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Objectives: To investigate the ex vivo effect of the JAK1/2 inhibitor baricitinib on expression of pro-inflammatory mediators in rheumatoid arthritis (RA) fibroblast like synoviocytes (FLS) stimulated with TNFα, IL-1β and oncostatin M (OSM), and in RA synovial membrane cells (SMCs)., Methods: RA and osteoarthritis (OA) SMCs, were isolated from arthroplasty specimens of RA (n=8) and OA (n=8) patients, respectively, using enzymatic digestion followed by cell propagation to obtain RA (n=5) and OA (n=3) FLS. Normal FLS and normal human foreskin fibroblasts (HSF) were purchased from commercial sources. Fibroblasts were stimulated with cytokines with or without baricitinib. RA SMCs were cultured in the presence of baricitinib without stimulation. JAK/STAT activation and levels of mRNA and proteins of the various inflammatory cytokines (IL-6, IL-8, MCP-1, RANTES and IP-10) were determined by qPCR, ELISA and MSD., Results: Baricitinib inhibited OSM-induced JAK signalling in RA synovial fibroblasts and effectively suppressed subsequent expression of the proinflammatory mediators IL-6, MCP-1 and IP-10. However, baricitinib was not effective in altering levels of spontaneously released TNFα, IL-6 and IL-8 in RA SMC. Although both TNFα and IL-1β signal independently of the JAK/STAT pathway, in HSF, but not in RA FLS, baricitinib significantly inhibited TNFα- and IL-1β-induced MCP-1 and IP-10 protein levels in a dose dependent manner. Furthermore, baricitinib did not inhibit TNFα- and IL-1β-induced expression of IL-6, IL-8 and MCP-1 in RA FLS., Conclusions: These findings are consistent with known signalling pathways employed by OSM, TNFα and IL-1β, but our data suggest that in HSF, baricitinib may have anti-inflammatory effects via downstream modulation of cytokines and chemokines produced in response to TNFα or IL-1β.

Objectives: Spondyloarthritis (SpA) is often diagnosed late in the course of the disease and improved methods for early diagnosis are required. We have tested the ability of genetic profiling to diagnose axial SpA (axSpA) as a whole group, or ankylosing spondylitis (AS) alone, in a cohort of chronic back pain patients., Methods: 282 patients were recruited from centres in the United Kingdom, Germany, Taiwan, Canada, Columbia and Turkey as part of the ASAS classification criteria for axSpA study (ASAS cohort). Subjects were classified according to the ASAS axSpA criteria, and the modified New York Criteria for AS. Patients were genotyped for ~200,000 immune-mediated disease SNPs using the Illumina Immunochip., Results: We first established the predictive accuracy of genetic data comparing 9,638 healthy controls and 4,428 AS cases from the homogenous International Genetics of AS (IGAS) Consortium Immunochip study which showed excellent predictive power (AUC=0.91). Genetic risk scores had lower predictive power (AUC=0.83) comparing ASAS cohort axSpA cases meeting the ASAS imaging criteria with IGAS controls. Comparing genetic risk scores showed moderate discriminatory capacity between IGAS AS and ASAS imaging positive cases (AUC 0.67±0.05), indicating that significant differences in genetic makeup exist between the cohorts., Conclusions: In a clinical setting of referred back pain patients suspected to have axial SpA we were unable to use genetic data to construct a predictive model better than that based on existing clinical data. Potential confounding factors include significant heterogeneity in the ASAS cohort, possibly reflecting the disease heterogeneity of axSpA, or differences between centres in ascertainment or classification performance.

Objectives: To assess the extent of coexistence of inflammatory back pain (IBP) with fibromyalgia (FM) features in patients with spondyloarthritis (SpA), and to assess the degree of overlap of FM tender points (TeP) and enthesitis sites (ES) in patients with SpA., Methods: We evaluated 61 consecutive patients who presented with IBP. Anterior and posterior anatomic diagrams were used as an aid to record assessments of TeP typically seen in FM and ES., Results: Of the patients assessed (n=61), 60 patients (97.9%) fulfilled criteria for IBP (male: female=17:43 (28.3%:71.7%); mean age=47.9 years (SD=11.5) and were included in the analysis. Of those who returned the questionnaire (n=47 (78.3%), 76.6% had onset of symptoms at ≤40 years (mean age=33.5±12.5 years), 87.2% had back pain of ≥3 months duration, 91.5% had morning stiffness (mean duration=70±66 minutes), and 60% showed improvement of pain with exercise. Eating disorders were reported by 21.3% of subjects, and stress was identified as a disease trigger by 40.4% of the respondents. Other symptoms related to FM were reported by 68.1% of the interviewed subjects. Of the 60 patients assessed, 18 (30%) fulfilled the clinical criteria for FM (at least 11 out of 18 TeP). Using regression analysis, a significant correlation was identified between FM TeP and ES., Conclusions: One third of patients with IBP fulfilled the criteria for FM. There is a significant degree of overlap between FM TeP and ES in patients with IBP.

Objectives: Psoriatic arthritis (PsA) has been defined as a systemic, chronic, inflammatory arthritis, usually seronegative for rheumatoid factor (RF), associated with cutaneous psoriasis. The exact prevalence of PsA is unknown and its estimation has been difficult, partly due to the lack of a widely accepted classification criteria. Agreed and validated criteria will facilitate comparison between centres and different countries in the areas of epidemiology, outcome studies and therapeutic trials. A number of classification criteria have been published by Moll & Wright (M & W), Bennett's, Vasey and Espinoza (V & E), Fournié's, European Spondyloarthropathy Study Group (ESSG), McGonagle, Gladman and most recently, the CASPAR Study Group. In this paper, we present an audit aiming to assess which of these criteria performs better in clinical practice., Methods: Sixty-nine (69) patients with evidence of PsA were seen in the clinic as regular outpatients and were assessed as to whether they fulfil any of the 6 existing criteria for PsA: M & W, Bennett's, V & E, Fournié's, ESSG and CASPAR criteria. All items included in the 6 sets of criteria were recorded for each patient based on interview, clinical examination and scrutiny of clinical medical records. By comparing the criteria between themselves as well as the items used in each one of them we tried to assess which one of the criteria was performing best., Results: A total of 69 patients (M/F=24/45; mean age 46.4 years (+/-20.3), and delay in diagnosis of 3.4 years (+/-4.1) was assessed. From those, 9 patients did not fulfil any criteria and excluded from the analysis. From the remaining 60 patients [M/F=21/39; (age 48+/-15.3)], 21 patients (35%) fulfilled all 6 sets of criteria. The remaining 39 patients (M/F=41/59 %; age 47+/-14.9) were further analysed with regards to the feature that did not enable concordance. From those 39 patients, Bennett's criteria were positive in only 4/39 (10.2%), M & W criteria were positive in 12/39 (30.7%), ESSG criteria in 17/39 (43.5%), V & E criteria were positive in 18/39 (46.1%), Fournié's criteria were positive in 31/39 (79.4%) and CASPAR criteria in 35/39 (89.7%). By including family history of psoriasis in the criteria, 11/39 patients (28.2%), who did not fulfil M & W or V & E due to lack of family history of psoriasis as item, met the CASPAR criteria. In addition, some patients who did not fulfil the M & W criteria, since RF positive (7/39; 17.9%), were able to satisfy the CASPAR criteria., Conclusions: Family history of psoriasis is the main advantage of the new CASPAR Criteria over M & W and V & E. In addition, using the CASPAR criteria, it is possible to make a diagnosis of PsA in a patient who develops inflammatory articular disease even if with RF positive and polyarticular symmetrical arthritis. It is also important to have these classification criteria for the development of recommendations for the optimal treatment of patients with PsA. We believe that the CASPAR criteria, which are simple and easy to use, have high potential to be introduced as the universal classification criteria for PsA. However, further study of the validation of these new criteria is required.