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Objectives Excessive and inappropriate production of pro-inflammatory cytokines plays a key role in Still’s disease. Janus kinase inhibitor (JAKi) agents mainly block pro-inflammatory cytokine pathways, notably IL-6 and IFN. The objective was to assess the efficacy and safety of JAKi agents in difficult-to-treat systemic JIA or adult-onset Still’s disease (AOSD). Methods This retrospective study was based on a national survey conducted in the departments of rheumatology, paediatric rheumatology and internal medicine of French hospitals regarding systemic JIA and AOSD patients who received JAKi agents. The data were collected with a standardized questionnaire and analysed at different times (treatment initiation, months 1, 3 and 6 and the end of follow-up). Results Nine patients (seven adults) were included. All patients showed inadequate response to CS or conventional synthetic or biologic DMARDs. Baricitinib was used in five patients, ruxolitinib in two, tofacitinib in two and upadacitinib in one. A JAKi was used combined with CS in all but two patients. A JAKi was associated with anakinra and CS in one patient, and with MTX, anakinra and CS in another. The median (range) follow-up was 16 (1–33) months. Two cases out of nine showed complete remission, 3/9 partial response and 4/9 treatment failure. At the last visit, CS could be decreased but not stopped. Tolerance of the JAKi was acceptable (no severe adverse events). Conclusion JAKi agents may be a therapeutic option for some patients with difficult-to-treat Still’s disease, especially those with partial response to medium- or high-dose CS or biologics.

Resume La fatigue est un probleme notable dans le rhumatisme psoriasique. L’objectif de cette revue systematique de la litterature avec meta-analyse etait d’evaluer l’effet des traitements de fond antirhumatismaux biologiques et de l’apremilast sur la fatigue dans des essais comparatifs randomises sur le rhumatisme psoriasique et de comparer cet effet a celui constate sur la douleur dans ces memes essais. Une revue systematique de la litterature a ete realisee dans les bases de donnees PubMed, Embase et Cochrane jusqu’en janvier 2017. Tous les essais comparatifs randomises portant sur les traitements de fond biologiques et l’apremilast dans le rhumatisme psoriasique et evaluant la fatigue (quel que soit le score utilise) ont ete inclus. Deux evaluateurs ont collecte les donnees relatives aux niveaux de fatigue et de douleur, a l’inclusion et au point d’evaluation le plus proche de 24 semaines apres le debut du traitement. Les differences moyennes standardisees compilees ont ete calculees par le logiciel RevMan. Apres selection de 295 publications, sept essais comparatifs randomises ont ete analyses, comparant l’adalimumab (n = 2), le certolizumab pegol (n = 1), le secukinumab (n = 2), l’ustekinumab (n = 1) et l’apremilast (n = 1) a un placebo. Les etudes incluaient 2341 patients avec les caracteristiques (moyenne ponderee ± ecart-type) suivantes : âge 48,6 ± 1,3 ans, duree de la maladie 7,7 ± 1,6 ans, 51,6 % de femmes. La fatigue etait importante a l’inclusion (score d’evaluation fonctionnelle des traitements de maladie chronique (FACIT) : 28,7 ± 2,4). La difference moyenne standardisee compilee etait pour la fatigue − 0,44 (intervalle de confiance a 95 % : − 0,54, − 0,35) et pour la douleur − 0,62 (− 0,73, − 0,52). A 24 semaines, les traitements de fond biologiques et l’apremilast ont eu un effet leger sur la fatigue et plus marque sur la douleur dans les essais comparatifs randomises sur le rhumatisme psoriasique. Il est important de tenir compte de ces resultats dans la prise de decision therapeutique conjointe.

Objectives Systemic-onset JIA (SJIA) and adult-onset Still’s disease (AOSD) are the same sporadic systemic auto-inflammatory disease. SpA is a group of inflammatory non-autoimmune disorders. We report the observations of eight patients with SJIA/AOSD who also presented features of SpA during their disease evolution and estimate the prevalence of SpA in SJIA/AOSD. Methods This was a retrospective national survey of departments of paediatric and adult rheumatology and internal medicine. To be included, SJIA patients had to fulfil the ILAR criteria, AOSD patients the Yamaguchi or Fautrel criteria, and all patients the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial or peripheral SpA, ESSG criteria for SpA or Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA. The data were collected with a standardized form. Results Eight patients (five adults) were identified in one paediatric and two adult departments. In all but one patient, SpA manifestations occurred several years after SJIA/AOSD onset [mean (s.d.) delay 6.2 (3.8) years]. Two patients had peripheral and three axial SpA, and four later exhibited PsA and one SAPHO syndrome. The prevalence of SpA in an adult cohort of 76 patients with AOSD was 6.58% (95% CI 2.17, 14.69), greater than the prevalence of SpA in the French general population (0.3%; 95% CI 0.17, 0.46). The prevalence of SpA in an SJIA cohort of 30 patients was 10% (95% CI 2.11, 26.53), more than that reported in the general population of industrialized countries, estimated at 0.016–0.15%. Conclusion While the temporal disassociation between SpA and AOSD in most cases might suggest a coincidental finding, our work raises the possibility of an SpA/AOSD spectrum overlap that needs further study.

BackgroundBarriers and facilitators to physical activity in inflammatory arthritis can be assessed through the Inflammatory arthritis Facilitators and barriers questionnaire (IFAB) questionnaire. The objective was to measure the correlation between IFAB and self-reported physical activity levels.MethodsThis was an international, multicentric, cross-sectional study in 2019-20 (NCT04426747). Consecutive spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients completed the 10-item IFAB, ranging − 70 to 70 with lower scores indicating more barriers. Physical activity was measured by the IPAQ-S questionnaire, steps per day collected by smartphone, and psychological readiness to change by stages of behavior change. Spearman correlations and multivariable linear regression were calculated.ResultsOf 245 patients included, 150 were analysed: 69 (46%) axSpA, 63 (42%) RA, 18 (12%) PsA. Mean age was 48.6 years (standard deviation, SD 17.1), mean disease duration 11.7 (10.1) years and 60% were women. Barriers to physical activity were moderate: mean IFAB, 6 (SD 19.2); 39 (26%) patients scored less than − 5, corresponding to significant barriers. The mean physical activity was 2837 (SD 2668, median 1784) MET-minutes per week. Physical activity was correlated with the IFAB (rho 0.28, p

Background Barriers and facilitators to physical activity in inflammatory arthritis can be assessed through the Inflammatory arthritis FAcilitators and Barriers (IFAB) questionnaire. The objective was to measure the correlation between IFAB and self-reported physical activity levels. Methods This was an international, multicentric, cross-sectional study in 2019–20. Consecutive spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients completed the 10-item IFAB, which ranges from − 70 to 70 with lower scores indicating more barriers. Physical activity was measured by the IPAQ-S questionnaire, steps per day collected by smartphone, and psychological readiness to change by stages of behaviour change. Spearman correlations and multivariable linear regression were calculated. Results Of 245 patients included, 150 were analysed: 69 (46%) axSpA, 63 (42%) RA, 18 (12%) PsA. Mean age was 48.6 years (standard deviation, SD 17.1), mean disease duration 11.7 (10.1) years and 60% were women. Barriers to physical activity were moderate: mean IFAB, 6 (SD 19.2); 39 (26%) patients scored less than − 5, corresponding to significant barriers. The mean physical activity was 2837 (SD 2668, median 1784) MET-minutes per week. The IPAQ-S questionnaire was correlated with the IFAB (rho 0.28, p p Conclusion Perceived barriers and facilitators to physical activity were correlated with physical activity, indicating that targeting patients with high barriers and low facilitators to physical activity could be an effective option to improve physical activity levels. Trial registration ClinicalTrial NCT04426747. Registered 11 June 2020 - Retrospectively registered.

Background Ciprofloxacin is an antibiotic used in osteoarticular infections owing to its very good bone penetration. Very few pharmacokinetic data are available in this population. Objectives To investigate oral ciprofloxacin population pharmacokinetics in adult patients treated for osteoarticular infections and propose guidance for more effective dosing. Methods A retrospective population-pharmacokinetic analysis was performed on 92 consecutive hospitalized patients in the orthopaedic department. Ciprofloxacin plasma samples were obtained on one or two occasions during treatment. Plasma concentration was measured using ultra-performance liquid chromatography system coupled with tandem mass spectrometry. Data analysis was performed using a non-linear mixed-effect approach via Monolix 2019R2. Results A total of 397 plasma samples were obtained with 11.5% and 41.6% of patients being below the therapeutic target for Gram-negative and staphylococcal infections, respectively. Ciprofloxacin pharmacokinetics were best described by a two-compartment model with a first-order absorption. Ciprofloxacin apparent plasma clearances and volumes of distribution were dependent on patients’ fat-free mass according to the allometric rule. Elimination clearance was also positively related to renal function through the modification of diet in renal disease equation (MDRD) and rifampicin co-administration. When patients are co-treated with rifampicin, ciprofloxacin dosage should be increased by 50% to 60%. Conclusions This study showed that free-fat mass was a better size predictor than total body weight for ciprofloxacin clearance and volumes terms. Moreover, both MDRD and rifampicin status were significant predictors of individual ciprofloxacin clearance. Our study suggests that individual adjustment of ciprofloxacin dose in osteoarticular infections with less-susceptible bacteria might be indicated to reach required efficacy targets.

International audience

Adult-onset Still’s disease (AoSD) is a rare but clinically well-known, polygenic, systemic autoinflammatory disease. Owing to its sporadic appearance in all adult age groups with potentially severe inflammatory onset accompanied by a broad spectrum of disease manifestation and complications, AoSD is an unsolved challenge for clinicians with limited therapeutic options. This Review provides a comprehensive insight into the complex and heterogeneous nature of AoSD, describing biomarkers of the disease and its progression and the cytokine signalling pathways that contribute to disease. The efficacy and safety of biologic therapeutic options are also discussed, and guidance for treatment decisions is provided. Improving the approach to AoSD in the future will require much closer cooperation between paediatric and adult rheumatologists to establish common diagnostic strategies, treatment targets and goals., Adult-onset Still’s disease (AoSD) is not easily diagnosed, and treatment options are limited. This Review provides an overview of the disease and its pathogenesis, clinical trial results, therapeutic options and a plan to diagnose and clinically manage these patients., Key points Similar to systemic-onset juvenile idiopathic arthritis, adult-onset Still’s disease (AoSD) is a rare systemic autoinflammatory disease with potentially severe inflammatory onset accompanied by a broad spectrum of disease manifestation and complications.AoSD should be considered in patients with persistent fever, and the diagnosis is based on the combination of clinical and laboratory findings as well as the exclusion of other inflammatory conditions.Central to the pathogenesis of AoSD is the intense activation of innate immune cells and overproduction of several pro-inflammatory cytokines including IL-1, IL-6 and IL-18.Two IL-1 antagonists have been approved for treatment of AoSD, and growing evidence suggests that other biologic agents are therapeutic options, such as anti-IL-6 and anti-IL-18 therapeutics.As a reliable prediction of response and outcome is not possible, therapeutic decisions have to be made on the basis of clinical, biological or imaging characteristics of disease.A close cooperation between paediatric and adult rheumatologists is required to establish common diagnostic strategies, treatment targets and goals.

Resume La maladie de Still de l’adulte (MSA) est un syndrome auto-inflammatoire systemique rare dont le diagnostic est difficile. Dans les formes typiques, la MSA associe chez un patient âge de plus de 16 ans quatre signes cardinaux : une fievre hectique a 39–40 °C, une eruption cutanee evanescente concomitante des pics febriles, des arthralgies ou arthrites, une hyperleucocytose a polynucleaires neutrophiles. A ces signes peuvent s’associer une multitude d’autres symptomes. Aucune manifestation n’est cependant specifique de la maladie. Avant de retenir un diagnostic de MSA, il reste ainsi necessaire d’eliminer d’autres affections infectieuses, malignes ou systemiques, pouvant mimer une MSA. Des criteres de classification peuvent aider le clinicien a evoquer le diagnostic. Cependant, la MSA est une maladie heterogene, et les formes atypiques ne sont pas rares. La MSA peut predominer sur un organe ou donner d’emblee des complications systemiques avec defaillance pluriviscerale, et mettre en jeu le pronostic vital alors meme que le diagnostic n’est pas clairement pose. Leur gravite relegue souvent les signes articulaires au second plan, et contribue ainsi a egarer encore plus le clinicien peu familier avec la MSA. L’objectif de cet article est donc de rappeler brievement les manifestations des formes typiques de la maladie, mais egalement de sensibiliser le rhumatologue aux situations atypiques et trompeuses qui doivent faire evoquer le diagnostic de MSA. Dans cette demarche diagnostique complexe, le contact avec l’un des centres de reference pour les maladies auto-inflammatoires est conseille.

Objectives Fatigue is a significant issue in psoriatic arthritis. The objective was to assess the effect of biological disease modifying antirheumatic drugs and apremilast on fatigue in psoriatic arthritis randomised controlled trials and to compare this effect with the effect in the same trials, on pain, through a systematic literature review and meta-analysis. Methods A systematic literature review was performed up to January 2017 in PubMed, Embase and Cochrane databases. All randomized controlled trials in psoriatic arthritis of biological disease modifying antirheumatic drugs or apremilast, assessing fatigue (whatever the score used), were included. Data were collected by 2 assessors regarding levels of fatigue and pain at baseline and at the time point closest to 24 weeks after the treatment introduction. Pooled standardized mean differences were calculated using RevMan. Results After screening 295 publications, 7 randomised controlled trials were analysed: they pertained to adalimumab ( n = 2), certolizumab pegol ( n = 1), secukinumab ( n = 2), ustekinumab ( n = 1) and apremilast ( n = 1), compared to placebo. The studies included 2341 patients: weighted mean ± standard deviation age: 48.6 ± 1.3 years, disease duration: 7.7 ± 1.6 years, 51.6% were females. Fatigue levels were high at baseline (Functional Assessment of Chronic Illness Therapy score: 28.7 ± 2.4). The pooled standardized mean difference was, for fatigue −0.44 (95% confidence interval: −0.54, −0.35) and for pain, −0.62 (−0.73, −0.52). Conclusions Biological disease modifying antirheumatic drugs and apremilast had a small effect on fatigue at 24 weeks in psoriatic arthritis randomized controlled trials and a higher effect on pain. These results are important to take into account in shared decision-making.

Resume La maladie de Still de l’adulte (MSA) est une affection auto-inflammatoire systemique rare. La pathogenie de cette maladie est complexe et reste largement incomprise, neanmoins de recentes avancees physiopathologiques ont ouvert la voie a de nouvelles approches diagnostiques. En effet, le diagnostic de la MSA reste parfois difficile a etablir en raison notamment de la rarete de cette maladie mais egalement de l’absence de signes cliniques (pics febriles, arthralgies ou arthrites, eruption cutanee) et biologiques (syndrome inflammatoire biologique, hyperleucocytose ≥ 10,000 cellules/mm3 avec neutrophilie ≥ 80 %) specifiques. Aucune de ces manifestations n’etant specifique de la maladie, le diagnostic n’est retenu qu’apres elimination des diagnostics differentiels tels qu’une neoplasie, une maladie infectieuse ou une pathologie inflammatoire. Outre ces difficultes diagnostiques, d’autres problemes se posent. La MSA est tres heterogene en termes de presentation clinique, d’evolution et de severite. C’est pourquoi de nouveaux marqueurs sont necessaires pour evaluer : (i) l’activite de la maladie ; (ii) la severite de la maladie (par l’identification des patients a risque de defaillance multiviscerale et de complications mettant en jeu le pronostic vital, telles que le syndrome d’activation macrophagique) ; (iii) la forme evolutive de la maladie (qui peut etre monocyclique, intermittente ou chronique, accompagnee d’une inflammation systemique ou d’une arthrite chronique erosive) ; (iv) et l’efficacite du traitement. L’identification de nouveaux marqueurs n’est possible qu’a condition d’avoir une meilleure connaissance des mecanismes physiopathologiques impliques dans la maladie. Apres un apercu des donnees physiopathologiques actuelles de la MSA, cet article passe en revue les principaux marqueurs biologiques qui ont ete proposes dans la litterature au cours de ces dernieres annees.

Resume Les mucopolysaccharidoses (MPS) constituent un groupe de maladies de surcharge lysosomale rares, comprenant un grand nombre d’affections polymorphes, chacune liee a une mutation particuliere responsable du deficit d’une des enzymes impliquees dans la degradation des glycosaminoglycanes, aboutissant a leur accumulation tissulaire. La plupart d’entre elles sont diagnostiquees chez l’enfant ou l’adolescent et sont de mauvais pronostic en raison de l’atteinte viscerale, et ne sont par consequent pas vues par le rhumatologue adulte. Il existe cependant des formes moderees lentement progressives, avec une atteinte musculosquelettique au premier plan et une esperance de vie proche de celle de la population generale. Ces formes cliniques attenuees sont plus susceptibles d’etre diagnostiquees a l’âge adulte, apres plusieurs annees, voire plusieurs decennies d’evolution et d’errance diagnostique. En effet, l’expression clinique de ces pathologies mime parfois celle des rhumatismes inflammatoires chroniques, ce qui engendre un retard diagnostic. La reconnaissance et le diagnostic de ces formes attenuees de mucopolysaccharidoses sont difficiles en raison des manifestations cliniques moderees et/ou non-specifiques, telles que des douleurs ou des raideurs articulaires. Il est donc important que les rhumatologues soient sensibilises a reconnaitre ces affections. Le diagnostic precoce est essentiel, puisque des therapeutiques specifiques telles que le traitement par enzymotherapie substitutive sont actuellement disponibles selon le type de MPS et peuvent, lorsqu’instaurees precocement, ralentir la progression des lesions tissulaires qui sont malheureusement irreversibles. Cet article a pour objectif de passer en revue les principales caracteristiques cliniques et radiographiques, les strategies diagnostiques et l’actualisation de la prise en charge, qui doit etre validee de facon multidisciplinaire par les experts d’un centre labellise de reference. Le role du rhumatologue prend ici toute son importance tant pour la surveillance des symptomes que pour la prevention des complications.

International audience; No abstract available

International audience; Adult-onset Still’s disease (AOSD) is a non-familial, polygenic systemic autoinflammatory disorder. It is traditionally characterized by four cardinal manifestations—spiking fever, an evanescent salmon-pink maculopapular rash, arthralgia or arthritis and a white-blood-cell count (WBC) ≥ 10,000/mm3, mainly neutrophilic polymorphonuclear cells (PMNs)—but many other manifestations and complications can be associated, making clinical expression very heterogeneous and diagnosis sometimes difficult. The AOSD course can be diverse and is currently impossible to predict. Several clinical phenotypes have been described, either on the basis of the evolution of symptoms over time (monocyclic, polycyclic and chronic evolution) or according to dominant clinical evolution (systemic and arthritis subtypes). However, these patterns are mainly based on case series and not on robust epidemiological studies. Furthermore, they have mainly been established a long time ago, before the era of the biological treatments. Thus, based on our personal experience and on recent advances in the understanding of disease pathogenesis, it appears interesting to reshuffle AOSD phenotypes, emphasizing the continuum between AOSD profiles and other systemic autoinflammatory disorders, eventually proposing a research agenda.

Background:Pulmonary Arterial Hypertension (PAH) is a rare but potentially fatal complication of Adult-Onset Still’s Disease (AOSD) (1). To date, only isolated observations have been published.Objectives:To establish the largest case series of AOSD patients with PAH, and to describe their clinical profile, evolution and response to treatments.Methods:Cases were retrospectively identified from the French PAH network database and from an online call of the “Club Rhumatismes et Inflammation” (http://www.cri-net.com). To be included, all patients had to fulfil the Yamaguchi or Fautrel’s criteria for AOSD and PAH had to be confirmed by right heart catheterization. The data were collected using a standardized questionnaire.Results:Thirteen patients were identified. All were female, the mean age at PAH diagnosis was 32± 12 years, 2 (15%) patients were Caucasian, 6 (46%) from Sub-Saharan Africa, 1 (8%) from Asia and 4 (31%) from West Indies. Only 2 (15%) patients were smokers. All patients had a systemic onset of AOSD, 12 had a polycyclic and 1 a chronic articular evolution, and the mean delay between AOSD and PAH diagnosis was 2.9 (range 1.7 -5.4) years. At PAH diagnosis, patients were receiving the following treatments: 13 (100%) corticosteroids (median dose 12 mg [interquartile range (IQR) 9-18]), 3 (23%) methotrexate, 8 (61%) interleukin (IL)-1 inhibitors (exposure median duration 6.7 months [IQR 3.6-8.5]), none IL-6 inhibitors, 2 (15%) TNF inhibitors. Six (46%) patients developed PAH during an AOSD flare. PAH was severe at diagnosis: 2 (15%), 7 (54%) and 4 (31%) patients were in NYHA functional class II, III and IV, respectively, with a median 6-minute walk distance of 289 m [IQR 0-448], a mean pulmonary arterial pressure of 41 ± 12 mmHg, a mean pulmonary arterial occlusion pressure of 6 ± 3 mmHg, a mean cardiac output of 3.9 ± 1.2 L/min, a mean cardiac index of 2.5 ± 0.9 L/min/m2 and a median pulmonary vascular resistance of 7 Wood Units [IQR 6-11]. The treatment prescribed after PAH diagnosis is detailed in the table. The median follow-up was 34 months [IQR 7-42]. Five patients (38.5 %) died. Figure 1 shows the overall survival. The haemodynamic response to PAH treatment seemed to be dissociated from the prognosis since several patients have died while their haemodynamic had improved or almost normalised.Conclusion:PAH is a rare but potentially severe complication of AOSD, leading to death in 38.5% of our cases series. AOSD remission should be physicians’ objective, since PAH seems to occur when the underlying disease is not controlled.References:[1]Feist E, Mitrovic S, Fautrel B. Mechanisms, biomarkers and targets for adult-onset Still’s disease. Nat Rev Rheumatol. 2018;1:603-618.Table 1.Therapeutic managementTreatmentn (%)Inotropic therapy5 (38%)HTAP treatment10 (77%)•0Monotherapy3•oInitial oral dual combination therapy3•nDual combination therapy including intravenous (IV) prostacyclin1•uUpfront triple combination therapy including IV prostacyclin3High-dose corticosteroids9 (69%)Interleukin 1 inhibitors initiation2 (15%)Interleukin 6 inhibitors initiation5 (38%)Acknowledgements:The authors want to thank the Club Rhumatismes et Inflammation for the diffusion of the online call.Disclosure of Interests:None declared

Background:Excessive and inappropriate production of pro-inflammatory cytokines such as interleukin (IL)-1, IL-6 or IL-18, is a pathogenic cornerstone in adult and childhood onset Still’s disease. Beyond therapies targeting IL-1 or IL-6, Janus kinases (JAK) inhibitors have been proposed for adult-onset Still’s disease (AOSD) patients refractory to or intolerant of treatment with biologicals. Recently, it has been suggested that JAK inhibitors might be efficient in refractory AOSD patients1.Objectives:To assess the efficacy and safety of JAK inhibitors in the treatment of refractory systemic juvenile idiopathic arthritis (sJIA) or AOSD.Methods:This retrospective study was based on a national survey of the departments of rheumatology, paediatric rheumatology and internal medicine in all French hospitals from an online call of the “Club Rhumatismes et Inflammation” (www.cri-net.com). The data were collected using a standardized questionnaire, and analyzed at different time points (treatment initiation, M1, M3, M6 and end of the follow-up). The response to JAK inhibitors was categorized as: complete remission (resolution of all clinical and biologic signs), partial remission (clinical improvement with persistence of a few symptoms) or failure (lack of clinical or biological improvement).Results:6 patients (5 adults and 1 child) were recruited (Table 1). Mean age at treatment start was 39.6 years for the AOSD patient and 6 years for the sJIA patient, and mean disease duration was 5.3 years. The clinical expression was predominantly systemic in 5 five patients and chronic articular in one. Response to corticosteroids, conventional synthetic or biological Disease Modifying Anti-Rheumatic Drugs had been considered inadequate in all patients. Baricitinib was used in 3 patients, ruxolitinib in 2, and tofacitinib in 1. Steroids were concurrently used in all patients, anakinra in one, methotrexate and anakinra in one. At a mean (SD) follow-up of 9.5 months, partial response was observed in 4 (66.7%) cases (patients with ruxolitinib, tofacitinib or baricitinib) and failure in 2 (33.3%) (patients with baricitinib). No patient achieved complete remission. At the last visit, steroids could be decreased but not stopped in all patients. Patients with partial response had an average decrease of 72,8% (90% for tofacitinib, 70% for baricitinib, 58.5% for ruxolitinib between the start and the follow-up end date) and non-responder patients were yet able to reduce steroids by 60,5% (Table 1). Tolerance of JAK inhibitors was excellent, however patient 4 experienced an episode of infectious pulmonary disease.Conclusion:JAK inhibitors therapy may be helpful for some patients with refractory Still’s disease. However, no complete response was observed in this short series of cases. There might be a difference of response between the molecules, although the number of patients is too low to draw conclusions. Additional information is thus needed to evaluate more precisely the risk-benefit ratio of this treatment, and a possible difference in efficacy among the different groups of JAK inhibitors.References:[1]Hu Q, Wang M, Jia J, et al. Ann Rheum Dis 2020;0:1–3. doi:10.1136/annrheumdis-2019-216Table 1.Characteristics of the AOSD patientNo.SexAge (year)Main symptomsTreatments before JAKi onsetJAK inhibitorsSteroids at onset (mg/day)Concomitant treatmentResponse at last F-USteroids at the end of F-U (mg/day)F-U (months)1F6Fever, polyarthritis, rashAINS, ANAKI, TOCI, CANAKI, ADA, THALI, INFLIXRUXOLITINIB 5mgx2/day30P1232M28Fever, polyarthritis, rashANAKIBARICITINIB 4mg/day800N1013M32Fever, polyarthritis, rashTOCI+MTX, ANAKI+MTX, CANAKI+MTX, ADA, CICLO, IgIVBARICITINIB 4mg/day16MTX 20 mg/week ANAKINRA 100mg/dayP12194F40Fever, polyarthritis, rashMTX, IMUREL, CICLO, ETANERCEPT, ANAKI+MTX, TOCI+MTX, IgIVRUXOLITINIB 15mgx2/day60ANAKI 200mg/dayP3045F48Fever, polyarthritis, rashTOCI, ANAKI, CICLO, CANAKI, IMURELTOFACITINIB 5mgx2/day500P7.596F50Fever, polyarthralgia, rashANAKIBARICITINIB 4mg/day600N401F-U: Follow-upN: No responseP: Partial responseAcknowledgements:I thank all the coauthors, particularly Stéphane Mitrovic and Bruno Fautrel. Also, a special thank to the CRI.Disclosure of Interests:None declared

Background:Physical activity is important for patients with inflammatory arthritis (IA), such as spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA). They are more prone to physical inactivity but derive specific benefits from regular physical activity (1,2). It is not easy to modify physical activity level (3). Barriers and facilitators to physical activity can be assessed through questionnaires (4), however, it is important to demonstrate a link between these explanatory elements and physical activity levels.Objectives:To measure the correlation between barriers and facilitators to physical activity, assessed through a simple questionnaire, and self-reported physical activity levels.Methods:This was an international, multicentric, cross-sectional study performed between October 2019 and June 2020 (ClinicalTrial NCT04426747). Consecutive patients were included if they had definite axSpA, RA or PsA, were aged above 18 and able to walk. Barriers and facilitators to physical activity were measured using the 10-item Inflammatory arthritis Facilitators and barriers questionnaire (IFAB) (5). The IFAB ranges -70 to 70 with lower scores indicating more barriers; scores below -5 correspond to significant barriers. Physical activity was measured by the IPAQ-S questionnaire (6). Exploratory analyses used steps per day collected by smartphone, and psychological readiness to change by stages of behavior change. Statistical analysis used Spearman correlation (rho, pResults:Of 245 patients included, 150 had analysable data (69 (46%) axSpA, 63 (42%) RA, 18 (12%) PsA). Mean age was 48.6 years (SD 17.1), mean disease duration 11.7 (10.1) years and 60% were women. The mean score of barriers and facilitators to physical activity was 6.0 (SD 19.2, median 4) (Figure 1). A total of 39 (26%) patients scored less than -5, which could justify a targeted intervention. The mean physical activity was 2837 (SD 2668, median 1784) Metabolic Equivalent of Task min per week. Physical activity was correlated with score of barriers and facilitators to physical activity in linear regression (rho 0.28, pTable 1for abstract: correlation between IFAB questionnaire, each items and level of physical activity with or without extreme valuesItemCorrelation with IPAQ-S min/met/week, rhoCorrelation with stage of behavior change, rhoCorrelation with mean steps per day, rhoTotal IFAB score0.28 ***0.35 ***0.08Item 10.29 ***0.16 *0.16 *Item 20.060.020.05Item 30.080.16 *0.01Item 40.130.09-0.07Item 5-0.090.100.07Item 60.22 **0.25 ***-0.05Item 70.22 **0.20 **0.12Item 80.16 *0.26 ***0.11Item 90.150.33 ***0.11Item 100.090.17 *0.02Social support questions0.140.27 ***-0.03Psychological and knowledge status questions0.22 **0.16 *0.09*=PConclusion:Perceived barriers and facilitators to physical activity are correlated with physical activity. Targeting patients with high barriers and low facilitators to physical activity could be an effective option to improve physical activity levels.References:[1]O’DWYER T., et al. Rheumatology 2014. Vol. 53, n° 10, pp. 1812-1817.[2]OSTHOFF, A et al. 2018. Vol. 77, n° 9, pp. 1251-1260. DOI 10.1136/annrheumdis-2018-213585.[3]MARLEY, J, et al: BMC Musculoskeletal Disorders. 2017. Vol. 18, pp. 482. DOI 10.1186/s12891-017-1836-2.[4]COSTE, N., et al. 2019. DOI 10.1016/j.rehab.2019.07.009.[5]DAVERGNE, T, et al. Rheumatology International 2020. DOI 10.1007/s00296-020-04692-4.[6]LEE, PH, et al. 2011. Vol. 8, pp. 115. DOI 10.1186/1479-5868-8-115.Figure 1.Distribution of the IFAB score Footnote: Y axis: effectifs, X axis: IFAB score (possibles values from -70 to 70)Acknowledgements:I have no acknowledgements to declare.We thank the following coinvestigators: Sylvie Rozenberg, Beatrice Banneville, Rachida Inaoui, Emmanuelle Dernis, Athan Baillet and Catherine Beauvais, and we thank Hervé Servy for expert CRO adviceDisclosure of Interests:None declared

Objective Plasmacytoid dendritic cells (PDCs) play a central role in pathogenesis of systemic lupus erythematosus (SLE) through their unique ability to produce large amounts of type I interferon (IFN) upon Toll-like receptor 7 (TLR-7) and TLR-9 triggering. PDCs express specific surface regulatory receptors involved in negative regulation of IFNα secretion. These receptors use the γ-chain of high-affinity Fc receptor (FcR) for IgE, FcɛRI. We undertook this study to test our hypothesis that IgE engagement of FcɛRI on PDCs may impact IFNα production in SLE patients. Methods Serum levels of total IgE were measured in healthy volunteers, SLE patients, and patients with IgE-dependent allergic disorders. FcɛRI expression on PDCs from SLE patients was evaluated by flow cytometry. Purified PDCs were incubated with monoclonal IgE for 24 hours, then stimulated for 18 hours with TLR agonists or immune complexes (ICs). IFNα production by PDCs was detected by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. Expression of TLR-7, TLR-9, and IFN regulatory factor 7 (IRF-7) in PDCs was quantified by quantitative real-time PCR. Results We observed significantly higher IgE levels in SLE patients with quiescent disease than in those with active disease. In SLE patients, IgE levels correlated inversely with disease activity. IgE levels were not associated with the presence of antinuclear IgE. Purified PDCs treated for 24 hours with monoclonal IgE up-regulated FcɛRI expression in an IgE dose–dependent manner. IgE-treated PDCs significantly decreased IFNα secretion and down-regulated CCR7 expression upon stimulation with TLR-7 and TLR-9 ligands and ICs from lupus patients. IgE treatment down-regulated expression of TLR-9 and IRF-7. Conclusion Our results support the notion that IgE plays a protective role in SLE pathogenesis through the modulation of inflammatory response by PDCs.

Joint Bone Spine - In Press.Proof corrected by the author Available online since vendredi 31 aout 2018

Introduction: Adult-onset Still’s disease (AOSD) is a rare systemic auto-inflammatory disorder in which management and treatment have considerably progressed over the past decade. Despite wide use of interleukin (IL)-1 or IL-6 inhibitors, serious complications remain possible. Areas covered: A comprehensive literature search in MEDLINE via Pubmed was performed to review AOSD’s severe and sometimes life-threatening complications: reactive hemophagocytic lymphohystiocytosis, coagulation disorders, fulminant hepatitis, cardiac or pulmonary complications and amyloid A amyloidosis. Expert commentary: Early recognition and prompt management is essential to significantly decrease morbi-mortality. The key question is to determine whether the complication is related to the disease itself or related to or favored by (e.g. infection) the ongoing treatment. For all severe AOSD-related complications, high-dose corticosteroids and supportive measures remain the first-line treatment. In case of inadequate response, combination with IL-1 or IL-6 blockers is justified. Cyclosporine A and etoposide remain of interest, especially in case of reactive hemophagocytic lymphohysitocytosis. Plasma exchange may be useful in case of thrombotic microangiopathy. In the near future, new biologic or non-biologic drugs targeting IL-18 or other cytokines or kinases could be of help.

Background Fatigue is an important aspect of disease both in rheumatoid arthritis (RA) and in psoriatic arthritis (PsA) and is of high priority for patients. In RA, a recent Cochrane meta-analysis found a small effect of biologics on fatigue (standardized mean difference, SMD, 0.43; 95% confidence interval, CI: 0.38–0.49).(1) Little is known about this effect in PsA. Objectives To assess the effect of biologics on fatigue in PsA randomised controlled trials (RCTs) and to compare this effect with the effect in the same trials, on pain, through a systematic literature review (SLR) and meta-analysis (MA). Methods SLR up to January 2017 in PubMed, Embase and Cochrane trials database and in recent congress abstracts, using key words related to PsA and biologics. All RCTs in PsA of any biologic therapy, assessing fatigue (whatever the score used), with data available for fatigue were included. Data were collected by 2 regarding levels of fatigue (6 trials used FACIT, 1 VAS) and pain (if available) at baseline and at the timepoint closest to 24 weeks after the biologic introduction. A MA was performed using RevMan and SMDs were calculated for each trial and each study dose, for fatigue and for pain. A SMD 0.8 as important. Results After screening 295 publications, 7 RCTs were included in the meta-analysis and assessed TNF blockers (N=3: adalimumab N=2, certolizumab pegol, N=1), secukinumab (N=2), apremilast (N=1) and ustekinumab (N=1) with or without methotrexate, compared to placebo. The studies included 2340 PsA patients: weighted mean age ± standard deviation (SD), 48.7±1.3 years, disease duration 7.7±1.3 years, 53.3% were females. At baseline, joint disease activity was high (weighted mean swollen joint count: 13.0±3.1, HAQ-DI: 1.2±0.1, PASI: 10.4±3.3). Fatigue levels were high at baseline (weighted mean FACIT score: 29.2±1.5). The pooled SMD for fatigue was 0.44 (95% CI -0.35, 0.54) and it ranged 0.04 to 0.71 across drugs and trials with a small to moderate effect (Graph). In 6 of the same studies, the pooled SMD for pain was 0.62 (95% CI 0.52, 0.73) and ranged 0.46 to 0.84. Conclusions Biologics had a mild to moderate effect on fatigue at 24 weeks in PsA RCTs. No notable differences across drugs were apparent. Effect sizes were higher on pain with a moderate effect. This effect seems similar to effects noted in RA in the Cochrane meta-analysis (1).These results confirm fatigue may be multifactorial in PsA; biologics bring some improvement at the group level but other treatment modalities should be further explored also. References Almeida C, Choy EHS, He wlett S, Kirwan JR, Cramp F, Chalder T, Pollock J, Christensen R. Biologic interventions for fatigue in rheumatoid arthritis. Cochrane Database of Systematic Reviews 2016, Issue 6. Art. No. CD008334. DOI:10.1002/14651858.CD008334.pub2. Disclosure of Interest None declared

Background Recent progress in the understanding of rheumatoid arthritis (RA) pathogenesis leads to growing interest in the concept of pre-RA, a clinical stage in which very early intervention could be more efficacious. Objectives To assess the efficacy of very early therapeutic interventions in pre-RA patients, i.e., with either undifferentiated arthritis, or ACPA-positive arthralgia/arthritis (ie, very early RA, VERA), through a systematic literature review (SLR) and meta-analysis (MA). Methods The SLR was performed following Cochrane guidelines. The search used “undifferentiated arthritis” or “very early rheumatoid arthritis” (VERA) associated with “therapy” or “treatment”, and was limited to randomized controlled trials (RCTs) published in English over the last five years. It was conducted in Pubmed, Embase and Cochrane RCT databases, as well as EULAR and ACR congress abstracts of the last two years. Two independent readers (SH, BH) extracted the following data through a standardized form: study quality, patient status at baseline (either undifferentiated arthritis or VERA), the type of intervention, and disease characteristics over time as well as occurrence of RA. The main outcomes that were analysed for the meta-analysis were RA occurrence at 52 weeks and beyond and the absence of radiographic progression at week 52. The meta-analysis was performed using RevMan with Mantel-Haenszel method. Results The search identified 595 abstracts, of which 9 RCTs were finally selected (including 2 congress abstracts). Eight were related to undifferentiated arthritis; 1 to VERA. The studies included 1156 patients, weighted mean age 45.8+/-15.2 years, mean symptoms duration 16.2+/-12.6 weeks; 66.0+/-17.7% were female. The occurrence of RA at week 52 or more was available in 7 studies (assessing 800 patients). Early therapeutic intervention – either methylprednisolone (80 to 120mg IM), methotrexate, TNF-blocker, abatacept or rituximab -reduced the risk of occurrence of RA with a pooled odds ratio (OR) of 0.72 (95% CI [0.54; 0.96]), p 0.02 (Figure). There was no statistically significant difference between the treatments or placebo, for the absence of radiographic progression (pooled OR 1.36 [0.82;2.27]) The outcome was assessed at Week 52 for all studies, except for Van Dongen 2007 (PROMPT), where it was assessed at Week 120. MethylPDN, methylprednisolone; MTX, methotrexate. Conclusions This meta-analysis demonstrates that early therapeutic intervention significantly reduces the risk of RA onset in pre-RA patients. The benefit /risk balance and feasibility in clinical practice remain to be further assessed. Disclosure of Interest None declared

Background RA and axSpA natural history comprises periods of low disease activity and flares. There is much interest in the concept of flares. Studies have indicated flares may alter patient quality of life, however, there are few data linking flares to quantifiable outcomes. Objectives The objective was to assess longitudinally the association between patient-reported flares and physical activity assessed objectively using an activity tracker. Methods This prospective multi-center observational study (ActConnect) included patients with definite RA (ACR/EULAR criteria) or axSpA (ASAS criteria) owning a smartphone. Physical activity was assessed continuously over 3 months by the number of steps using an activity tracker, and flares were self-assessed weekly using a specific flare question (“has your disease flared up during the last 7 days?”)[1] with a categorical response according to: no flare, 1 to 3 days flare, or >3 days flare. The relationship between flares and physical activity for each week (time point) was assessed by linear mixed models adjusted on rheumatic disease, sex, age, obesity, biologics and employment status. Results 170/178 patients (91 RA and 79 axSpA patients; 1553 time points) were analyzed: mean age 45.5±12.4 years, mean disease duration 10.3±8.7 years; 60 (35.3%) were males and 90 (52.9%) received biologics. Disease was well-controlled (mean DAS28: 2.3±1.2; mean BASDAI: 3.3±2.1). Physical activity was moderate (mean steps/day, 7067±2770). Flares were frequent (25.5% of the questionnaires); most (76.8%) were of short duration. Flares, in particular >3 days flares, were independently associated with less weekly physical activity (p=0.02–0.03), leading to a relative decrease of physical activity of 12–21% and an absolute decrease ranging from 836 to 1462 steps/day (Table 1). Conclusions Flares were frequent in these low-disease patients, though most flares were of short duration. Flares were related to a moderate decrease in physical activity, confirming objectively the functional impact of patient-reported flares. References VP Bykerk et al, RMD Open, 2016; 2:e000225.doi:10.1136/rmdopen-2015–000225. Disclosure of Interest None declared

BACKGROUND Physical activity can be tracked using mobile devices and is recommended in rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) management. The World Health Organization (WHO) recommends at least 150 min per week of moderate to vigorous physical activity (MVPA). OBJECTIVE The objectives of this study were to assess and compare physical activity and its patterns in patients with RA and axSpA using an activity tracker and to assess the feasibility of mobile devices in this population. METHODS This multicentric prospective observational study (ActConnect) included patients who had definite RA or axSpA, and a smartphone. Physical activity was assessed over 3 months using a mobile activity tracker, recording the number of steps per minute. The number of patients reaching the WHO recommendations was calculated. RA and axSpA were compared, using linear mixed models, for number of steps, proportion of morning steps, duration of total activity, and MVPA. Physical activity trajectories were identified using the K-means method, and factors related to the low activity trajectory were explored by logistic regression. Acceptability was assessed by the mean number of days the tracker was worn over the 3 months (ie, adherence), the percentage of wearing time, and by an acceptability questionnaire. RESULTS A total of 157 patients (83 RA and 74 axSpA) were analyzed; 36.3% (57/157) patients were males, and their mean age was 46 (standard deviation [SD] 12) years and mean disease duration was 11 (SD 9) years. RA and axSpA patients had similar physical activity levels of 16 (SD 11) and 15 (SD 12) min per day of MVPA (P=.80), respectively. Only 27.4% (43/157) patients reached the recommendations with a mean MVPA of 106 (SD 77) min per week. The following three trajectories were identified with constant activity: low (54.1% [85/157] of patients), moderate (42.7% [67/157] of patients), and high (3.2% [5/157] of patients) levels of MVPA. A higher body mass index was significantly related to less physical activity (odds ratio 1.12, 95% CI 1.11-1.14). The activity trackers were worn during a mean of 79 (SD 17) days over the 90 days follow-up. Overall, patients considered the use of the tracker very acceptable, with a mean score of 8 out 10. CONCLUSIONS Patients with RA and axSpA performed insufficient physical activity with similar levels in both groups, despite the differences between the 2 diseases. Activity trackers allow longitudinal assessment of physical activity in these patients. The good adherence to this study and the good acceptability of wearing activity trackers confirmed the feasibility of the use of a mobile activity tracker in patients with rheumatic diseases.

Objectives Mitochondrial DNA (mtDNA) contains sequestered damage-associated molecular patterns that might be involved in osteoimmunological pathogenesis of RA. Here, we aimed to investigate the cellular source of mtDNA and its role in RANK ligand (RANKL) expression by RA SF neutrophils. Methods The gene expression signature of SF neutrophils was examined by proteomic quantitative analysis. Levels of mtDNA in circulating and SF neutrophils from RA patients and OA control subjects were assessed by real-time PCR. Purified neutrophils were challenged in vitro with Toll-like receptor agonists as well as mtDNA. RANKL expression by neutrophils was studied by flow cytometry. Results SF neutrophils from RA patients displayed a gene expression signature of oxidative stress. This stress signature was associated with the release of mtDNA in SF as observed by a significant increase of mtDNA in the SF of RA patients compared with OA patients. mtDNA in RA SF was correlated with systemic inflammation as assessed by CRP concentrations. We also showed that mtDNA drives neutrophil RANKL expression to the same extent as Toll-like receptor agonists. Conclusion Our data identify SF neutrophils as a cellular source of mtDNA that leads to a subsequent expression of RANKL. This highlights the important role of neutrophils in RA osteoimmunology.

Plasmacytoid dendritic cells (PDCs) play a central role in pathogenesis of systemic lupus erythematosus (SLE) through their unique ability to produce large amounts of type I interferon (IFN) upon Toll-like receptor 7 (TLR-7) and TLR-9 triggering. PDCs express specific surface regulatory receptors involved in negative regulation of IFNα secretion. These receptors use the γ-chain of high-affinity Fc receptor (FcR) for IgE, FcɛRI. We undertook this study to test our hypothesis that IgE engagement of FcɛRI on PDCs may impact IFNα production in SLE patients.Serum levels of total IgE were measured in healthy volunteers, SLE patients, and patients with IgE-dependent allergic disorders. FcɛRI expression on PDCs from SLE patients was evaluated by flow cytometry. Purified PDCs were incubated with monoclonal IgE for 24 hours, then stimulated for 18 hours with TLR agonists or immune complexes (ICs). IFNα production by PDCs was detected by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. Expression of TLR-7, TLR-9, and IFN regulatory factor 7 (IRF-7) in PDCs was quantified by quantitative real-time PCR.We observed significantly higher IgE levels in SLE patients with quiescent disease than in those with active disease. In SLE patients, IgE levels correlated inversely with disease activity. IgE levels were not associated with the presence of antinuclear IgE. Purified PDCs treated for 24 hours with monoclonal IgE up-regulated FcɛRI expression in an IgE dose-dependent manner. IgE-treated PDCs significantly decreased IFNα secretion and down-regulated CCR7 expression upon stimulation with TLR-7 and TLR-9 ligands and ICs from lupus patients. IgE treatment down-regulated expression of TLR-9 and IRF-7.Our results support the notion that IgE plays a protective role in SLE pathogenesis through the modulation of inflammatory response by PDCs.

Objectif Les bracelets connectes permettent de mesurer notamment l’activite physique et sont susceptibles de constituer une source de donnees en recherche clinique ou epidemiologique. Neanmoins, l’acceptabilite de ces dispositifs reste a discuter : de recentes etudes (cardiovasculaires) en France et aux Etats-Unis fournissent des resultats peu probants avec un taux d’attrition jusqu’a 90 % en quelques semaines. L’objectif de cette etude etait d’evaluer sur trois mois l’adherence au monitoring de l’activite physique par le port – motive par le medecin specialiste habituel – d’un bracelet connecte chez des patients souffrant de rhumatismes inflammatoires chroniques. Methode Cette etude multicentrique longitudinale observationnelle a inclus de janvier a avril 2016 177 patients souffrant d’un rhumatisme inflammatoire et possedant un smartphone recent, suivis par leur medecin rhumatologue. Les patients devaient porter un bracelet connecte (prenant la forme d’une montre) tous les jours pendant trois mois et le synchroniser regulierement avec leur smartphone. L’adherence etait evaluee par le nombre moyen de jours pendant lesquels le bracelet etait porte et les donnees transmises. Les patients adherents (port de la montre ≥ 80 jours/90) etaient compares aux non-adherents par regression logistique pour evaluer les facteurs favorisant l’adherence (sexe, âge, obesite, activite professionnelle, niveau d’etude, type de rhumatisme, duree d’evolution, evaluation globale de la maladie par le patient, biotherapie). L’acceptabilite etait evaluee par un questionnaire mis en place pour cette etude par les auteurs. Resultats Parmi les 177 patients, 64 (36 %) etaient des hommes ; l’âge moyen etait de 45,4 ans (± 12,4) ; la duree moyenne d’evolution de la maladie de 10 ans ; et 96 (54 %) patients etaient traites par un traitement immunosuppresseur (biotherapie). Les patients ont porte le bracelet pendant en moyenne 80 jours (± 15) ; 124 (70 %) patients etaient consideres comme adherents, car ils avaient porte leur bracelet ≥ 80 jours/90. Les patients adherents ont porte leur bracelet 87,9 % du temps. L’adherence au bracelet tendait a etre positivement associee a un âge plus eleve, au sexe feminin, et a une moins bonne evaluation globale de la maladie (maladie plus symptomatique). Seulement 8 (5 %) patients etaient genes par le bracelet du fait de leur rhumatisme, mais 31 (18 %) patients ont eu besoin d’aide pour la premiere synchronisation. L’acceptabilite du bracelet etait notee par le patient en moyenne a 8,5/10 (0 = inacceptable, 10 = tout a fait acceptable). Respectivement, 108 (63 %) et 47 (27 %) patients envisageaient de continuer a porter le bracelet la plupart du temps ou occasionnellement apres la fin de l’etude ; et a l’issue des trois mois 139 patients (78,5 %) portaient effectivement encore le bracelet. En termes de donnees, le dispositif echantillonnant les moments d’activite a la minute, et agregeant ceux sans activite, 3 598 505 points de mesure furent captes. La non-synchronisation reguliere a occasionne des pertes de donnees (memoire du dispositif limitee a quatre jours). Conclusion Cette etude montre la faisabilite de l’utilisation d’un bracelet connecte chez des patients dont le port est motive par leur medecin. Ceci permet d’envisager d’utiliser les donnees relatives a l’activite physique en recherche clinique et epidemiologique.

Background The evolution of rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) is marked by flares, although their frequency is unclear. Flares may impact physical activity. Activity can be assessed objectively using activity trackers. The objective was to assess longitudinally the frequency of flares and the association between flares and objective physical activity. Methods This prospective observational study (ActConnect) included patients with definite clinician-confirmed RA or axSpA, owning a smartphone. During 3 months, physical activity was assessed continuously by number of steps/day, using an activity tracker, and disease flares were self-assessed weekly using a specific flare question and, if relevant, the duration of the flare. The relationship between flares and physical activity for each week (time point) was assessed by linear mixed models. Results In all, 170/178 patients (91 patients with RA and 79 patients with axSpA; 1553 time points) were analysed: mean age was 45.5±12.4 years, mean disease duration was 10.3±8.7 years, 60 (35.3%) were men and 90 (52.9%) received biologics. The disease was well-controlled (mean Disease Activity Score 28: 2.3±1.2; mean Bath Ankylosing Spondylitis Disease Activity Index score: 3.3±2.1). Patients self-reported flares in 28.2%±28.1% of the weekly assessments. Most flares (78.9%±31.4%) lasted ≤3 days. Persistent flares lasting more than 3 days were independently associated with less weekly physical activity (p=0.03), leading to a relative decrease of 12%–21% and an absolute decrease ranging from 836 to 1462 steps/day. Conclusion Flares were frequent but usually of short duration in these stable patients with RA and axSpA. Persistent flares were related to a moderate decrease in physical activity, confirming objectively the functional impact of patient-reported flares.