Evaluation globale standardisée systématique des rhumatismes inflammatoires chroniques: intérêts et limites

Introduction: National and international recommendations call for an annual standardized systematic holistic review in the management of chronic inflammatory rheumatism (CIR). This includes an assessment of disease activity and severity, as well as patient education on the disease, knowledge of pharmacological and non-pharmacological treatments, adherence to treatment and screening for comorbidities. Our study aims to recall the definition of a holistic review (HR), to present the evidence of their effectiveness and to give an overview of HR practices in France. Methods: A literature review was conducted in the Pubmed database to identify randomized controlled trials (RCTs) or meta-analyses reporting the efficacy of a multidisciplinary intervention in ICR or other chronic diseases. Two online surveys were sent to all rheumatology departments in France and to a sample of independent rheumatologists, with 34 and 19 questions respectively. These questionnaires were used to determine the profile of the responding center/rheumatologist, the existence of an HR and the obstacles or facilitators to its implementation. Results: Literature search yielded 872 articles, 24 of which were finally included: 16 RCTs and 8 meta-analyses. Only 3 articles concerned ICRs, including one meta-analysis of 10 RCTs in rheumatoid arthritis (RA). Of these 3 studies, 2 RCTs in systemic lupus and systemic sclerosis showed a favorable impact of a multidisciplinary approach on SLEDAI and grip strength and mouth opening respectively, while the meta-analysis in RA showed no benefit on disability or disease activity.The questionnaire was answered by 72 centers and 186 rheumatologists. A third of the centers had already implemented a HR during an day hospitalization. 70 % of centers estimated that they managed more than 10 patients per month, devoting an average of 35 minutes of rheumatologist time and 90 minutes of cumulative time for all other healthcare professionals (HCPs) involved in the program. Most of the HCPs involved were nurses (92 %), dieticians (56 %) and physiotherapists (56 %). The main obstacles to setting up a HR were the lack of paramedical resources, lack of economic value and lack of support from treating rheumatologists, while patient motivation was seen as a facilitating factor. Conclusion: Although HR is recommended, there is little evidence of its effectiveness in ICR. Only 36 % of responding centers have implemented such a program. This survey helps to identify the obstacles and facilitators, and to find solutions for extending this practice

Évaluation de l'effet du tofacitinib sur les tissus osseux et adipeux dans la polyarthrite rhumatoïde

Background: Systemic inflammation is the main factor underlying secondary osteoporosis and cardiovascular risk in patients with rheumatoid arthritis (RA). Janus kinase inhibitors (JAKi), such as tofacitinib (Tofa), can control systemic inflammation and may have beneficial effects on bone in various models. This might be due to direct effects on the bone microenvironment and not exclusively based on their anti-inflammatory function. Bone marrow adipocytes (BMAds) are abundant in the bone microenvironment. The effect of JAKi on BMAds is unknown, but evidence suggests that there is competition between human bone marrow-derived stromal cell (hBMSCs) differentiation routes towards BMAds and osteoblasts (Ob) in osteoporosis. JAKi could also have an impact on the visceral adiposity which is associated with the cardiovascular risk.Objectives: The aims of the first part of the PhD were to determine whether Tofa influences BMAds, and Ob derived from hBMSCs and to investigate the potential effects of Tofa on body composition, on bone marrow adipose tissue (BMAT) and bone mineral density (BMD) in RA patients. The aims of the second part of the PhD were to determine the impact of RA on body composition, BMD and BMAT.Methods: To determine the effect of Tofa on cellular commitment, hBMSCs were differentiated to BMAds or Ob for 3 days together with Tofa at 200, 400, or 800 nM and TNFα. This study was also conducted using differentiated BMAds. The impact of Tofa was determined by gene and protein expression analysis and cell density monitoring. In parallel, in a pilot study of 9 RA patients treated with Tofa 5 mg twice a day (NCT04175886), the proton density fat fraction (PDFF) was measured using MRI at the lumbar spine at baseline and at 6 months. The ongoing RAFAT study (NCT05269069) is a case-control study including healthy volunteers matched for sex, age, body mass index, and menopausal status with RA patients.Results: In non-inflammatory conditions, the gene expression of Runx2 and Dlx5 decreased in Ob treated with Tofa (p<0.05). The gene expression of PPARγ2, C/EBPα, and Perilipin 1 were increased compared to controls (p<0.05) in BMAds treated with Tofa. Under inflammatory conditions, Tofa did not change the expression profiles of Ob compared to TNFα controls. In contrast, Tofa limited the negative effect of TNFα on BMAds differentiation (p<0.05). An increase in the density of differentiated BMAds treated with Tofa under TNFα was noted (p<0.001). These findings were consolidated by an increase in PDFF at 6 months of treatment with Tofa in RA patients (46.3 ± 7.0% versus 53.2 ± 9.2% p<0.01).Conclusion: Together, these results suggest a stimulatory effect of Tofa on BMAds commitment and differentiation, which does not support a positive effect of Tofa on bone. The RAFAT study is still ongoing.Contexte : L'inflammation systémique est le principal facteur responsable de l'ostéoporose secondaire et du surrisque cardiovasculaire chez les patients atteints de polyarthrite rhumatoïde (PR). Les inhibiteurs de la Janus kinase (JAKi), tels que le tofacitinib (Tofa), peuvent contrôler l'inflammation systémique et semblent avoir des effets bénéfiques sur le tissu osseux dans différents modèles précliniques. Cela pourrait être dû à des effets directs sur le microenvironnement osseux et ne pas reposer exclusivement sur le contrôle de l'inflammation systémique. Les adipocytes médullaires (BMAds) sont abondants dans le microenvironnement osseux mais l'effet des JAKi sur les BMAds reste méconnu tout en sachant qu'il existe une compétition entre les voies de différenciation des cellules stromales dérivées de la moelle osseuse humaine (hBMSCs) vers les BMAds et les ostéoblastes (Ob) dans l'ostéoporose. Par ailleurs, les JAKi pourraient également avoir un effet sur l'adiposité viscérale, tissu associé au risque cardiovasculaire.Objectifs: Les objectifs de la première partie de la thèse étaient de déterminer si le Tofa influence les BMAds et les Ob dérivés des hBMSCs et d'étudier les effets potentiels du Tofa sur la composition corporelle, l'adiposité médullaire et la densité minérale osseuse chez des patients atteints de PR. Les objectifs de la seconde partie de la thèse étaient de déterminer l'effet de la PR sur la composition corporelle, la densité minérale osseuse et l'adiposité médullaire.Méthodes : Pour déterminer l'effet du Tofa sur l'engagement cellulaire, des hBMSCs ont été différenciées en BMAds ou Ob pendant 3 jours avec des concentrations de Tofa à 200, 400 ou 800 nM et du TNFα pour simuler l'inflammation systémique. Cette étude a également été menée en utilisant des BMAds différenciés. L'effet du Tofa a été déterminé par l'analyse de l'expression des gènes et des protéines et le suivi de la densité cellulaire. En parallèle, dans une étude pilote portant sur 9 patients atteints de PR traités par Tofa 5 mg deux fois par jour (NCT04175886), l'adiposité médullaire a été mesurée par IRM au niveau de la colonne lombaire (PDFF, proton density fat fraction) initialement et après 6 mois de traitement par Tofa. L'étude RAFAT en cours (NCT05269069) est une étude cas-témoins avec des volontaires sains appariés pour le sexe, l'âge, l'indice de masse corporelle et le statut ménopausique à des patients PR.Résultats: Dans des conditions non inflammatoires, l'expression génétique de Runx2 et Dlx5 a diminué chez les Ob traitées par Tofa (p<0,05). L'expression génétique de PPARγ2, C/EBPα et Périlipine 1 était augmentée par rapport aux contrôles (p<0,05) chez les BMAds traités par Tofa. Dans des conditions inflammatoires, Tofa n'a pas modifié les profils d'expression des Ob par rapport aux contrôles TNFα. En revanche, Tofa a limité l'effet négatif du TNFα sur la différenciation des BMAds (p<0,05). Une augmentation de la densité des BMAds différenciées traitées par Tofa sous TNFα a été observée (p<0,001). Ces résultats ont été consolidés par une augmentation du PDFF à 6 mois de traitement par Tofa chez les patients atteints de PR (46,3 ± 7,0% versus 53,2 ± 9,2% p<0,01). Il n'y avait pas de modification de la composition corporelle à 6 mois, notamment de l'adiposité viscérale chez les 9 patients atteints de PR sous Tofa.Conclusion: L'ensemble de ces résultats suggère un effet stimulant du Tofa sur l'engagement et la différenciation des BMAds, ce qui ne soutient pas un effet positif du Tofa sur le tissu osseux. L'étude RAFAT est en cours

Effect of tofacitinib on adipose and bone tissues in rheumatoid arthritis

Contexte : L'inflammation systémique est le principal facteur responsable de l'ostéoporose secondaire et du surrisque cardiovasculaire chez les patients atteints de polyarthrite rhumatoïde (PR). Les inhibiteurs de la Janus kinase (JAKi), tels que le tofacitinib (Tofa), peuvent contrôler l'inflammation systémique et semblent avoir des effets bénéfiques sur le tissu osseux dans différents modèles précliniques. Cela pourrait être dû à des effets directs sur le microenvironnement osseux et ne pas reposer exclusivement sur le contrôle de l'inflammation systémique. Les adipocytes médullaires (BMAds) sont abondants dans le microenvironnement osseux mais l'effet des JAKi sur les BMAds reste méconnu tout en sachant qu'il existe une compétition entre les voies de différenciation des cellules stromales dérivées de la moelle osseuse humaine (hBMSCs) vers les BMAds et les ostéoblastes (Ob) dans l'ostéoporose. Par ailleurs, les JAKi pourraient également avoir un effet sur l'adiposité viscérale, tissu associé au risque cardiovasculaire.Objectifs: Les objectifs de la première partie de la thèse étaient de déterminer si le Tofa influence les BMAds et les Ob dérivés des hBMSCs et d'étudier les effets potentiels du Tofa sur la composition corporelle, l'adiposité médullaire et la densité minérale osseuse chez des patients atteints de PR. Les objectifs de la seconde partie de la thèse étaient de déterminer l'effet de la PR sur la composition corporelle, la densité minérale osseuse et l'adiposité médullaire.Méthodes : Pour déterminer l'effet du Tofa sur l'engagement cellulaire, des hBMSCs ont été différenciées en BMAds ou Ob pendant 3 jours avec des concentrations de Tofa à 200, 400 ou 800 nM et du TNFα pour simuler l'inflammation systémique. Cette étude a également été menée en utilisant des BMAds différenciés. L'effet du Tofa a été déterminé par l'analyse de l'expression des gènes et des protéines et le suivi de la densité cellulaire. En parallèle, dans une étude pilote portant sur 9 patients atteints de PR traités par Tofa 5 mg deux fois par jour (NCT04175886), l'adiposité médullaire a été mesurée par IRM au niveau de la colonne lombaire (PDFF, proton density fat fraction) initialement et après 6 mois de traitement par Tofa. L'étude RAFAT en cours (NCT05269069) est une étude cas-témoins avec des volontaires sains appariés pour le sexe, l'âge, l'indice de masse corporelle et le statut ménopausique à des patients PR.Résultats: Dans des conditions non inflammatoires, l'expression génétique de Runx2 et Dlx5 a diminué chez les Ob traitées par Tofa (p<0,05). L'expression génétique de PPARγ2, C/EBPα et Périlipine 1 était augmentée par rapport aux contrôles (p<0,05) chez les BMAds traités par Tofa. Dans des conditions inflammatoires, Tofa n'a pas modifié les profils d'expression des Ob par rapport aux contrôles TNFα. En revanche, Tofa a limité l'effet négatif du TNFα sur la différenciation des BMAds (p<0,05). Une augmentation de la densité des BMAds différenciées traitées par Tofa sous TNFα a été observée (p<0,001). Ces résultats ont été consolidés par une augmentation du PDFF à 6 mois de traitement par Tofa chez les patients atteints de PR (46,3 ± 7,0% versus 53,2 ± 9,2% p<0,01). Il n'y avait pas de modification de la composition corporelle à 6 mois, notamment de l'adiposité viscérale chez les 9 patients atteints de PR sous Tofa.Conclusion: L'ensemble de ces résultats suggère un effet stimulant du Tofa sur l'engagement et la différenciation des BMAds, ce qui ne soutient pas un effet positif du Tofa sur le tissu osseux. L'étude RAFAT est en cours.Background: Systemic inflammation is the main factor underlying secondary osteoporosis and cardiovascular risk in patients with rheumatoid arthritis (RA). Janus kinase inhibitors (JAKi), such as tofacitinib (Tofa), can control systemic inflammation and may have beneficial effects on bone in various models. This might be due to direct effects on the bone microenvironment and not exclusively based on their anti-inflammatory function. Bone marrow adipocytes (BMAds) are abundant in the bone microenvironment. The effect of JAKi on BMAds is unknown, but evidence suggests that there is competition between human bone marrow-derived stromal cell (hBMSCs) differentiation routes towards BMAds and osteoblasts (Ob) in osteoporosis. JAKi could also have an impact on the visceral adiposity which is associated with the cardiovascular risk.Objectives: The aims of the first part of the PhD were to determine whether Tofa influences BMAds, and Ob derived from hBMSCs and to investigate the potential effects of Tofa on body composition, on bone marrow adipose tissue (BMAT) and bone mineral density (BMD) in RA patients. The aims of the second part of the PhD were to determine the impact of RA on body composition, BMD and BMAT.Methods: To determine the effect of Tofa on cellular commitment, hBMSCs were differentiated to BMAds or Ob for 3 days together with Tofa at 200, 400, or 800 nM and TNFα. This study was also conducted using differentiated BMAds. The impact of Tofa was determined by gene and protein expression analysis and cell density monitoring. In parallel, in a pilot study of 9 RA patients treated with Tofa 5 mg twice a day (NCT04175886), the proton density fat fraction (PDFF) was measured using MRI at the lumbar spine at baseline and at 6 months. The ongoing RAFAT study (NCT05269069) is a case-control study including healthy volunteers matched for sex, age, body mass index, and menopausal status with RA patients.Results: In non-inflammatory conditions, the gene expression of Runx2 and Dlx5 decreased in Ob treated with Tofa (p<0.05). The gene expression of PPARγ2, C/EBPα, and Perilipin 1 were increased compared to controls (p<0.05) in BMAds treated with Tofa. Under inflammatory conditions, Tofa did not change the expression profiles of Ob compared to TNFα controls. In contrast, Tofa limited the negative effect of TNFα on BMAds differentiation (p<0.05). An increase in the density of differentiated BMAds treated with Tofa under TNFα was noted (p<0.001). These findings were consolidated by an increase in PDFF at 6 months of treatment with Tofa in RA patients (46.3 ± 7.0% versus 53.2 ± 9.2% p<0.01).Conclusion: Together, these results suggest a stimulatory effect of Tofa on BMAds commitment and differentiation, which does not support a positive effect of Tofa on bone. The RAFAT study is still ongoing

Body composition in patients with rheumatoid arthritis: a narrative literature review

International audienceThere is growing interest in the alterations in body composition (BC) that accompany rheumatoid arthritis (RA). The purpose of this review is to (i) investigate how BC is currently measured in RA patients, (ii) describe alterations in body composition in RA patients and (iii) evaluate the effect on nutrition, physical training, and treatments; that is, corticosteroids and biologic Disease Modifying Anti-Rheumatic Disease (bDMARDs), on BC in RA patients. The primary-source literature for this review was acquired using PubMed, Scopus and Cochrane database searches for articles published up to March 2021. The Medical Subject Headings (MeSH) terms used were ‘Arthritis, Rheumatoid’, ‘body composition’, ‘sarcopenia’, ‘obesity’, ‘cachexia’, ‘Absorptiometry, Photon’ and ‘Electric Impedance’. The titles and abstracts of all articles were reviewed for relevant subjects. Whole-BC measurements were usually performed using dual energy x-ray absorptiometry (DXA) to quantify lean- and fat-mass parameters. In RA patients, lean mass is lower and adiposity is higher than in healthy controls, both in men and women. The prevalence of abnormal BC conditions such as overfat, sarcopenia and sarcopenic obesity is significantly higher in RA patients than in healthy controls; these alterations in BC are observed even at an early stage of the disease. Data on the effect treatments on BC in RA patients are scarce. In the few studies published, (a) creatine supplementation and progressive resistance training induce a slight and temporary increase in lean mass, (b) exposure to corticosteroids induces a gain in fat mass and (c) tumour necrosis factor alpha (TNFα) inhibitors might be associated with a gain in fat mass, while tocilizumab might be associated with a gain in lean mass. The available data clearly demonstrate that alterations in BC occur in RA patients, but data on the effect of treatments, especially bDMARDs, are inconsistent and further studies are needed in this area

Efficacy of Spice Supplementation in Rheumatoid Arthritis: A Systematic Literature Review

International audienceBackground: Spices, i.e., curcumin, ginger, saffron, and cinnamon, have a thousand-year history of medicinal use in Asia. Modern medicine has begun to explore their therapeutic properties during the last few decades. We aimed to perform a systematic literature review (SLR) of randomized controlled trials (RCTs) assessing the effect of spice supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis, or psoriatic arthritis).Methods: An SLR of RCTs, reviews, and meta-analyses was performed, searching for articles in MEDLINE/PubMed. Abstracts from international rheumatology and nutrition congresses (2017-2020) were also scrutinized. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration's tool and the Jadad scale.Results: Altogether, six studies, assessing the use of spice supplementation only in RA patients, were included: one on garlic supplementation, two on curcumin, one on ginger, one on cinnamon, and one on saffron supplementation. Garlic, ginger, cinnamon, or saffron supplementation was associated with a decrease in RA clinical activity. However, several points limit the external validity of these studies. No conclusion on the impact of curcumin supplementation on RA activity could be drawn due to low-quality studies.Conclusions: Garlic, ginger, cinnamon, and saffron supplementation could have a beneficial effect on RA activity, but the risk of bias of these studies is difficult to assess and data are too limited to recommend them in daily practice

Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

International audienceBackground: We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of probiotics supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis (SpA), or psoriatic arthritis). Methods: A systematic literature review and meta-analysis from RA and SpA randomized controlled trials were conducted searching for articles in MEDLINE/PubMed and abstracts from recent international rheumatology meetings. The control group was a placebo or another dietary intervention. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration tool and the Jadad scale. Results: The initial search yielded 173 articles. Of these, 13 studies were included in the qualitative synthesis, 8 concerning a total of 344 RA patients and 2 concerning a total of 197 SpA patients. Three meta-analyses were also analyzed. Probiotic strains and quantities used were different among trials (5 studies using Lactobacillus sp., 1 trial Bacillus coagulans and the others a mix of different probiotic strains). Time to assess response ranged from 8 weeks to one year. Two studies associated probiotic supplementation with a dietary intervention. Meta-analysis showed a statistically significant decrease of C-reactive protein (CRP) concentration (mean difference (MD)) −3.04 (95% CI −4.47, −1.62) mg/L, p < 0.001; I2 = 20%, n patients = 209) with probiotics in RA. However, after excluding high-risk-of-bias trials of meta-analysis, there was no difference between probiotics and placebo on DAS28 (standard MD −0.54; 95% CI −1.94 to 0.85, p = 0.45, I2 93%, n patients = 143). The two studies on SpA patients showed no efficacy of probiotics. Conclusions: Probiotic supplementation might decrease RA activity with a moderate decrease effect on CRP, but lack of evidence and studies’ heterogeneity do not allow us to propose them to patients with inflammatory arthritis to control their disease. Further RCTs are required in the future to determinate the efficacy of probiotics and the optimal administration design

Impact of type and dose of oral polyunsaturated fatty acid supplementation on disease activity in inflammatory rheumatic diseases: a systematic literature review and meta-analysis

International audienceAbstract Background Polyunsaturated fatty acid (PUFA) supplementation has been reported to improve disease activity in inflammatory rheumatic diseases (IRDs). However, data are often conflicting and studies insufficiently large to draw conclusions. This systematic literature review and meta-analysis aimed to better estimate the effect of oral supplementation with omega (n)-3 and n-6 PUFA on IRD activity in terms of duration, dose, type, and source.Methods The literature was searched in PubMed, EMBASE, and Cochrane Library databases up to October 2020. Studies were reviewed in accordance with PRISMA guidelines. The effect of PUFA supplementation on disease activity was expressed as the standardized mean difference (95% CI). Metaregression and subgroup analyses involved type of IRD, Jadad score, PUFA source (animal or vegetable), and doses.Results We obtained 42 references; 30 randomized controlled studies were included comparing the effects of PUFA versus control on disease activity (710 IRD patients receiving PUFA supplementation and 710 controls, most with rheumatoid arthritis). We found a significant improvement in pain, swollen and tender joint count, Disease Activity Score in 28 joints, and Health Assessment Questionnaire score in IRD patients receiving PUFA supplementation as compared with controls, with a significant decrease in erythrocyte sedimentation rate but not C-reactive protein level. Although meta-regression revealed no difference by IRD type or source or dose of PUFA supplementation, subgroup analysis revealed more parameters significantly improved with animal- than vegetable-derived PUFAs and 3- to 6-month supplementation. Most studies examined high-dose supplementation (>2 g/day).Conclusion PUFA consumption, especially omega-3 from animal source >2 g/day, may improve IRD activity and might be an adjuvant therapy in rheumatoid arthritis.Trial registration The protocol was registered at PROSPERO ( CRD42021253685 )

Efficacy of Oral Vitamin Supplementation in Inflammatory Rheumatic Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

International audienceBackground: We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of oral vitamin supplementation on symptoms and disease activity in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA).Methods: A systematic literature review and meta-analysis of randomized controlled trials including patients with inflammatory rheumatic diseases were performed using MEDLINE, EMBASE and abstracts from recent international rheumatology congresses. Studies were reviewed in accordance with PRISMA guidelines. We analysed clinical outcomes according to each type of vitamin supplementation.Results: The initial search yielded 606 articles. Of these, 13 studies were included in the qualitative synthesis: eight studied vitamin D supplementation, two assessed vitamin E supplementation, two folic acid, and one vitamin K, all of them on RA patients. No studies on SpA or PsA were selected. Oral vitamin supplementations were not associated with a reduction in RA activity (DAS-28 or pain) or RA flares.Conclusions: Despite their beneficial effects, the effects of vitamin supplementation on RA activity, if any, seem to be limited. Evidence on their efficacy on SpA or PsA activity is lacking. However, folic acid supplementation should be suggested to prevent methotrexate-related side effects, and vitamin D should be given to patients with vitamin D deficiency to prevent musculo-skeletal complications

Characteristics of Patients Treated with JAK Inhibitors in Rheumatoid Arthritis before versus after VTE Risk Warnings

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

Actual Persistence of Abatacept in Rheumatoid Arthritis: Results of the French-Ric Network

International audienceObjectives: Data on abatacept (ABA) persistence in routine practice are limited. We aimed to study ABA persistence rates at 12 months, according to the date of initiation, and to analyze the factors associated with persistence at 12 months. Methods: We performed an observational, ambispective, multi-center study from January 2008 to July 2016, based on the French-RIC Network. We defined three groups of patients followed up for rheumatoid arthritis (RA), according to the date of initiation of ABA therapy: Group 1 (from 2007 to 31 July 2010: ABA indicated after anti-TNF failure); Group 2 (from 1 August 2010 to 31 March 2014: ABA indicated after conventional antirheumatic drugs failure); Group 3 (from 1 April 2014 to 1 July 2016: ABA available by the subcutaneous injection). Results: Among 517 patients who initiated ABA, drug persistence at 12 months was 68%. The only factor significantly associated with persistence rate at 12 months was C-reactive protein (CRP) < 10 mg/L at ABA initiation (odds ratio (OR) 0.6, 95% confidence interval 0.3-0.9; p = 0.0016). There was no significant difference in drug persistence according to date of initiation, the line of biological disease-modifying antirheumatic drugs (bDMARD) therapy or the route of administration. Conclusions: In routine practice, over time, ABA has come to be initiated earlier in the course of therapy for RA in France. Abatacept persistence is similar to that reported in the Orencia Rheumatoid Arthritis (ORA) registry, and does not differ according to the date of initiation. The only factor found to be associated with the persistence rate at 12 months was CRP < 10 mg /L at ABA initiation