Fatigue in teriflunomide-treated patients with relapsing remitting multiple sclerosis in the real-world Teri-FAST study

BACKGROUND: Fatigue is a frequent and disabling symptom of multiple sclerosis (MS) often associated with impaired quality of life (QoL) in patients. Teriflunomide is a once-daily oral immunomodulator used for the treatment of relapsing remitting forms of MS. However, its effect on fatigue is not well known in real life practice. We evaluated the impact of teriflunomide on fatigue in patients with relapsing remitting MS (RRMS) after 2 years of treatment in the real-world Teri-FAST study. METHODS: Teri-FAST was a 2-year, prospective, observational study conducted in France in RRMS patients treated with teriflunomide 14 mg. Fatigue was assessed using the French version of the modified fatigue impact scale (EMIF-SEP). The primary endpoint was the change from baseline in EMIF-SEP score after 2 years of treatment. Secondary endpoints included evaluation of depression (Beck Depression Inventory [BDI]), health-related QoL (Two-Life Scale TLS-QoL 10), self-reported physical activity, and adverse events. RESULTS: 210 eligible patients were included in the study with a mean age of 45.4 years and a mean ± SD Expanded Disability Status Scale score of 1.76 ± 1.43 at baseline. About half (52.4%) of patients had no previous treatment for MS. In the 163 patients who completed at least 1 follow-up visit, the mean change in EMIF-SEP score at Year 2 was -1.54 (95% CI: -4.02, 0.94) indicating that fatigue remained stable. Similarly, there were no changes in depression level and QoL after 2 years of treatment. Physical activity slightly improved with 57% of patients reporting being physically active after 2 years as compared to 46% at baseline. The safety profile of teriflunomide was consistent with that seen during clinical development, and compliance with treatment was high. CONCLUSION: Fatigue scores remained stable in RRMS patients treated with teriflunomide 14 mg over 2 years in real-life setting. Teriflunomide did not negatively impact depression or QoL

Identification de marqueurs cliniques et biologiques associés au développement d'un athérome infa-clinique dans une cohorte de patients présentant un rhumatisme inflammatoire débutant (cohorte VErA)

(i) Évaluer l'athérome infra-clinique dans une cohorte de patients présentant un rhumatisme inflammatoire débutant [polyarthrite rhumatoïde (PR) ou rhumatisme indifférencié (RI)] et (ii) identifier des marqueurs cliniques et biologiques associés à l'apparition de cet athérome. PATIENTS ET MÉTHODES : Étude prospective de 105 patients (82 PR et 23 RI), suivis pour un rhumatisme inflammatoire évoluant initialement depuis moins de 6 mois et non traité. Suivi clinique, biologique et radiologique régulier. Mesures de marqueurs spécifiques de l'inflammation, du stress oxydant, de l'angiogenèse et de la dysfonction endothéliale au début de la maladie. Recherche des facteurs de risque cardiovasculaire classiques. Évaluation de l'athérome infra-clinique, à 7 ans d'évolution, par une mesure de l'épaisseur intima-média (EIM) carotidienne. RÉSULTATS : Les patients ayant une PR présentent, à l'inclusion, des scores d'activité clinique (DAS 44, HAQ) et des taux d'anticorps anti-CCP plus élevés que les RI ; ils sont également plus souvent porteurs de l'épitope partagé HLADRBI et d'un allèle TNFRII 196R. Les analyses univariées révèlent une corrélation entre l'augmentation de l'EIM carotidienne et des facteurs de risque classiques (âge et HTA), des marqueurs d'activité du rhumatisme (nombre d'articulations gonflées, DAS 44, CRP) et des marqueurs plus spécifiques [inflammation systémique (IL-1b), auto-immunité (CD40L, absence d'Ac anti-CCP), stress oxydant (AOPP)]. Le modèle prédictif d'apparition de lésions athéromateuses obtenu associe 2 facteurs de risque (HTA et nombre d'articulations gonflées) et 1 facteur protecteur (traitement par méthotrexate). CONCLUSION : Notre étude analyse pour la 1 ère fois l'athérome infra-clinique dans les rhumatismes inflammatoires débutants et souligne la nécessité d'évaluer et de prendre en charge précocément ces rhumatismes et les facteurs de risque cardiovasculaires classiques associés.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Asymptomatic carotid occlusion in a young HIV-infected patient receiving HAART.

International audienceThe discovery of an asymptomatic and spontaneous internal carotid occlusion in a young HIV-infected patient, without atherosclerosis, asks the question of cardio-vascular disease's mechanism. A pro-atherogenic profile HAART-associated does not fully explain the high cardio-vascular disease's incidence among the HIV infected population. Carotid stenosis and/or thrombophilic conditions are emergent problems among HIV-infected persons

Correlations between carotid IMT, factor VIII activity level and metabolic disturbances: a cardio-vascular risk factor in the HIV positive persons.

International audienceIn the HIV infection, the short time-scale between the HIV-induced cardiovascular events and the onset of antiretroviral therapy elicits a thrombophilic co-factor that worsens the induced atherosclerosis. We compared the factor VIII plasma activity, previously implicated in arterial and venous thrombosis, with a surrogate marker of atherosclerosis, the carotid intima-media thickness, and with the usual atherosclerosis risk factors in 154 HIV infected outpatients. The FVIII plasma activity is significantly associated with the carotid intima-media thickness and, strongly, with blood glucose and triglycerides levels. A raised FVIII plasma activity is an important feature of the metabolic syndrome and a putative co-factor of HAART induced cardiovascular events. Thus the prevention of the HAART-induced cardio-vascular events should probably not be exclusively focused on atherosclerosis but likewise on the thrombus formation process

Premature atherosclerosis in HIV positive patients and cumulated time of exposure to antiretroviral therapy (SHIVA study).

International audienceBACKGROUND: With the advent of antiretroviral therapy regimens in HIV positive patients, it is crucial to consider their long-term benefits to risk ratios. The responsibility of treatment in premature atherosclerosis is not clear. Thus, the aim of this study is to evaluate the impact of exposure to reverse transcriptase inhibitors (nucleosidic and non-nucleosidic) and to protease inhibitors on the cardiovascular status of an entire hospital based cohort of patients. METHODS: 154 patients were included. Using a linear analysis, we sought an association between the cumulative time of exposure to these three classes of antiretroviral drugs and the carotid intima-media thickness measured by ultrasonography and a cardiovascular composite score. RESULTS: The study confirms premature atherosclerosis, which not only correlates with the usual risk factors, such as triglyceride level, but also with protease inhibitor exposure, especially that of lopinavir. Nevertheless as regards current drug exposure, the clinical impact was low: five clinical complications of atherosclerosis and only one out of 35 scintigraphic and ECG exercise tests warranted a coronary angiography which was negative. CONCLUSION: These data should not lead to the rejection of protease inhibitors but should strengthen the prevention of cardiovascular diseases as an integral part of the management of HIV patients

Temporal dynamics of demersal chondrichthyan species in the central western Mediterranean Sea: The case study in Sardinia Island

Occurrence, abundance and size trends of 25 demersal Chondrichthyes (10 Sharks: 3 Carcharhiniformes, 2 Hexanchiformes, 5 Squaliformes; 14 Batoids: 3 Myliobatiformes, 8 Rajiformes, 3 Torpediniformes and 1 Holocephalan: 1 Chimaeriformes) collected from 22 years (1994–2015) of Mediterranean International Trawl Surveys (MEDITS) around Sardinian seas, were given. Data relative to two strata, the continental shelf (10–200 m), the slope (201–800 m), and the overall (10–800 m), were analyzed in order to identify the general species distribution of their habitat preference. From the gathered data it appeared that the shelf was mostly inhabited by batoids while the slope by sharks. Only the small-spotted catshark Scyliorhinus canicula and the thornback skate Raja clavata were equally distributed with high values of occurrence and abundance both in the shelf and in the slope. All the other species showed a preferential distribution only in one stratum (shelf or slope). In general, temporal trends of abundance indexes were stable or increasing in all strata. GAM analysis also confirmed a stable trend. Almost all species displayed stable in size structure analysis, apart from R. brachyura and Dipturus oxyrinchus that showed a statistically increasing trend. Although the investigated chondrichthyan species seemed to display a not alarming status of conservation in Sardinian seas, more investigation should be done to assure a proper management of this threatened resource

Switching from an anti-TNF monoclonal antibody to soluble TNF-receptor yields better results than vice versa: An observational retrospective study of 72 rheumatoid arthritis switchers

International audienceObjectives : To evaluate the benefits for rheumatoid arthritis (RA) patients of switching from one tumor necrosis factor inhibitor (TNFi) to another based on reason for change (primary failure, escape or intolerance) and molecule-switching order.Methods : Between 2000 and 2008, 356 RA patients prescribed a TNFi (infliximab [IFX], etanercept [ETA] or adalimumab [ADA]) and undergoing standardized evaluation were included in this retrospective study. Detailed demographic, clinical and biological data were collected before first biologic use and ≤ 6 months later to evaluate response based on EULAR-criteria. Primary failure, escape or intolerance of first TNFi triggered switch to another TNFi, the response of which was evaluated 6 months later. Propensity score then measured any interaction with baseline variables.Results : Of the 356 RA patients, 38 switched from IFX/ADA to ETA, 26 from ETA to IFX/ADA, and eight from one monoclonal antibody (mAb; IFX/ADA) to another. Clinical parameters for switchers and non-switchers were comparable. Switchers changed therapies because of primary failure (36.1%), escape (33.3%), or intolerance (30.6%), with no difference found in these subgroups. More switchers responded to the second TNFi than the first (P < 0.01), respectively, regardless of switch (ETA to IFX/ADA: 50 vs. 23.1% [P < 0.05]; IFX/ADA to ETA: 57.9 vs. 15.8% [P < 0.001]) or reason for changing. In addition, DAS28 decreased more with the second antagonist (P < 0.001) and regardless of molecules switched (P < 0.01). Survival of the second TNFi was significantly longer with switch from mAb to the soluble receptor than vice versa (P < 0.05).Discussion : Overall, any switching from one TNFi to another, especially mAb to soluble receptor, was often beneficial for RA patients

Additional file 6: of Dysregulation of RasGRP1 in rheumatoid arthritis and modulation of RasGRP3 as a biomarker of TNFα inhibitors

TNF receptor (TNFR)1 and TNFR2 have no effect on RasGRP1 and RasGRP3 gene expression level in T and B cells respectively. Quantitative PCR analysis was performed to measure RasGRP1 and RasGRP3 gene expression levels in T and B cells respectively from three healthy controls. T or B cells were exposed to anti-TNFR1 or anti-TNFR2 neutralizing antibodies without TNFα for 48 hours. The relative expression levels (in arbitrary units (AU)) of RasGRP1 and RasGRP3 were normalized with 18S RNA abundance. Mean ± standard error of the mean were compared using one-way analysis of variance followed by Bonferroni post-hoc test. (TIF 47 kb

Additional file 7: of Dysregulation of RasGRP1 in rheumatoid arthritis and modulation of RasGRP3 as a biomarker of TNFα inhibitors

TNFα has no effect on T cell apoptosis. After T cell negative selection, cells were cultured with or without TNFα for 48 and 72 hours. To measure apoptosis, a fluorescein isothiocyanate (FITC) annexin-V Apoptosis Detection Kit (BD Biosciences, USA) was used. After labeling with FITC annexin-V and propidium iodide (PI), cells were analyzed by flow cytometry within 1 hour. a One representative result of three independent experiments is presented. b Histogram represents the mean ± standard error of the mean (SEM) of percentage of annexin-V positive cells in three independent experiments. Mean ± SEM were compared using Student’s t test. (TIF 1318 kb