Dual targeted therapy in patients with psoriatic arthritis and spondyloarthritis: a real-world multicenter experience from Spain

Dual targeted therapy (DTT) has emerged as a promising approach in patients with refractory spondyloarthritis (SpA) or psoriatic arthritis (PsA) and extra-musculoskeletal manifestations of both diseases, but its effectiveness/safety ratio still remains unclear. This is a retrospective, real-world multicenter study in refractory SpA and PsA patients with simultaneous use of two biological or synthetic targeted agents. Effectiveness was assessed using Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Disease Activity in Psoriatic Arthritis (DAPSA) Score. We identified 39 different DTT combinations in 36 patients (22 SpA; 14 PsA), 25 of them with concomitant inflammatory bowel disease. The most commonly used combinations were TNF inhibitor plus antagonist of the IL12/23 pathway, followed by TNF inhibitor plus IL-17 antagonist. During a median exposure of 14.86 months (IQR 8-20.2), DTT retention rate was 69.4% (n=25/36; 19 SpA, 6 PsA). Major clinical improvement (change in ASDAS-CRP > 2 or improvement > 85% in DAPSA) was achieved in 69.4% of patients (n=25/36 therapeutical combinations; 17/21 SpA, 8/15 PsA), with a 58.3% (n=21/36 combinations; 15/20 SpA, 6/13 PsA) low-activity/remission rate. Of the patients who were receiving glucocorticoids, 55% managed to withdraw them during follow-up. Interestingly, only four serious adverse events in three patients were observed, leading to DTT discontinuation

Lipoprotein(A) Concentrations In Rheumatoid Arthritis On Biologic Therapy: Results From The Cardiovascular In Rheumatology [Carma] Study Project

Background Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. Objective The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. Methods Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. Results Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (?: ?0.303, 95% confidence interval: ?0.558 to ?0.047; P = .02). Conclusions RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT.This project has been supported by an unrestricted grant from Abbvie, Spain. The design, analysis, interpretation of results, and preparation of the article have been done independently of Abbvie. Dr González-Gay's studies have been supported by grants from “Fondo de Investigaciones Sanitarias” PI06/0024, PS09/00748, and PI12/00060 and RD12/0009/0013 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain)

An international multicentre analysis of current prescribing practices and shared decision-making in psoriatic arthritis

Objectives Shared decision-making (SDM) is advocated to improve patient outcomes in PsA. We analysed current prescribing practices and the extent of SDM in PsA across Europe. Methods The ASSIST study was a cross-sectional observational study of PsA patients ≥18 years of age attending face-to-face appointments between July 2021 and March 2022. Patient demographics, current treatment and treatment decisions were recorded. SDM was measured by the clinician’s effort to collaborate (CollaboRATE questionnaire) and patient communication confidence (PEPPI-5 tool). Results A total of 503 patients were included from 24 centres across the UK, France, Germany, Italy and Spain. Physician- and patient-reported measures of disease activity were highest in the UK. Conventional synthetic DMARDs constituted a higher percentage of current PsA treatment in the UK than continental Europe (66.4% vs 44.9%), which differed from biologic DMARDs (36.4% vs 64.4%). Implementing treatment escalation was most common in the UK. CollaboRATE and PEPPI-5 scores were high across centres. Of 31 patients with low CollaboRATE scores (<4.5), no patients with low PsAID-12 scores (<5) had treatment escalation. However, of 465 patients with CollaboRATE scores ≥4.5, 59 patients with low PsAID-12 scores received treatment escalation. Conclusions Higher rates of treatment escalation seen in the UK may be explained by higher disease activity and a younger cohort. High levels of collaboration in face-to-face PsA consultations suggests effective implementation of the SDM approach. Our data indicate that in patients with mild disease activity, only those with higher perceived collaboration underwent treatment escalation. Prospective studies should examine the impact of SDM on PsA patient outcomes

Urine metabolome profiling of immune-mediated inflammatory diseases

Background: Immune-mediated inflammatory diseases (IMIDs) are a group of complex and prevalent diseases where disease diagnostic and activity monitoring is highly challenging. The determination of the metabolite profiles of biological samples is becoming a powerful approach to identify new biomarkers of clinical utility. In order to identify new metabolite biomarkers of diagnosis and disease activity, we have performed the first large-scale profiling of the urine metabolome of the six most prevalent IMIDs: rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn?s disease, and ulcerative colitis. Methods: Using nuclear magnetic resonance, we analyzed the urine metabolome in a discovery cohort of 1210 patients and 100 controls. Within each IMID, two patient subgroups were recruited representing extreme disease activity (very high vs. very low). Metabolite association analysis with disease diagnosis and disease activity was performed using multivariate linear regression in order to control for the effects of clinical, epidemiological, or technical variability. After multiple test correction, the most significant metabolite biomarkers were validated in an independent cohort of 1200 patients and 200 controls. Results: In the discovery cohort, we identified 28 significant associations between urine metabolite levels and disease diagnosis and three significant metabolite associations with disease activity (PFDR < 0.05). Using the validation cohort, we validated 26 of the diagnostic associations and all three metabolite associations with disease activity (PFDR < 0.05). Combining all diagnostic biomarkers using multivariate classifiers we obtained a good disease prediction accuracy in all IMIDs and particularly high in inflammatory bowel diseases. Several of the associated metabolites were found to be commonly altered in multiple IMIDs, some of which can be considered as hub biomarkers. The analysis of the metabolic reactions connecting the IMID-associated metabolites showed an overrepresentation of citric acid cycle, phenylalanine, and glycine-serine metabolism pathways. Conclusions: This study shows that urine is a source of biomarkers of clinical utility in IMIDs. We have found that IMIDs show similar metabolic changes, particularly between clinically similar diseases and we have found, for the first time, the presence of hub metabolites. These findings represent an important step in the development of more efficient and less invasive diagnostic and disease monitoring methods in IMIDs

The Impact of Comorbidity on Patient-Reported Outcomes in Psoriatic Arthritis: A Systematic Literature Review

INTRODUCTION: A systematic literature review was conducted with the aim to analyse the impact of comorbidity on patient-reported outcomes (PROs) in patients with psoriatic arthritis (PsA). METHODS: A sensitive search strategy of the Medline, Embase and the Cochrane Library (up to March 2019) was applied to retrieve studies for inclusion in this systematic literature review. Abstracts of the ACR and EULAR scientific meetings were also searched. The selection criteria were: (1) patients with PsA (population) with a comorbidity (intervention) and (2) report of any impact of the comorbidity on PROs. Systematic literature reviews, randomized controlled trials and observational were included in this systematic literature review. Two of the authors selected the articles and collected the data. RESULTS: Eighteen articles were included in this systematic literature review, with most being cross-sectional studies that included more than 9000 patients with PsA. Some studies analysed the impact of an individual comorbidity, such as fibromyalgia (FM), and in others the analysis was according to the number of comorbidities. The most frequently analysed PROs were function, quality of life and fatigue. Analysis of the studies included in the review showed that patients with a higher number of comorbidities and/or more severe comorbidities reported worse impacts of their disease on function, patient's global assessment (PGA), pain, fatigue, work disability and quality of life. Specifically, FM had a negative impact on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), function, quality of sleep and quality of life; anxiety and depression had a negative impact on function and fatigue; metabolic syndrome had a negative impact on BASDAI, function, PGA and quality of life; obesity had a negative impact on function and pain; smoking (current and ex-smokers) had a negative impact on pain, function, fatigue, quality of life and overall health; alcohol intake had a negative impact on pain, function, fatigue, quality of life and overall health. CONCLUSIONS: The prevalence and impact of medical comorbidity on PROs are very high in patients with PsA