Background: Mortality is increased in rheumatoid arthritis (RA), mainly because of cardiovascular (CV) events, cancer and infections. Recent data suggest that treatment with tumour necrosis factor (TNF) antagonists may affect this trend. Objective: To assess whether treatment with TNF antagonists is associated with reduction in CV events, cancer and infection rates, and in mortality in patients with RA treated and not treated with TNF antagonists. Methods: BIOBADASER is a registry for active long-term follow-up of safety of biological treatments in patients with RA. It includes 4459 patients with RA treated with TNF antagonists. EMECAR is an external RA cohort (n = 789) established to define the characteristics of the disease in Spain and to assess comorbidity. The incidence density (ischaemic heart disease) of CV events, cancer and infections was estimated and compared. The standardised mortality ratio was compared with the rate in the general population. A propensity score was used to match cohorts by the probability of being treated. Results: Rates of CV and cancer events are significantly higher in EMECAR than in BIOBADASER (RR 5-7 for different CV events, and RR 2.9 for cancer), whereas the rate of serious infections is significantly higher in BIOBADASER (RR 1.6). Mortality ratio of BIOBADASER by EMECAR is 0.32 (0.20-0.53) for all causes of death, 0.58 (0.24-1.41) for CV events, 0.52 (0.21-1.29) for infection and 0.36 (0.10-1.30) for cancerrelated deaths. Conclusion: Morbidity, other than infection, and mortality are not higher than expected in patients with RA treated with TNF antagonists.

To investigate the incidence of COVID-19 in a cohort of adult and paediatric patients with rheumatic diseases receiving targeted biologic and synthetic disease modifying anti-rheumatic drugs (tDMARDs) and to explore the possible effect of these treatments in the clinical expression of COVID-19. Methods: A cross-sectional study comprising of a telephone survey and electronic health records review was performed including all adult and paediatric patients with rheumatic diseases treated with tDMARDs in a large rheumatology tertiary centre in Barcelona, Spain. Demographics, disease activity, COVID-19 related symptoms and contact history data were obtained from the start of the 2020 pandemic. Cumulative incidence of confirmed cases (SARS-CoV-2 positive PCR test) was compared to the population estimates for the same city districts from a governmental COVID-19 health database. Suspected cases were defined following WHO criteria and compared to those without compatible symptoms. Results: 959 patients with rheumatic diseases treated with tDMARDs were included. We identified 11 confirmed SARS-CoV-2 positive cases in the adult cohort and no confirmed positive cases in the paediatric cohort. COVID-19 incidence rates of the rheumatic patient cohort were very similar to that of the general population [(0.48% (95% CI 0.09 to 0.87%)] and [0.58% (95% CI 0.56 to 0.60%)], respectively. We found significant differences in tDMARDs proportions between the suspected and non-suspected cases (p=0.002). Conclusion: Adult and paediatric patients with rheumatic diseases on tDMARDs do not seem to present a higher risk of COVID-19 or a more severe disease outcome when compared to general population.

BackgroundTNF alpha blockade agents like infliximab are actually the treatment of choice for those rheumatoid arthritis (RA) patients who fail standard therapy. However, a considerable percentage of anti-TNF alpha treated patients do not show a significant clinical response. Given that new therapies for treatment of RA have been recently approved, there is a pressing need to find a system that reliably predicts treatment response. We hypothesized that the analysis of whole blood gene expression profiles of RA patients could be used to build a robust predictor to infliximab therapy.Methods and FindingsWe performed microarray gene expression analysis on whole blood RNA samples from RA patients starting infliximab therapy (n = 44). The clinical response to infliximab was determined at week 14 using the EULAR criteria. Blood cell populations were determined using flow cytometry at baseline, week 2 and week 14 of treatment. Using complete cross-validation and repeated random sampling we identified a robust 8-gene predictor model (96.6% Leave One Out prediction accuracy, P = 0.0001). Applying this model to an independent validation set of RA patients, we estimated an 85.7% prediction accuracy (75–100%, 95% CI). In parallel, we also observed a significantly higher number of CD4+CD25+ cells (i.e. regulatory T cells) in the responder group compared to the non responder group at baseline (P = 0.0009).ConclusionsThe present 8-gene model obtained from whole blood expression efficiently predicts response to infliximab in RA patients. The application of the present system in the clinical setting could assist the clinician in the selection of the optimal treatment strategy in RA.

Objective. To identify new genes associated with susceptibility to rheumatoid arthritis (RA), using a 2-stage genome-wide association study.Methods. Following a liability-based study design, we analyzed 317,503 single-nucleotide polymorphisms (SNPs) in 400 patients with RA and 400 control subjects. We selected a group of candidate SNPs for replication in an independent group of 410 patients with RA and 394 control subjects. Using data from the 3 previous genome-wide association studies in RA, we also looked for genomic regions showing evidence of common association signals. Finally, we analyzed the presence of genome-wide epistasis using the binary test implemented in the PLINK program.Results. We identified several genomic regions showing evidence of genome-wide association (P < 1 ؋ ؊5). In the replication analysis, we identified KLF12 SNP rs1324913 as the most strongly associated SNP (P ‫؍‬ 0.01). In our study, we observed that this SNP showed higher significance than PTPN22 SNP rs2476601, in both the genome-wide association studies and the replication analyses. Furthermore, the integration of our data with those from previous genome-wide association studies showed that KLF12 and PTPRT are the unique loci that are commonly associated in 3 different studies (P ‫؍‬ 0.004 and P ‫؍‬ 0.002 for KLF12 in the Wellcome Trust Case Control Consortium study and the Brigham and Women's Rheumatoid Arthritis Sequential Study genome-wide association study, respectively). The genome-wide epistasis analysis identified several SNP pairs close to significance after multiple test correction.Conclusion. The present genome-wide association study identified KLF12 as a new susceptibility gene for RA. The joint analysis of our results and those from previous genome-wide association studies showed genomic regions with a higher probability of being genuine susceptibility loci for RA.Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases in the world (1). In RA, chronic inflammation of the synovial joints leads to progressive articular damage, which can result in major functional disability (2). The etiology of RA is unknown, but several family aggregation and twin studies (3,4) clearly demonstrate a heritable component of the disease. Part of this genetic component of susceptibility has been consistently associated with the HLA class II locus variation. The remaining 50-75% of the genetic component includes several other genomic regions that are more difficult to identify due to their lower penetrance or more complex models of action (5,6).

Recent genome-wide association studies (GWASs) have identified >20 new loci associated with the susceptibility to psoriasis vulgaris (PsV) risk. We investigated the association of PsV and its main clinical subphenotypes with 32 loci having previous genome-wide evidence of association with PsV (P < 5e-8) or strong GWAS evidence (P < 5e-5 in discovery and P < 0.05 in replication sample) in a large cohort of PsV patients (n = 2005) and controls (n = 1497). We provide the first independent replication for COG6 (P = 0.00079) and SERPINB8 (P = 0.048) loci with PsV. In those patients having developed psoriatic arthritis (n = 955), we found, for the first time, a strong association with IFIH1 (P = 0.013). Analyses of clinically relevant PsV subtypes yielded a significant association of severity of cutaneous disease with variation at LCE3D locus (P = 0.0005) in PsV and nail involvement with IL1RN in purely cutaneous psoriasis (PsC, P = 0.007). In an exploratory analysis of epistasis, we replicated the previously described HLA-C-ERAP1 interaction with PsC. Our findings show that common genetic variants associated with a complex phenotype like PsV influence different subphenotypes of high clinical relevance.