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International audience; BACKGROUND: Use of a combination of targeted therapies (COMBIO) in patients with refractory/overlapping immune-mediated inflammatory diseases (IMIDs) has increased, but reported data remain scarce. We aimed to assess effectiveness and safety of COMBIO in patients with IMIDs. METHODS: We conducted a French ambispective multicenter cohort study from September 2020 to May 2021, including adults' patients with 1 or 2 IMIDs and treated at least 3-month with COMBIO. RESULTS: Overall, 143 patients were included. The most common IMIDs were Crohn's disease (63.6%), axial spondyloarthritis (37.7%), and ulcerative colitis (14%). Half of patients had only one IMID, of which 60% were Crohn's disease. Mean duration of COMBIO was 274.5±59.3 weeks, and COMBIO persistence at 104 weeks was estimated at 64.1%. The most frequent COMBIOs combined anti-TNF agents with vedolizumab (30%) or ustekinumab (28.7%). Overall, 50% of patients achieved significant and 27% mild-to-moderate improvement in patient-reported outcomes. Extended duration of COMBIO (aOR=1.09; 95% CI: 1.03-1.14; p=0.002) and diagnoses of two IMIDs (aOR=3.46; 95%CI: 1.29-9.26; p=0.013) were associated with significant improvement in patient-reported outcomes. Incidence of serious infection during COMBIO was 4.51 per 100 person-years (95% CI 2.20-8.27) and 5 COMBIOs were discontinued due to adverse events. CONCLUSIONS: COMBIO can be effective and safe in patients with refractory/overlapping IMIDs.

ObjectivesThe objectives of this study were to describe the incidence of major adverse cardiovascular events (MACEs) in French patients newly benefiting from the French Long-term Illness scheme (LTI) for AS and to evaluate the effect of various treatments on the risk of MACE occurrence.MethodsThis national cohort study was based on the French national medico-administrative database SNDS containing data on hospitalization, the LTI, and outpatient care consumption. All French patients newly receiving LTI benefits for AS from 2010 to 2013 were included. The final follow-up date was 31 December 2018. The occurrences of MACEs [stroke and myocardial infarction (MI)] and comorbidities were identified from algorithms previously described in the literature. Competitive risk analysis using propensity score and inverse weighting was performed to calculate cumulative incidence functions and to determine subhazard ratios (SHRs) for the various treatments of interest.ResultsBetween 2010 and 2013, 22 929 patients were included [mean age 43.0 (s.d. 13.9) years, 44.9% mal]. The 8-year cumulative incidences of MACE, stroke, and MI were 1.81% (1.61–2.05), 0.97% (0.83–1.14), and 0.85% (0.71–1.04), respectively. NSAIDs [SHR: 0.39 (0.32–0.50), P ConclusionMACE incidence rates at 8 years are low in patients newly benefiting from LTI for AS. Our results support the hypothesis of a protective role of NSAIDs and anti-TNF in cardiovascular risk in these patients.

Methotrexate is a key component of the treatment of inflammatory rheumatic diseases and the mainstay of therapy in rheumatoid arthritis. Hepatotoxicity has long been a concern for prescribers envisaging long-term treatment with methotrexate for their patients. However, the putative liver toxicity of methotrexate should be evaluated in the context of advances in our knowledge of the pathogenesis and natural history of liver disease, especially non-alcoholic fatty liver disease (NAFLD). Notably, patients with NAFLD are at increased risk for methotrexate hepatotoxicity, and methotrexate can worsen the course of NAFLD. Understanding the mechanisms of acute hepatotoxicity can facilitate the interpretation of elevated concentrations of liver enzymes in this context. Liver fibrosis and the mechanisms of fibrogenesis also need to be considered in relation to chronic exposure to methotrexate. A number of non-invasive tests for liver fibrosis are available for use in patients with rheumatic disease, in addition to liver biopsy, which can be appropriate for particular individuals. On the basis of the available evidence, practical suggestions for pretreatment screening and long-term monitoring of methotrexate therapy can be made for patients who have (or are at risk for) chronic liver disease.

Objectives To describe the current methods usable to assess intestinal permeability in spondyloarthritis (SpA) and rheumatoid arthritis (RA), to analyze the available data on intestinal permeability in SpA and RA patients and the effects of drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) on intestinal permeability. Methods A systematic review was conducted. Medline, Embase, and Cochrane Library databases were searched. Studies published in the last 40 years (January 1980–September 2020) with patients with SpA and/or RA assessing the intestinal permeability were selected. Results A total of 2916 articles were collected, after discarding 1125 duplicate articles, we analyzed the titles and abstracts of 1791 studies. There were 459 articles that met the inclusion criteria and whose text was read. A total of 23 studies were included in the final analysis. Sample sizes ranged from 6 to 206 participants. In patients with spondyloarthritis, a large majority of studies reported an increase in intestinal permeability regardless of the method used. No increase in intestinal permeability was found in RA patients compared to healthy subject in half of the studies. NSAID treatment does not appear to influence intestinal permeability in SpA and seems to increase the intestinal permeability in RA patients as much as in healthy subjects. Conclusion The results of our review suggest the existence of increased intestinal permeability in SpA patients even in the absence of NSAIDs use and regardless of the method assessing the intestinal permeability. Studies in RA patients are more controversial.

International audience

Introduction: Management of inflammatory rheumatic diseases has evolved based on improved treatment strategies and better management of comorbidities, specifically cardiovascular risk. Methotrexate is one of the first-line treatments in the management of inflammatory rheumatic diseases, but its cardiovascular effects are poorly understood. The purpose of this review is to assess the cardiovascular impact of methotrexate in inflammatory rheumatic disease.Areas covered: Current knowledge about the mechanism of action of methotrexate on cardiovascular tissue is presented. A review of the literature in the Medline, Cochrane and Embase databases was performed. Current data about the cardiovascular effects of methotrexate in rheumatoid arthritis, psoriatic arthritis, and psoriasis are presented.Expert opinion: Mechanism of action of methotrexate is based on the antagonism of purines. It reduces systemic inflammation and oxidative stress and improves the major cardiovascular risk factors. Methotrexate improves cardiovascular risk in rheumatoid arthritis, psoriasis and psoriatic arthritis, but the mechanisms involved are partially identified. Data are controversial regarding its effects on endothelial function and atherosclerosis. Conversely, in the general population and in patients with HIV infection, methotrexate does not modify cardiovascular outcomes. Thus, methotrexate only improves cardiovascular risk by reducing systemic inflammation, and should not be used to prevent cardiovascular events.

Resume Objectif Les patients atteints de spondyloarthrite ankylosante (SA) semblent avoir un risque accru d’osteoporose mais ne sont que rarement depistes. L’objectif de cette etude est d’evaluer l’effet de l’ankylose rachidienne sur le coefficient d’attenuation scanographique (CAS) des vertebres lombaires dans la SA. Methodes Cette etude inclut des patients atteints de SA selon les criteres de New-York et qui ont beneficie, a la fois d’un scanner thoraco-abdomino-pelvien et d’un bilan radiographique durant leur suivi. Le modified stoke ankylosing spondylitis spinal score (mSASSS) a ete evalue sur les radiographies, et la presence d’au moins un syndesmophyte (mSASSS ≥ 2) definissait les patients mSASSS+. L’ankylose d’une vertebre lombaire etait definie comme la presence de ponts osseux avec les 2 vertebres adjacentes. Le CAS a ete mesure de L1 a L5, et le seuil fracturaire etait defini par un CAS ≤ 145 unites Hounsfield (UH). Resultats Soixante-treize SA ont ete incluses (âge moyen : 60,3 (±10,7) ans, 65 hommes (89 %)). Soixante patients (82,2 %) etaient mSASSS+ ; 13 patients (17,8 %) presentaient une ankylose d’au moins une vertebre lombaire. Le CAS de chaque vertebre lombaire n’etait pas significativement different entre les groupes mSASSS- et mSASSS+. Le CAS etait plus bas chez les patients ayant au moins un pont osseux que chez ceux sans (p Conclusion La presence de pont osseux et d’une ankylose complete de vertebres lombaires est significativement associee a un surrisque d’un CAS sous le seuil fracturaire, suggerant une degradation de l’os trabeculaire chez les patients atteints de SA avec ankylose rachidienne.

The positive effects of physical activity in both rheumatoid arthritis and ankylosing spondylitis have been proven, but no clear data is yet published regarding psoriatic arthritis (PsA). The aims of this study were (i) to assess the level of physical activity (PA) in these patients and (ii) to review the effects of PA on articular disease, extra articular symptoms, and overall well-being.The research strategy was performed on Pubmed, Cochrane, PEDro databases using the following keywords: "psoriatic arthritis AND physical activity" without restriction. The PRISMA methodology was used to select and analyze articles. We searched for all studies published online and in English before January 2021.A total of 319 studies were retrieved by our search but only 13 could be included. Two reports showed that 17 and 68% of patients reported practicing regularly physical activity. Exercise improved the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), the general symptoms (pain and fatigue), and the quality of life. Muscle strength and some of cardiovascular comorbidities were also improved. While the studies concerning the risk of enthesitis or flare induced by physical activity are conflicting, recent clinical trials did not mention any adverse event. Finally, rehabilitation programs were associated with a reduction mainly of pain and fatigue.Studies show clear beneficial effects of exercise in PsA on disease activity, on well-being, and on comorbidities, and they seem to outweigh the risk of enthesitis induced by mechanical stress. Further investigations are necessary to confirm these results and to precise the modalities of exercise. Key Points • Psoriatic arthritis patients have a sedentary lifestyle • Physical activity has beneficial effects on disease activity, well-being and reduced some cardiovascular risk factor in psoriatic arthritis • Risk of enthesitis and flares is low with exercise in psoriatic arthritis.

Resume Objectif Le manque de specificite des criteres IRM de l’ASAS pour la spondylarthrite axiale non radiographique (SpA ax NR) justifie d’evaluer la capacite discriminante d’autres anomalies IRM au niveau des sacro-iliaques (SI) et du rachis. Methodes Chez des patients hospitalises pour lombalgies inflammatoires, les performances diagnostiques (sensibilite, specificite, rapport de vraisemblance positif (RVP)) des anomalies IRM ont ete calculees en prenant l’avis d’experts rhumatologues comme reference : (i) sacro-iliaques : œdeme (nombre et localisation), œdeme etendu > 1 cm (deep lesion), metaplasie graisseuse (nombre), erosion (nombre et localisation), backfill ; (ii) rachis dorso-lombaire : œdeme (nombre et localisation), metaplasie graisseuse (nombre), atteinte du segment posterieur. Resultats Dans cette cohorte prospective, 40 SpA ax NR et 79 autres diagnostics ont ete diagnostiques. La presence d’au moins 3 signaux inflammatoires sur les sacro-iliaques (RVP : 25,67 [IC95 % : 3,48–48,9]), la presence d’au moins une erosion sacro-iliaque (RVP : 12,80 [3,04–54]), la combinaison d’un signal inflammatoire et d’une erosion sacro-iliaque (RVP : 11,85 [2,79–50]), la combinaison d’une deep lesion et d’une metaplasie graisseuse (RVP : 15,80 [2,05–121,9]) ou d’une erosion (RVP : 11,86 [1,47–95,01]) presentaient les meilleures performances diagnostiques. La combinaison des criteres IRM rachidiens a ceux des sacro-iliaques augmentait significativement les performances diagnostiques pour le diagnostic de SpA ax NR. Conclusion Devant une suspicion de SpA ax NR, l’interpretation de l’IRM doit comprendre outre la presence et le nombre d’œdeme en STIR sa localisation sur les sacro-iliaques, son etendue, la combinaison avec une erosion ou une metaplasie graisseuse des SI et l’atteinte anterieure du rachis dorso-lombaire.

IntroductionDifferentiating ankylosing spondylitis (AS) from osteitis condensans ilii (OCI) remains challenging for clinicians. The aim of this study was to determine whether Subchondral Bone Attenuation Coefficient of the SacroIliac margins (SBAC-SI) is different in AS, OCI and diffuse idiopathic skeletal hyperostosis (DISH).MethodsA monocentric retrospective observational study was performed at the University Hospital of Besançon. Patients included were followed for AS, DISH or OCI and underwent CT scan including sacroiliac joint. Patients with tumour lesion of bone or a history of pelvic radiotherapy were excluded. AS and OCI patients were matched with a control of the same age and sex. SBAC-SI was evaluated by the sum of 24 identical circular regions of interest, 8 per slice (anterior, middle and posterior).ResultsThirty AS and AS controls, 31 DISH, 29 OCI and OCI controls were included. SBAC-SI score was 9727 (±2430) in the OCI group (pConclusionSBAC-SI is significatively different between AS and OCI and could help to distinguish these two diseases.

Introduction Psoriatic arthritis (PsA) is a chronic inflammatory rheumatism characterized for a long time by a high degree of cardiovascular risk. Chronic inflammation is one of the mechanisms that explain this cardiovascular excess of risk through direct and indirect pathways. In recent years, epidemiological data have changed somewhat since the increasing use of bio-drugs that are effective in reducing this inflammation. The purpose of this review is to assess the current state of cardiovascular morbidity and mortality in PsA and thus to assess the cardiovascular risk in case of PsA. Method We conducted a literature review using Pubmed and Medline databases with the following keywords “Psoriatic Arthritis” AND “cardiovascular” including articles from the last three years. Results It appears that in case of PsA, there is an increased prevalence of high blood pressure, diabetes, obesity and dyslipidemia, and therefore of metabolic syndrome. Insulin resistance is closely linked to PsA. On the other hand, the data are more contrasted for active smoking. There is also arterial inflammation specific to PsA. Finally, at the therapeutic level, the impact of NSAIDs remains controversial, while methotrexate and bio-drugs are beneficial at the cardiovascular level. Conclusion PsA is characterized by an increase in cardiovascular morbidity in relation with insulin resistance. Current treatments seem to improve this risk with a decrease in cardiovascular mortality in comparison with patients with plaque psoriasis but this requires confirmation in larger prospective studies.

Resume Le rhumatisme psoriasique est un rhumatisme inflammatoire chronique heterogene dans sa presentation phenotypique. Le rhumatologue dispose d’un arsenal therapeutique riche. Outre les traitements symptomatiques, des traitements de fond dits « conventionnels synthetiques » et des therapies « ciblees » biologiques ou synthetiques sont proposes selon la presentation clinique et la presence de comorbidites. Certaines de ces therapies ciblees, biologiques disposent desormais de biosimilaires. L’objectif therapeutique, qui doit etre partage avec le patient, est en 2020, la remission ou la faible activite.

The management of inflammatory rheumatic diseases has substantially changed in recent years, as has the profile of patients. The advent of biotherapies has been a revolution in rheumatology and the impact of co-morbidities in the management of these patients is now becoming increasingly important. Metabolic syndrome (MetS) is one of the most frequent comorbidities, and hepatic complications of MetS are not uncommon. MetS is responsible for Non-alcoholic fatty liver disease (NAFLD), characterized by excessive hepatic fat accumulation. In extreme cases, progression to cirrhosis is possible. NAFLD ranks among the top three indications for liver transplantation. We review available data on the safety, especially the risk of infections, of TNF inhibitors (TNFi) in case of NAFLD and in case of liver cirrhosis, in patients with rheumatic disease. In cases of NAFLD without severe fibrosis, available data are reassuring and tend to show a beneficial effect of TNFi on hepatic tissue. In case of cirrhosis, data are conflicting. Further large, well-designed studies are needed to explore this specific issue.

INTRODUCTION To evaluate, factors associated with new ultrasonographic lesions of the anterior chest wall in spondyloarthritis (SpA) after a follow up of 5 years. METHODS SpA Patients included in 2013 in a first study were evaluated five years later. Ultrasound B mode and power Doppler examination of the two sternoclavicular joints and the manubrio-sternal joint were performed by the same two examinators at baseline and five years later. The presence of erosion, synovitis, ankylosis, power Doppler signal, joint effusion and joint space narrowing were assessed blind of the first evaluation. RESULTS Among the 131 patients at baseline, 58 patients were evaluated 5 years later. The mean age was 48.2±11.9 years old, with 86% of male and mainly an axial disease (78%). Patient characteristics are comparable to the original cohort. The most frequent lesions were ankylosis of the manubriosternal joint (38%) and erosions of the sternoclavicular joint (29%). 31 patients (53%) developed a new lesion of the ACW. There is a statistically significant association between new lesions of the ACW and higher ASDAS CRP (1,86±1,07 VS 3,0±2,17 P

Resume Le TEP scanner au 18F-fluoro desoxy glucose (18F-FDG-PET-CT) a montre son interet dans le diagnostic de la pseudo polyarthrite rhizomelique (PPR) et permet d’evaluer l’activite metabolique de l’ensemble de l’appareil locomoteur et en particulier des structures musculaires. L’objectif de cette etude etait d’evaluer l’atteinte musculaire a l’aide du 18F-FDG-PET-CT dans les cas de PPR, par rapport a une population non-PPR. Methodes Il s’agit d’une etude retrospective monocentrique de patients atteints de PPR (criteres ACR/EULAR 2012) qui ont eu un examen au 18F-FDG-PET-CT. Un groupe « temoin » compose de sujets sans manifestations rhumatologiques ayant eu un tel examen dans le cadre d’une recherche de neoplasie ou d’un suivi de maladie neoplasique a egalement ete evalue. L’evaluation TEP comprenait 17 sites suggerant une PPR, comme indique precedemment. Les zones d’hypermetabolisme musculaire ont ete classees de la meme facon selon la meme classification semi quantitative. Les sites d’activite musculaire ont ete identifies. Une comparaison des patients atteints de PPR avec et sans lesion musculaire a ete effectuee a l’aide du test exact de Mann–Whitney ou de Fisher. Resultats Deux cent un cas ont ete examines, impliquant 101 PPR (âge moyen de 68,6 ans) et 100 « temoins » (âge moyen de 67,7 ans). Dans l’ensemble, des lesions musculaires par TEP ont ete observees dans 34 cas (34 %) chez les PPR et 10 cas (10 %) chez les temoins (p = 0,004). Les lesions sont bi ou multifocales dans la moitie des cas. Les sites musculaires affectes sont : les muscles spinaux 19, la ceinture scapulaire 14, la ceinture pelvienne 13, la cuisse 6. Une fasciite a ete retrouvee dans 3 cas. Chez les patients atteints de PPR, l’atteinte musculaire TEP n’etait pas associee a l’âge, a la CRP ou au score TEP global de la PPR. Conclusion Les lesions musculaires evaluees par TEP-CT au 18F-fluorodesoxyglucose sont courantes dans la PPR (1/3 des cas), situees aux sites habituels des symptomes de la maladie, sans association avec l’âge, les niveaux de CRP ou le score global de la PPR par TEP. Le muscle doit etre evalue avec soin lors d’un examen TEP dans les cas de PPR.

There is little epidemiological data on global mortality in spondyloarthritis (SpA) and inflammatory bowel disease. We then determined mortality rates of ankylosing spondylitis (AS), psoriatic arthritis (PsA), Crohn's disease (CD) and ulcerative colitis (UC) both globally and by country, and to describe their evolution between 2001 and 2015.We used mortality data from the World Health Organisation (WHO), which shows the number of deaths classified by age, sex, and cause of death coded by ICD-10. Age-standardized mortality rates (ASMR) were constructed using the 2015 WHO reference population. Temporal trend analyses of ASMR were performed between 2001 and 2015 using joinpoint regression.Global ASMR was for 0.13 [0.11-0.14] deaths per million inhabitants for AS, 0.04 [0.03-0.05] for PsA, 0.86 [0.82-0.89] for CD and 0.76 [0.73-0.79] for UC. The worldwide trend analysis showed no significant change in ASMR for AS, a statistically significant increase from 2004 to 2015 (mean annual percent change (APC): 5.94%, p0.001) for PsA, and a statistically significant decrease from 2001 to 2015 for CD (mean APC: -0.82%, p0.001) and UC (mean APC: -1.29%, p0.001). Statistically significant geographical disparities were identified.We found significant geographical disparities in SpA and IBD mortality across the world. Further studies seem to be needed to better understand the evolution of mortality over the last twenty years.