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ObjectiveThere is limited experience regarding the use of biological disease-modifying antirheumatic drug (bDMARD) and JAK inhibitor (JAKi) for the management of immune checkpoint inhibitors (ICI)-induced inflammatory arthritis. We aimed to assess their efficacy and safety in this setting.MethodsUsing the Club Rhumatismes and Inflammation French network, we conducted a multicentre, retrospective, observational study of patients with cancer diagnosed with inflammatory arthritis under ICI(s) and treated with bDMARD or JAKi. Clinical data were collected using a standardised case report form.ResultsTwenty patients (60% men, median age 69.5 years) were included, with rheumatoid arthritis (RA)-like (n=16), polymyalgia rheumatica-like (n=2) or psoriatic arthritis-like (n=2) clinical presentation. Two patients had pre-existing RA. 90% were treated with glucocorticoids as first-line therapy and 60% received methotrexate prior to bDMARD or JAKi. Anti-interleukin-6 receptor (IL-6R) therapy was used in 13/20 patients (65%), leading to clinical improvement in 11/13 patients (85%), but one patient experienced intestinal perforation and cancer progression was noticed in 6/13 patients (46%). Tumour necrosis factor inhibitors were used in 5/20 patients (25%), with improvement in 4/5 patients (80%) and cancer progression was observed in 3/5 patients (60%). Two infections (diverticulitis and pneumonitis) were reported. Anakinra, baricitinib and ustekinumab were each used in one patient. Median duration of the bDMARD or JAKi was 17 weeks.ConclusionAnti-IL-6R therapy is currently the most common strategy in patients with ICI-induced inflammatory arthritis and insufficient response to glucocorticoids and methotrexate, leading to improvement in >80%. Overall, cancer progression occurred in about half of patients and whether the bDMARD/JAKi impacted the tumour response remains to be determined.

Introduction La réponse vaccinale chez les patients atteints de maladies auto-immunes et inflammatoires peut être fortement impactée sous certains traitements de fond, tels que le RTX. À ce jour, peu de données sont disponibles concernant les JAK inhibiteurs (JAKi), et aucune en lien avec la vaccination anti-SARS-CoV-2. L’objectif de cette étude était d’étudier la réponse vaccinale anti-SARS-CoV-2 chez des patients sous JAKi. Patients et méthodes Dans cette étude ancillaire du registre MAJIK-SFR (NCT04602091), les patients toujours sous anti-JAKi au moment de la vaccination et ayant eu une sérologie anti-SARS-CoV-2 effectuée au moins 2 semaines après un schéma vaccinal complet (2 injections du vaccin Pfizer, Moderna ou AstraZeneca, ou 1 injection du vaccin Janssen, ou infection COVID-19 suivi d’une injection de n’importe quel vaccin). Les taux d’anticorps IgG ou totaux anti-protéine spike (S1, S1/S2 ou RBD) ont été détectés à l’aide de kits commerciaux utilisant majoritairement la technique d’immunoanalyse par chimiluminescence, ou dans 4 cas par ELISA ou enzyme linked fluorescence assay (ELFA). Le patient était considéré répondeur si le taux d’anticorps détecté était ≥ au seuil de positivé du kit. Les caractéristiques des patients ont été comparées entre les répondeurs et non-répondeurs afin d’identifier les facteurs associés a la non-réponse. Résultats Cent treize patients ont été inclus (98 [86,7 %] atteints de PR, 15 [13,4 %] de PsA) dont 56 (49,6 %) sous baricitinib, 30 (26,5 %) sous tofacitinib et 27 (23,9 %) sous upadacitinib. Quatre-vingt-dix-sept (85,8 %) patients ont reçu une vaccination par vaccin à ARNm (Pfizer ou Moderna). Neuf patients avaient eu une infection COVID avant la vaccination. Cinq patients ont reçu une 3e dose. La réponse vaccinale a été évaluée en moyenne 8,7 semaines (±5,2) après la dernière injection. Le taux de séroconversion était de 88,5 %. Le taux de non-réponse était plus élevé sous upadacitinib (n = 7/27, 25,9 %, p = 0,013) comparé au baricitinib (n = 5/56, 8,9 %) ou tofacitinib (n = 1/30, 3,3 %). Les non-répondeurs étaient plus âgés que les répondeurs (p = 0,02), mais l’âge moyen à la vaccination était similaire pour chaque JAKi. Sous barictinib et tofacitinib les non-répondeurs avaient tous ≥ 65 ans ; 4 des 7 non-répondeurs sous upadacitinib avaient moins de 65 ans. L’intervalle entre la dernière injection et la sérologie était légèrement plus long chez les non-répondeurs (11,25 ± 5,94 vs 8,32 ± 5,01, p = 0,099). Aucun autre paramètre (utilisation concomitante de MTX ou corticostéroïdes, dose de JAKi, activité de la maladie, type de vaccin) n’était associé à une non-réponse. Un antécédent de traitement par RTX (n = 18, 15,9 %) n’avait pas non plus d’impact sur la réponse vaccinale ; néanmoins, la dernière injection datait de ≥ 6 mois avant la vaccination chez tous les patients. Conclusion Le taux de séroconversion après vaccination anti-SARS-CoV-2 chez les patients traités par JAKi reste élevé (88,5 %). Cependant, la non-réponse peut survenir principalement chez les patients âgés ≥ 65 ans. De plus, l’upadacitinib était associé à un taux de non-réponse plus élevé (25,9 %). Ces résultats doivent être confirmés mais suggèrent que chez les patients sous JAKi de ≥ 65 ans ou traités par upadacitinib, une évaluation sérologique pourrait être discuter pour guider la décision clinique (3e dose de vaccin et/ou vaccination familiale). L’évaluation de la réponse immunitaire cellulaire chez les non-répondeurs sera également intéressante pour déterminer si une autre forme d’immunité peut avoir été acquise.

Objectives The primary objective of this study was to assess the stressful life events preceding the onset of symptoms in RA. The secondary objectives were to assess how early RA patients perceive stress and cope with stressors. Methods A case–control study was performed, comparing patients recently diagnosed with RA to age- and gender-matched control subjects recently hospitalized for an unplanned surgical procedure not known to be influenced by stress. The Social Readjustment Rating Scale assessed the cumulative stress induced by stressful life events in the year preceding the onset of symptoms. Coping strategies, stress and anxiety symptoms were evaluated using validated psychological scales. Results Seventy-six subjects were included in each group. The mean Social Readjustment Rating Scale score was twice as high in cases compared with controls [respectively, 167.0 (172.5) vs 83.3 (124.4), P Conclusion Patients with early RA reported more life events in the year preceding the onset of symptoms than controls. Gender specificities were found with a significant association between cumulative stress and RA only in women.

Objective To explore acceptance and retention rate of biosimilar CT-P13 after switching from originator infliximab (OI) in patients with various rheumatic diseases. Methods Patients with stable rheumatoid arthritis (RA), ankylosing spondylitis (AS) or psoriatic arthritis (PsA) under OI were proposed to switch to CT-P13 at the same regimen. A prospective cohort of infliximab-naive patients beginning CT-P13 and a retrospective cohort of patients treated with OI were used as controls. The primary outcome was to evaluate the retention rate of CT-P13. Secondary outcomes were the switch acceptance rate, reasons of failure and safety. Results Switch was proposed to 100 patients and accepted by 89 of them (63 AS, 12 PsA and 14 RA). After a median follow-up of 33 weeks, 72% of patients were still treated with CT-P13. This retention rate was significantly lower than the one found in our retrospective and prospective control cohorts: 88% and 90% respectively (P-value = 0.0002). Within patients who asked to be reswitched to OI, 13/25 (52%) presented clinical disease activity, one developed serum sickness and 11 (44%) presented no objective activity. A subanalysis excluding these 11 patients abrogated difference in retention rates between the 3 cohorts (P-value = 0.453). After reswitching to OI, patients without objective disease activity claimed to recover original efficacy. Conclusions Retention rate was lower after switching from OI to CT-P13 compared to our control cohorts. However, this difference faded after excluding patients without objective clinical activity, suggesting a reluctance of patients to the switch and a negative perception of the biosimilar.

Resume Objectifs Etudier l’acceptabilite et le taux de maintien de l’infliximab biosimilaire CT-P13 (Inflectra©) apres switch a partir de l’infliximab original (IO) chez des patients atteints de rhumatismes inflammatoires. Methodes Il a ete propose a des patients atteints de polyarthrite rhumatoide (PR), de spondylarthrite ankylosante (SA) ou de rhumatisme psoriasique (RhPso) controles sous IO, un switch pour le CT-P13 en poursuivant le meme schema therapeutique. Une cohorte prospective de patients naifs d’infliximab debutant le CT-P13 et une cohorte historique de patients traites par IO ont ete utilisees comme groupes temoins. L’objectif principal etait d’etudier le taux de maintien du CT-P13. Les objectifs secondaires etaient l’etude de l’acceptabilite, des raisons d’echec du switch et de la tolerance. Resultats Le switch a ete propose a 100 patients et accepte par 89 d’entre eux (63 SA, 12 RhPso et 14 PR). Apres un suivi median de 33 semaines, 72 % des patients etaient toujours traites par CT-P13. Ce taux de maintien etait significativement plus faible que celui retrouve dans les cohortes temoins historique et prospective : 88 % et 90 % respectivement (p = 0,0002). Parmi les patients demandant un retour a l’IO, 13/25 (52 %) presentaient une activite clinique de leur maladie, un patient a presente une maladie serique et 11 (44 %) ne presentaient pas d’activite objective. Une analyse excluant ces 11 patients faisait disparaitre la difference de taux de maintien entre les 3 cohortes (p = 0,453). Apres retour a l’IO, les patients sans activite clinique objective retrouvaient tous leur etat anterieur. Conclusion Le taux de maintien etait significativement plus faible apres le switch de l’IO vers le CT-P13 par rapport aux cohortes temoins. Cependant, cette difference disparaissait apres exclusion des patients sans activite clinique objective, suggerant une reticence des patients pour le switch et une perception negative du biosimilaire.

International audience; Objective : To study acceptance rate and factors influencing acceptance of the switch from originator etanercept (Enbrel©) to biosimilar etanercept (SB4, Bénépali©) in patients with rheumatic disease.Methods : Patients with a well-controlled rheumatic disease consulting in our rheumatology department were offered the switch for SB4. After oral and written information concerning biosimilar, free choice to accept the switch was left to the patients. The main outcome was primary switch acceptance rate defined by switch acceptance during the initial consult. Real switch adherence, socio-cultural factors and beliefs influencing switch acceptance rate were retrieved during a telephonic interview at distance from the consultation.Results : Fifty-two patients were eligible for the switch: 32 (62%) with spondyloarthritis and 20 (38%) with rheumatoid arthritis. The primary acceptance rate was 92% (48/52). Patients refusing the switch were more likely to report a bad opinion on generic drugs (100% vs 11%, p

To date, all available data regarding the switch from bio-originator to its biosimilar are reassuring, and the switch has been recommended as a shared patient–physician decision in recent consensus-based recommendations.1 In particular, the Norway's infliximab switching study (NOR-SWITCH study), a 52-week randomised double-blind trial, strongly supports the efficacy and safety of the switch from originator infliximab (OI) to its biosimilar CT-P13 in patients with a stable disease.2 However, long-term follow-up data are required to confirm the efficacy and safety of the switch. In a previous real-life study, we demonstrated a high acceptance of 89% (89/100) and a 72% (64/89) retention rate after a median follow-up of 33 weeks in a cohort of patients with stable rheumatic diseases switched from OI to CT-P13.3 This retention rate was lower compared with two control cohorts: a historic cohort of 82 patients treated with OI in 2013, and …

This report describes how commercial tubular ceramic membranes, initially designed for liquid filtration, can be modified to provide the core separation components of a first stage of flue gas treatment and enrichment in post-combustion CO2 separation. Commercially available tubular NanoFiltration (NF) ceramic membranes were turned into a membrane for CO2 separation by a two-step process including additional ceramic coating and chemical grafting. The combination of ceramic coating and chemical grafting drastically modify the membrane properties and turn the membrane initially designed for liquid filtration into a membrane that displays CO2 vs N2 selectivity at the opposite of Knudsen-based selectivity, with a CO2:N2 ideal selectivity of 2.3. A second step of this study addressed the reduction of membrane cost, by starting with a low ultrafiltration (UF) 200 nm ceramic support specifically manufactured for this application in place of a NF membrane. After successful coating of a 5 nm and a 1 nm ceramic membranes, this membrane, grafted with a commercial fluorosilane molecule was tested in pure gas permeation of CO2 and N2, with an ideal selectivity CO2:N2=3. Finally, the same membrane, grafted with glymo, was tested against separation of a CO2 (20%):N2 (80%) mixture, and as a function of the permeation stage-cut. A CO2:N2 selectivity of 4 was obtained for a stage-cut of 0.5, and even higher (CO2:N2 selectivity=14) for low stage-cuts usually used for testing dense polymer membranes. These results demonstrate that commercial ceramic porous membranes can be used as starting elements for a first stage of CO2 post-combustion gas cleaning and CO2 enrichment.

Recent work showed that carbon nanotubes could be fabricated into bucky-paper structures as self-supporting membranes and their hydrophobic property used for water desalination by membrane distillation. Carbon nanotube bucky-papers possess very interesting properties such as natural hydrophobicity, high porosity and very high specific surface area, making of them promising candidates for separation applications. However, to inhibit crack formation associated with poor mechanical stability, improved durability structures that retain a high degree of hydrophobicity need to be developed. In this work we chemically modified high purity carbon nanotubes by (i) UV/ozone treatment to create hydroxyl groups and (ii) reacting those groups by substitution with alkoxysilane based groups. The resulting nanotubes presented a silicon content up to 2.5% and the bucky-papers produced had larger contact angle (140° compared to 125°) and liquid entry pressures. We report here on their fabrication and use as membranes in direct contact membrane distillation.

We study the electrostatic and hydrodynamic interactions of colloidal particles in nonpolar solvents. Using blinking optical tweezers, we can extract the screening length, kappa-1, the effective surface potential, |ezeta*|, and the hydrodynamic radius, ah, in a single measurement. We apply this technique to suspensions of polystyrene and poly(methyl methacrylate) particles in hexadecane with soluble charge control agents, aerosol sodium di-2-ethylhexylsulfosuccinate (AOT) and polyisobutylene succinimide (OLOA-1200). We find that the electrostatic interactions of these particles depend sensitively on surface composition as well as on the concentration and chemistry of the charge control agent.

We describe and implement a technique for extracting forces from the relaxation of an overdamped thermal system with normal modes. At sufficiently short time intervals, the evolution of a normal mode is well described by a one-dimensional Smoluchowski equation with constant drift velocity, v, and diffusion coefficient, D. By virtue of fluctuation-dissipation, these transport coefficients are simply related to conservative forces, F, acting on the normal mode: F = k_BT v/D. This relationship implicitly accounts for hydrodynamic interactions, requires no mechanical calibration, makes no assumptions about the form of conservative forces, and requires no prior knowledge of material properties. We apply this method to measure the electrostatic interactions of polymer microspheres suspended in nonpolar microemulsions., Comment: 4 pages, 3 figures

Electrospun carbon nanofibers (CNFs) were prepared by electrospinning of a polyacrylonitrile solution followed by convenient stabilization and carbonization thermal treatments. By observations of scanning electron microscopy, a mat of interlaced continuous submicronic fibers was detected. Characterization by Raman spectroscopy demonstrated the successful preparation of a carbon material and the influence of the heating-treatment temperature on the structure of the resulting CNFs. The novelty of the approach relies in the easy handling of the resulting electrospun mat electrode that does not require addition of any polymer binder or conductive material. This is the first time that electrospun conductive fibers are envisaged as electrode supports for redox enzymes immobilization applied to bioelectrocatalytic O2reduction. The most interesting thing is the remarkable benefit effect of the CNFs on the electrical performances of the electrode which can ascribe to high loading of active enzymes and fast kinetics at the electrode surface. The remarkably intensified current density (∼1 mA cm−2) achieved at the enzymatic CNFs bioelectrode is probably due to the unique nanostructure and surface properties of these nanomaterials that make them promising candidates as enzymatic cathodes in biofuel cell devices.

We combine real-time feature recognition with holographic optical tweezers to automatically trap, assemble, and sort micron-sized colloidal particles. Closed loop control will enable new applications of optical micromanipulation in biology, medicine, materials science, and possibly quantum computation.