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Background: Baricitinib (BARI) or Tofacitinib (TOFA) were the first Janus Kinase Inhibitors (JAKi) to be marketed in rheumatoid arthritis (RA). Concerns regarding venous thromboembolism (VTE) risk have emerged during the past years. The aim of the study was to compare the baseline characteristics of patients initiating BARI or TOFA in RA before versus after European Medicine Agency (EMA)’s VTE warnings and to compare real-world persistence with these two drugs. Methods: In this multicentric cohort study, RA patients initiating BARI or TOFA were included from October 2017, date of BARI marketing authorization in France, to September 2020. Baseline characteristics regarding VTE risk were compared (before vs. after May 2019) by using pre-specified statistical tests. Comparison of persistence was assessed by using propensity-score methods. Results: 232 patients were included; 155 with BARI and 77 with TOFA. Baseline characteristics of patients regarding VTE risk factors were not statistically different when Janus Kinase inhibitor (JAKi) was initiated before vs. after EMA’s warnings although a trend towards a lower proportion of VTE history was observed. Five VTE events occurred, four with BARI, one with TOFA. Cumulative persistence rate at 2 years was similar between BARI and TOFA: HR 0.96; 95% Cl: 0.52 to 1.74; p = 0.89. Conclusions: Our study did not show a significant change in patients characteristics starting a JAKi after the EMA’s warnings, probably due to a lack of power. Though, the lower proportion of VTE history in patients after May 2019 suggests that rheumatologists have taken into account the potential VTE risk. These results need to be confirmed by further evidence.

Objectives To evaluate the characteristics of patients (pts) with PsA treated by ustekinumab (UST) or secukinumab (SEK) and to compare real-world persistence of UST and SEK in PsA. Methods In this retrospective, national, multicentre cohort study, pts with PsA (CASPAR criteria or diagnosis confirmed by the rheumatologist) initiating UST or SEK with a follow-up ≥6 months were included from January 2011 to April 2019. The persistence between SEK and UST was assessed after considering the potential confounding factors by using pre-specified propensity-score methods. Causes of discontinuation and tolerance were also collected. Results A total of 406 pts were included: 245 with UST and 161 with SEK. The persistence rate was lower in the UST group compared with the SEK group [median persistence 9.4 vs 14.7 months; 26.4% vs 38.0% at 2 years; weighted hazard ratio (HR) = 1.42; 95% CI: 1.07, 1.92; P =0.015]. In subgroup analysis, the persistence rate of SEK associated with MTX was significantly higher than that of UST associated with MTX: HR = 2.20; 95% CI: 1.30, 3.51; P =0.001, in contrast to SEK vs UST monotherapy: HR = 1.06; 95% CI: 0.74, 1.53; P =0.75. Discontinuation due to inefficacy was reported in 91.7% (SEK) and 82.4% (UST) of pts. Discontinuation due to an adverse event was reported in 12.2% (SEK) and 7.7% (UST) of pts. Conclusion In this first study comparing UST and SEK, the persistence of SEK was higher than that of UST in PsA. In subgroup analysis, this difference was only found in association with MTX.

(1) Background: To determine which factors are associated with the volume of monosodium urate (MSU) crystal deposition quantified by dual-energy computed tomography (DECT) in urate-lowering therapy (ULT)-naive gout patients. (2) Methods: In this multicenter cross-sectional study, DECT scans of knees and feet/ankles were prospectively obtained from ULT-naive gout patients. Demographic, clinical (including gout history and comorbidities), and biological data were collected, and their association with DECT MSU crystal volume was analyzed using bivariate and multivariate analyses. A second bivariate analysis was performed by splitting the dataset depending on an arbitrary threshold of DECT MSU volume (1 cm3). (3) Results: A total of 91 patients were included. In the bivariate analysis, age (p = 0.03), gout duration (p = 0.003), subcutaneous tophi (p = 0.004), hypertension (p = 0.02), diabetes mellitus (p = 0.05), and chronic heart failure (p = 0.03) were associated with the total DECT volume of MSU crystal deposition. In the multivariate analysis, factors associated with DECT MSU volumes &ge, 1 cm3 were gout duration (odds ratio (OR) for each 10-year increase 3.15 (1.60, 7.63)), diabetes mellitus (OR 4.75 (1.58, 15.63)), and chronic heart failure (OR 7.82 (2.29, 31.38)). (4) Conclusion: Specific comorbidities, particularly chronic heart failure and diabetes mellitus, are more strongly associated with increased MSU crystal deposition in knees and feet/ankles than gout duration, regardless of serum urate level.

Background: Dual-energy computed tomography (DECT) is being considered as a non-invasive diagnostic and characterization tool in calcium crystal-associated arthropathies. Our objective was to assess the potential of DECT in distinguishing between basic calcium phosphate (BCP) and calcium pyrophosphate (CPP) crystal deposition in and around joints in vivo. Methods: A total of 13 patients with calcific periarthritis and 11 patients with crystal-proven CPPD were recruited prospectively to undergo DECT scans. Samples harvested from BCP and CPP calcification types were analyzed using Raman spectroscopy and validated against synthetic crystals. Regions of interest were placed in BCP and CPP calcifications, and the following DECT attenuation parameters were obtained: CT numbers (HU) at 80 and 140 kV, dual-energy index (DEI), electron density (Rho), and effective atomic number ( Zeff). These DECT attenuation parameters were compared and validated against crystal calibration phantoms at two known equal concentrations. Receiver operating characteristic (ROC) curves were plotted to determine the highest accuracy thresholds for DEI and Zeff. Results: Raman spectroscopy enabled chemical fingerprinting of BCP and CPP crystals both in vitro and in vivo. DECT was able to distinguish between HA and CPP in crystal calibration phantoms at two known equal concentrations, most notably by DEI (200 mg/cm3: 0.037 ± 0 versus 0.034 ± 0, p = 0.008) and Zeff (200 mg /cm3: 9.4 ± 0 versus 9.3 ± 0, p = 0.01) analysis. Likewise, BCP calcifications had significantly higher DEI (0.041 ± 0.005 versus 0.034 ± 0.005, p = 0.008) and Zeff (9.5 ± 0.2 versus 9.3 ± 0.2, p = 0.03) than CPP crystal deposits with comparable CT numbers in patients. With an area under the ROC curve of 0.83 [best threshold value = 0.0 39, sensitivity = 90. 9% (81.8, 97. 7%), specificity = 64.6% (50.0, 64. 6%)], DEI was the best parameter in distinguishing between BCP and CPP crystal depositions. Conclusion: DECT can help distinguish between crystal-proven BCP and CPP calcification types in vivo and, thus, aid in the diagnosis of challenging clinical cases, and in the characterization of CPP and BCP crystal deposition occurring in osteoarthritis.

Resume Les rhumatismes microcristallins sont des pathologies tres frequemment rencontrees chez le sujet âge, essentiellement sous la forme du rhumatisme a depots de cristaux de pyrophosphate de calcium dihydrate (PPCD) et de la goutte. Ces rhumatismes peuvent se presenter comme des arthrites aigues dont le diagnostic se fait sur l’identification microcristalline par analyse du liquide synovial en microscopie en lumiere polarisee. En l’absence de cette preuve, le diagnostic reste un defi que des techniques emergentes d’imagerie peuvent aider a relever. La prise en charge anti-inflammatoire theorique repose sur des traitements conventionnels que sont la colchicine, les anti-inflammatoires non steroidiens et les corticoides. Utilises chez des sujets âges presentant frequemment des comorbidites, ils presentent des precautions d’emploi et des contre-indications, ce qui fait que les therapeutiques anti-interleukine 1 sont parfois envisagees. Seule la goutte possede pour l’heure un traitement de fond mais des strategies peuvent egalement etre envisagees dans le cadre des formes chroniques de PPCD qui peuvent revetir des presentations tres polymorphes.

Tumour necrosis factor alpha (TNFα) is a key cytokine in inflammatory rheumatic diseases but is also implicated in multiple sclerosis (MS) where TNFα is elevated in demyelinating plaques. However, TNFα inhibitors (TNFi) have opposite effects: they have revolutionised the treatment of chronic rheumatic diseases but may cause flares of MS.1 Several studies have suggested an association between TNFi use and occurrence of demyelinating disorders.2 3 Their incidence is estimated up to 4% after 18 months of treatment in a recent prospective study with systematic neurological examination before and after treatment initiation.4 In addition, two TNF receptor superfamily 1 ( TNFRSF1A ) single nucleotide polymorphisms, (SNPs) rs1800693 and rs4149584 (TNFRSF1A R92Q), have been shown to increase the risk of developing MS.5 The rs1800693*G allele leads to a dysfunctional TNFα soluble receptor that inhibits TNFα signalling.6 Rare variants of TNFRSF1A locus have also been implicated …

Background Ultrasonography (US) and dual-energy computed tomography (DECT) can assess urate burden in gout. The objective of this study was to compare the quantification of urate deposition provided by US to the one provided by DECT. Methods Patients with a diagnosis of gout were prospectively recruited to undergo quantification of urate deposition using US and DECT. US examination for tophi and the double contour (DC) sign was performed on the knees and feet and corresponding DECT scans provided volumes of tophi and of overall urate deposition. The primary endpoint was the intra-class correlation coefficient (ICC) of the volume of the index tophus measured by US and DECT and its 95% confidence interval (CI 95%). Results Of the 64 patients included, 34 presented with at least one tophus on US. DECT inter-reader agreement for urate deposition was perfect with an ICC of 1 (1–1) and good for the measurement of the index tophus with an ICC of 0.69 (0.47–0.83). The ICC for the measurement of the index tophus between the two techniques was poor with a value of 0.45 (0.1–0.71). The average ratio between the index tophi volume as assessed by DECT and US was 0.65. The number of DC-positive joints did not correlate with DECT volume of overall deposits (Spearman correlation coefficient of 0.23). Conclusions DECT measurements of tophi give smaller volumes to the same tophi measured with US, and US signs of urate deposition in joints do not correlate with overall DECT volumes of extra-articular deposition. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1381-2) contains supplementary material, which is available to authorized users.

ObjectivesLittle data are available regarding the rate and predicting factors of serious infections in patients with rheumatoid arthritis (RA) treated with abatacept (ABA) in daily practice. We therefore addressed this issue using real-life data from the Orencia and Rheumatoid Arthritis (ORA) registry.MethodsORA is an independent 5-year prospective registry promoted by the French Society of Rheumatology that includes patients with RA treated with ABA. At baseline, 3 months, 6 months and every 6 months or at disease relapse, during 5 years, standardised information is prospectively collected by trained clinical nurses. A serious infection was defined as an infection occurring during treatment with ABA or during the 3 months following withdrawal of ABA without any initiation of a new biologic and requiring hospitalisation and/or intravenous antibiotics and/or resulting in death.ResultsBaseline characteristics and comorbidities: among the 976 patients included with a follow-up of at least 3 months (total follow-up of 1903 patient-years), 78 serious infections occurred in 69 patients (4.1/100 patient-years). Predicting factors of serious infections: on univariate analysis, an older age, history of previous serious or recurrent infections, diabetes and a lower number of previous anti-tumour necrosis factor were associated with a higher risk of serious infections. On multivariate analysis, only age (HR per 10-year increase 1.44, 95% CI 1.17 to 1.76, p=0.001) and history of previous serious or recurrent infections (HR 1.94, 95% CI 1.18 to 3.20, p=0.009) were significantly associated with a higher risk of serious infections.ConclusionsIn common practice, patients treated with ABA had more comorbidities than in clinical trials and serious infections were slightly more frequently observed. In the ORA registry, predictive risk factors of serious infections include age and history of serious infections.

OBJECTIVES--To assess the vascular involvement in labial salivary gland (LSG) from patients with rheumatoid vasculitis (RV). METHODS--Forty seven patients with rheumatoid arthritis (RA) took part in a prospective study. Among them, 12 had proven RV. LSG biopsy was performed after local anaesthesia. RESULTS--Histological appearance of inflammatory vascular damage was observed in all but one patient with proven RV (92%). Inflammatory vascular involvement was also identified in LSG biopsy of seven patients with RA (20%) and only one patient in the control group (8%). A second specimen of LSG was studied after a mean treatment period of six months and failed to show any feature of inflammatory vascular involvement in three of the five cases that were analysed. CONCLUSIONS--The study emphasises the high incidence of immunopathological features of microvascular damage in patients with RV. LSG biopsy is minimally invasive and may be a potential useful tool for the diagnosis of RV especially when skin lesions are absent or impossible to biopsy. The assessment of the predictive value of positive LSG biopsy in RA requires a long term prospective study.