VLDA cut-off was used for the DAS28. Conclusion PASDAS implementation uncovered relevant residual disease activity in a quarter of patients previously assessed as being in DAS28 VLDA/LDA, underscoring the potential value of PASDAS measurements in PsA clinical care. [ABSTRACT FROM AUTHOR]

Background: Both methotrexate (MTX) and leflunomide (LEF) are registered and regularly prescribed as first-line treatments for the use in patients with psoriatic arthritis (PsA) and they are occasionally used in combination. However, evidence about their individual, and especially combined efficacy, in PsA is lacking. The aim of this study is to compare the effectiveness and safety of MTX and LEF combination therapy to MTX monotherapy in patients with PsA.Methods: COMPLETE-PsA is a randomized, placebo-controlled, double-blind clinical trial. Disease-modifying antirheumatic drug (DMARD)-untreated patients (n = 78) with clinical diagnosis of active (i.e. ≥2 swollen joints) PsA will be randomized 1:1 (stratified for high disease activity, Psoriatic Arthritis Disease Activity Score [PASDAS] ≥ 5.4) to the combination or monotherapy. The intervention group receives MTX 25 mg (oral or subcutaneous) once weekly plus LEF 20 mg daily, and the control group receives the same but with placebo instead of LEF daily. Primary endpoint is between-group difference in PASDAS at 16 weeks, adjusted for baseline PASDAS. Key secondary parameters include between-group comparisons in change in Disease Activity in Psoriatic Arthritis (DAPSA) score, skin score, enthesitis score, dactylitis score, and swollen/tender joint count, as well as the proportion of patients fulfilling minimal disease activity (MDA), American College of Rheumatology (ACR) 20/50/70 response criteria at week 16. Furthermore, safety, function and quality of life (Health Assessment Questionnaire [HAQ], Psoriatic Arthritic Impact of Disease [PSAID], Short Form 12 [SF-12]) will be assessed.Discussion: This is, to our knowledge, the first randomized, placebo-controlled, double-blind clinical trial assessing the effectiveness of MTX and LEF combination therapy in patients with PsA. The study will provide important information for treatment strategies and treatment recommendations.Trial Registration: Dutch Trial Register NTR7632 (3 December 2018). CMO NL66544.091.18 (19 November 2018). [ABSTRACT FROM AUTHOR]

Background: Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies.Methods: We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), ≥ 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total.Discussion: More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences.Trial Registration: Dutch Trial Register, NL6771. Registered on 27 November 2018 (CMO NL66181.091.18, 23 October 2018). [ABSTRACT FROM AUTHOR]

Background: Although patients have different treatment preferences, these individual preferences could often be grouped in subgroups with shared preferences. Knowledge of these subgroups as well as factors associated with subgroup membership supports health care professionals in the understanding of what matters to patients in clinical decision-making. Objectives: To identify subgroups of patients with rheumatoid arthritis (RA) based on their shared preferences toward disease-modifying antirheumatic drugs (DMARDs), and to identify factors associated with subgroup membership. Methods: A discrete choice experiment to determine DMARD preferences of adult patients with RA was designed based on a literature review, expert recommendations, and focus groups. In this multicenter study, patients were asked to state their preferred choice between two different hypothetical treatment options, described by seven DMARD characteristics with three levels within each characteristic. Latent class analyses and multinomial logistic regressions were used to identify subgroups and the characteristics (patient characteristics, disease-related variables, and beliefs about medicines) associated with subgroup membership. Results: Among 325 participating patients with RA, three subgroups were identified: an administration-driven subgroup (45.6%), a benefit-driven subgroup (29.7%), and a balanced subgroup (24.7%). Patients who were currently using biologic DMARDs were significantly more likely to belong to the balanced subgroup than the administration-driven subgroup (relative risk ratio (RRR): 0.50, 95% CI: 0.28–0.89). Highly educated patients were significantly more likely to belong to the benefit-driven subgroup than the balanced subgroup (RRR: 11.4, 95% CI: 0.97–133.6). Patients' medication-related concerns did not contribute significantly to subgroup membership, whereas a near-significant association was found between patients' beliefs about medication necessity and their membership of the benefit-driven subgroup (RRR: 1.12, 95% CI: 1.00–1.23). Conclusion: Three subgroups with shared preferences were identified. Only biologic DMARD use and educational level were associated with subgroup membership. Integrating patient's medication preferences in pharmacotherapy decisions may improve the quality of decisions and possibly medication adherence. [ABSTRACT FROM AUTHOR]

Objective. Innate lymphoid cells (ILCs) are a recently discovered group of cells that are essential to epithelial homeostasis and are implicated in psoriasis pathogenesis, yet they have never been reported in psoriatic arthritis (PsA). Methods. ILC classes and subsets were characterized in the peripheral blood (PB) of healthy controls, patients with psoriasis, and patients with PsA and in the synovial fluid (SF) of patients with PsA and patients with rheumatoid arthritis (RA). Cell surface marker expression and intracellular cytokine production following stimulation were analyzed using flow cytometry. Results. ILCs were identified in the SF and were 4-fold more abundant in PsA SF than in PsA PB. Fewer CCR61 ILCs were found in PsA PB than in healthy control PB, while PsA SF was enriched for CCR61 ILCs compared to PsA PB and RA SF. Natural cytotoxicity receptor NKp441 group 3 ILCs were rare in PB and RA SF, but abundant in PsA SF. Increased numbers of interleukin-17A (IL-17A)–producing ILCs were present in PsA SF compared to RA SF. CCR6, NKp44, and melanoma cell adhesion molecule (MCAM) were expressed on the cell surface of SF ILCs that produced IL-17A. The number of circulating NKp441, CCR61, and MCAM1 ILCs in blood was inversely correlated with PsA disease activity. Conclusion. Our findings indicate that PsA SF is enriched for group 3 ILCs that express CCR6 and NKp44, which distinguishes the synovial compartment from RA. The increased IL-17A production by SF ILCs indicates a novel role for ILCs in PsA. [ABSTRACT FROM AUTHOR]

A correction to the article "Measuring Disease Activity in Psoriatic Arthritis: PASDAS Implementation in a Tightly Monitored Cohort Reveals Residual Disease Burden," that was published in a previous issue is presented.

Background: Costimulation of murine macrophages with immune complexes (ICs) and TLR ligands leads to alternative activation. Studies on human myeloid cells, however, indicate that ICs induce an increased pro-inflammatory cytokine production. This study aimed to clarify the effect of ICs on the pro- versus anti-inflammatory profile of human polarized macrophages. Materials and Methods: Monocytes isolated from peripheral blood of healthy donors were polarized for four days with IFNγ, IL-4, IL-10, GM-CSF, M-CSF, or LPS, in the presence or absence of heat aggregated gamma-globulins (HAGGs). Phenotypic polarization markers were measured by flow cytometry. Polarized macrophages were stimulated with HAGGs or immobilized IgG alone or in combination with TLR ligands. TNF, IL-6, IL-10, IL-12, and IL-23 were measured by Luminex and/ or RT-qPCR. Results: HAGGs did not modulate the phenotypic polarization and the cytokine production of macrophages. However, HAGGs significantly altered the TLR-induced cytokine production of all polarized macrophage subsets, with the exception of MWIL-4. In particular, HAGGs consistently enhanced the TLR-induced IL-10 production in both classically and alternatively polarized macrophages (M1 and M2). The effect of HAGGs on TNF and IL-6 production was less pronounced and depended on the polarization status, while IL-23p19 and IL-12p35 expression was not affected. In contrast with HAGGs, immobilized IgG induced a strong upregulation of not only IL-10, but also TNF and IL-6. Conclusion:HAGGs alone do not alter the phenotype and cytokine production of in vitro polarized human macrophages. In combination with TLR-ligands, however, HAGGs but not immobilized IgG shift the cytokine production of distinct macrophage subsets toward IL-10. [ABSTRACT FROM AUTHOR]

Psoriasis (Pso) is a chronic inflammatory skin disease, and up to 30% of Pso patients develop psoriatic arthritis (PsA), which can lead to irreversible joint damage. Early detection of PsA in Pso patients is crucial for timely treatment but difficult for dermatologists to implement. We, therefore, aimed to find disease-specific immune profiles, discriminating Pso from PsA patients, possibly facilitating the correct identification of Pso patients in need of referral to a rheumatology clinic. The phenotypes of peripheral blood immune cells of consecutive Pso and PsA patients were analyzed, and disease-specific immune profiles were identified via a machine learning approach. This approach resulted in a random forest classification model capable of distinguishing PsA from Pso (mean AUC = 0.95). Key PsA-classifying cell subsets selected included increased proportions of differentiated CD4+CD196+CD183-CD194+ and CD4+CD196-CD183-CD194+ T-cells and reduced proportions of CD196+ and CD197+ monocytes, memory CD4+ and CD8+ T-cell subsets and CD4+ regulatory T-cells. Within PsA, joint scores showed an association with memory CD8+CD45RA-CD197- effector T-cells and CD197+ monocytes. To conclude, through the integration of in-depth flow cytometry and machine learning, we identified an immune cell profile discriminating PsA from Pso. This immune profile may aid in timely diagnosing PsA in Pso. [ABSTRACT FROM AUTHOR]

The article discusses a study which showed better clinical outcomes of treat-to-target (T2T) in psoriatic arthritis (PsA) compared with usual care using minimal disease activity (MDA) criteria as treatment targets. Topics covered include a routine measurement of Psoriatic Arthritis Disease Activity Score (PASDAS) that was implemented in the study, the different stages of the implementation process, and clinical outcome of the study.