Tumor Necrosis Factor Inhibitor Monotherapy Versus Combination Therapy for the Treatment of Psoriatic Arthritis: Combined Analysis of European Biologics Databases.

OBJECTIVE: To investigate whether tumor necrosis factor inhibitor (TNFi) combination therapy with conventional synthetic disease-modifying antirheumatic drugs (csDMARD) is more effective for psoriatic arthritis (PsA) and/or improves TNFi drug survival compared to TNFi monotherapy. METHODS: Five PsA biologics cohorts were investigated between 2000 and 2015: the ATTRA registry (Czech Republic); the Swiss Clinical Quality Management PsA registry; the Hellenic Registry of Biologics Therapies (Greece); the University of Bari PsA biologics database (Italy); and the Bath PsA cohort (UK). Drug persistence was analyzed using Kaplan-Meier and equality of survival using log-rank tests. Comparative effectiveness was investigated using logistic regression with propensity scores. Separate analyses were performed on (1) the combined Italian/Swiss cohorts for change in rate of Disease Activity Score in 28 joints (DAS28); and (2) the combined Italian, Swiss, and Bath cohorts for change in rate of Health Assessment Questionnaire (HAQ). RESULTS: In total, 2294 patients were eligible for the drug survival analysis. In the Swiss (P = 0.002), Greek (P = 0.021), and Bath (P = 0.014) databases, patients starting TNFi in combination with methotrexate had longer drug survival compared to monotherapy, while in Italy the monotherapy group persisted longer (P = 0.030). In eligible patients from the combined Italian/Swiss dataset (n = 1056), there was no significant difference between treatment arms in rate of change of DAS28. Similarly, when also including the Bath cohort (n = 1205), there was no significant difference in rate of change of HAQ. CONCLUSION: Combination therapy of a TNFi with a csDMARD does not appear to affect improvement of disease activity or HAQ versus TNFi monotherapy, but it may improve TNFi drug survival.

Cross-sectional study of patients with axial spondyloarthritis fulfilling imaging arm of ASAS classification criteria: baseline clinical characteristics and subset differences in a single-centre cohort.

OBJECTIVE: This study compared demographic, clinical and laboratory characteristics between patients with radiographic and non-radiographic axial spondyloarthritis (axSpA). METHODS: In this single-centre cross-sectional study, a total of 246 patients with axSpA fulfilling the imaging arm of Assessment of SpondyloArthritis International Society classification criteria were recruited. A total of 140 patients were diagnosed as non-radiographic axial spondyloarthritis (nr-axSpA), and 106 patients had ankylosing spondylitis (AS). Sociodemographic characteristics, disease manifestations, clinical and laboratory disease activity and their differences between subsets were analysed. P values below 0.05 with CI 95% were considered statistically significant. RESULTS: More nr-axSpA patients were women (61.4%) compared with 24.7% of AS patients. First symptoms developed earlier in AS patients compared with nr-axSpA (23.0 (IQR 17.5-30.0) vs 27.8 (IQR 21.0-33.7) years, p=0.001). Disease manifestations did not differ, but patients with nr-axSpA experienced peripheral arthritis more frequently (35.7% vs 17.0%, p=0.001) with less hip involvement (8.6% vs 18.9%, p=0.022) compared with patients with AS. Patients with AS exhibited worse spinal mobility and physical function compared with nr-axSpA. AS Disease Activity Scores and CRP levels were significantly higher in patients with AS compared with nr-axSpA (2.4 (IQR 1.7-2.8) vs 2.0 (IQR 1.1-2.3), p=0.022 and 7.1 (IQR 2.6-14.9) vs 2.5 (IQR 0.8-8.2) mg/L, p<0.001, respectively). CONCLUSIONS: Our data demonstrated some known and also novel differences between the two imaging arm fulfilling axSpA subgroups. Non-radiographic patients were mostly women who had experienced shorter disease duration, milder disease activity and better functional status with less hip involvement but more peripheral arthritis compared with patients with AS.

Circulating S100 proteins effectively discriminate SLE patients from healthy controls: a cross-sectional study.

S100 proteins are currently being investigated as potential diagnostic and prognostic biomarkers of several cancers and inflammatory diseases. The aims of this study were to analyse the plasma levels of S100A4, S100A8/9 and S100A12 in patients with incomplete systemic lupus erythematosus (iSLE), in patients with established SLE and in healthy controls (HCs) and to investigate the potential utility of the S100 proteins as diagnostic or activity-specific biomarkers in SLE. Plasma levels were measured by ELISA in a cross-sectional cohort study of 44 patients with SLE, 8 patients with iSLE and 43 HCs. Disease activity was assessed using the SLEDAI-2K. The mean levels of all S100 proteins were significantly higher in SLE patients compared to HCs. In iSLE patients, the levels of S100A4 and S100A12 but not S100A8/9 were also significantly higher compared to HCs. There were no significant differences in S100 levels between the iSLE and SLE patients. Plasma S100 proteins levels effectively discriminated between SLE patients and HCs. The area under the curve (AUC) for S100A4, S100A8/9 and S100A12 plasma levels was 0.989 (95% CI 0.976-1.000), 0.678 (95% CI 0.563-0.792) and 0.807 (95% CI 0.715-0.899), respectively. S100 levels did not differentiate between patients with high and low disease activity. Only the S100A12 levels were significantly associated with SLEDAI-2K and with cSLEDAI-2K. S100 proteins were significantly higher in SLE patients compared HCs and particularly S100A4 could be proposed as a potential diagnostic biomarker for SLE.

The relationship between synovitis quantified by an ultrasound 7-joint inflammation score and physical disability in rheumatoid arthritis - a cohort study.

BACKGROUND: Restoring normal physical functioning is a major therapeutic aim in the management of rheumatoid arthritis (RA). It is unknown, whether the extent of synovial inflammation quantified by musculoskeletal ultrasound (US) can predict current or future capacity for physical functioning. To answer this question we investigated the longitudinal relationship between physical function assessed by the health assessment questionnaire (HAQ) and the German 7-joint ultrasound score (US7S) in a prospective cohort of patients with RA. METHODS: Patients with RA (n = 185 (46 with incident and 139 with prevalent disease) were followed for 30.9 ± 9.1 months. Baseline and annual assessments comprised the disease activity score in 28 joints (DAS28), HAQ and US7S. The US7S includes semiquantitative measurements of synovitis assessed by greyscale (GS) and power Doppler (PD) in seven joints of the clinically dominant hand and foot, which are then aggregated in PD and GS synovitis sum-scores (PDsynSS and GSsynSS). A linear mixed-effect model was used to assess the longitudinal relationship between GSsynSS, PDsynSS and HAQ. We used standard and time-lag models to explore the association between HAQ, and GSsynSS, PDsynSS and DAS28 measured at the same time or at the previous visit 12 months ago, respectively. RESULTS: When the standard model was applied, in univariate analyses HAQ score was positively associated with GSsynSS and PDsynSS with ß coefficients significantly higher in incident than in prevalent disease. In multivariate analysis both synSSs were individually no longer significant predictors of HAQ score. When using the time-lag model, after adjustment for the previous DAS28 or HAQ score, both PDsynSS and GSsynSS were significantly and negatively associated with the current HAQ. CONCLUSIONS: US7 PD and GS synovitis sum-scores alone were positively associated with current functional status reflected by the HAQ in patients with RA, and this relationship was stronger in patients with early disease. When combined with the DAS28 or HAQ, US7 PD and GS synovitis sum-scores were predictive of the change in HAQ score over one year.