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Spondyloarthropathies (SpA) are common systemic inflammatory rheumatic diseases, in which, as in other rheumatic diseases, levels of markers of bone resorption are elevated, leading to bone loss and elevated risk of vertebral fractures. However, the diseases are also associated with new bone formation in the spine, the so-called syndesmophytes. We tried to unravel the pathogenesis of formation and growth of syndesmophytes and evaluated new diagnostic and treatment options. After a successful meeting of the Working Group on Rheumatic Diseases at the ECTS 2020, we (WL and CR) were excited about the quality of the speakers (CM, JH, AG, and GL) and their complimentary lectures. Given the relative lack of reviews on spondyloarthropathies and bone, we decided to work together on a comprehensive review that might be interesting for basic scientists and clinically relevant for clinicians. Radiographic progression in axSpA is linked to several risk factors, like male sex, smoking, HLA-B-27, increased levels of CRP, presence of syndesmophytes, and marked inflammation on MRI. The potential role of mechanical stress in the context of physically demanding jobs has been also suggested to promote structural damages. Different treatment options from NSAIDs to biologic agents like TNF inhibitors (TNFi) or IL-17inhibitors (IL-17i) result in a reduction of inflammation and symptoms. However, all these different treatment options failed to show clear and reproducible results on inhibition on syndesmophyte formation. The majority of data are available on TNFi, and some studies suggested an effect in subgroups of patients with ankylosing spondylitis. Less information is available on NSAIDs and IL-17i. Since IL-17i have been introduced quite recently, more studies are expected. IL-17 inhibitors (Il-17i) potently reduce signs and symptoms, but serum level of IL-17 is not elevated, therefore, IL-17 probably has mainly a local effect. The failure of anti-IL-23 in axSpA suggests that IL-17A production could be independent from IL-23. It may be upregulated by TNFα, resulting in lower expression of DKK1 and RANKL and an increase in osteogenesis. In active AS markers of bone resorption are increased, while bone formation markers can be increased or decreased. Bone Turnover markers and additional markers related to Wnt such as DKK1, sclerostin, and RANKL are valuable for elucidating bone metabolism on a group level and they are not (yet) able to predict individual patient outcomes. The gold standard for detection of structural lesions in clinical practice is the use of conventional radiographics. However, the resolution is low compared to the change over time and the interval for detecting changes are 2 years or more. Modern techniques offer substantial advantages such as the early detection of bone marrow edema with MRI, the fivefold increased detection rate of new or growing syndesmophytes with low-dose CT, and the decrease in 18F-fluoride uptake during treatment with TNFα-inhibitors (TNFi) in a pilot study in 12 AS patients. Detection of bone involvement by new techniques, such as low-dose CT, MRI and 18-Fluoride PET-scans, and bone turnover markers, in combination with focusing on high-risk groups such as patients with early disease, elevated CRP, syndesmophytes at baseline, male patients and patients with HLA-B27 + are promising options for the near future. However, for optimal prevention of formation of syndesmophytes we need more detailed insight in the pathogenesis of bone formation in axSpA and probably more targeted therapies.

The importance of interleukin-17A (IL-17A) in the pathogenesis of axial spondyloarthritis (SpA) has been demonstrated by the success of IL-17A blockade. However, the nature of the cell populations that produce this important proinflammatory cytokine remains poorly defined. We undertook this study to characterize the major IL-17A-producing blood cell populations in the peripheral blood of patients with axial SpA, with a focus on mucosal-associated invariant T (MAIT) cells, a population known to be capable of producing IL-17.We evaluated IL-17A production from 5 sorted peripheral blood cell populations, namely, MAIT cells, γδ T cells, CD4+ T cells, CD8+ T cells, and neutrophils, before and after stimulation with phorbol myristate acetate, the calcium ionophore A23187, and β-1,3-glucan. Expression of IL-17A transcripts and protein were determined using nCounter and ultra-sensitive Simoa technology, respectively. MAIT cells from the axial entheses of non-axial SpA control patients (n = 5) were further characterized using flow cytometric immunophenotyping and quantitative polymerase chain reaction, and the production of IL-17 was assessed following stimulation.On a per-cell basis, MAIT cells from peripheral blood produced the most IL-17A compared to CD4+ T cells (P 0.01), CD8+ T cells (P 0.0001), and γδ T cells (P 0.0001). IL-17A was not produced by neutrophils. Gene expression analysis also revealed significantly higher expression of IL17A and IL23R in MAIT cells. Stimulation of peripheral blood MAIT cells with anti-CD3/CD28 and IL-7 and/or IL-18 induced strong expression of IL17F. MAIT cells were present in the normal, unaffected entheses of control patients who did not have axial SpA and showed elevated AHR, JAK1, STAT4, and TGFB1 transcript expression with inducible IL-17A protein. IL-18 protein expression was evident in spinal enthesis digests.Both peripheral blood MAIT cells and resident MAIT cells in normal axial entheses contribute to the production of IL-17 and may play important roles in the pathogenesis of axial SpA.

The coronavirus disease 2019 (COVID-19) pandemic has accelerated changes to rheumatology daily clinical practice. The main goal of the 12th International Immunology Summit, held 25-26 June, 2021 (virtual meeting), was to provide direction for these active changes rather than undergoing change reactively in order to improve patient outcomes. This review describes and explores the concept of change in rheumatology clinical practice based on presentations from the Immunology Summit. Many of the changes to rheumatology practice brought about by the COVID-19 pandemic may be considered as having a positive impact on disease management and may help with the long-term development of more patient-focused treatment. Rheumatologists can contribute key knowledge regarding the use of immunosuppressive agents in the context of the pandemic, and according to the European League Against Rheumatism, they should be involved in any multidisciplinary COVID-19 guideline committees. New technologies, including telemedicine and artificial intelligence, represent an opportunity for physicians to individualise patient treatment and improve disease management. Despite major advances in the treatment of rheumatic diseases, the efficacy of available disease-modifying anti-rheumatic drugs (DMARDs) remains suboptimal and data regarding serological biomarkers are limited. Synovial tissue biomarkers, such as CD68The global COVID-19 pandemic has brought about several changes to the management of patients with rheumatic diseases, such as rheumatoid arthritis, psoriatic arthritis or spondyloarthritis. Many of these changes are considered to have had a positive impact on rheumatology practice, including the potential use of virtual meetings rather than face-to-face consultations. Physicians are increasingly using new technologies to provide patients with individualised treatment. There is a need for more effective treatment options and strategies in patients with rheumatic diseases as well as ways of testing for biomarkers that may predict response to treatment. An improved understanding of the mechanisms underlying disease development may help rheumatologists to develop a new ‘treat-to-target’ approach that addresses the symptoms of the disease as well as their patients’ preferences and quality of life. This may enable rheumatologists to improve their practice methods, thereby reducing diagnostic delays and optimising long-term outcomes in patients with rheumatic diseases.

Resume Objectifs Les inhibiteurs de l’interleukine (IL)-1β, efficaces dans les crises de goutte, sont recommandes en cas de contre-indications a la prise en charge standard, notamment insuffisance renale chronique (IRC) de stade 4 ou 5. Or, il existe peu de donnees disponibles sur l’efficacite et la securite de ces agents dans cette population de patients. Nous avons souhaite explorer l’efficacite et la securite de l’anakinra utilise pour traiter les crises de goutte chez des patients presentant une IRC de stade 4 ou 5 ou ayant subi une transplantation renale. Methodes Cette etude retrospective menee dans trois centres universitaires a inclus des patients consecutifs presentant une IRC de stade 4 ou 5 ou ayant subi une transplantation renale qui prenaient de l’anakinra en traitement d’une arthrite goutteuse aigue et avaient effectue au moins une visite de suivi. L’efficacite, la survenue d’infections et les variations de la fonction renale ont ete consignees. Resultats Sur les 31 patients inclus (24 hommes, âge moyen 72 ± 11 ans), 25 n’avaient pas subi de transplantation et presentaient une IRC de stade 4 ou 5 (estimation du debit de filtration glomerulaire moyen [eDFG] selon la formule MDRD 22,7 ± 6,5 mL/min/1,73 m2) et 6 avaient subi une transplantation renale (eDFG moyen 41,5 ± 22,8 mL/min/1,73 m2). La duree mediane de la goutte etait de 3,5 ans et le taux moyen d’uricemie de 8,7 mg/dL. Vingt-et-un patients (68 %) presentaient des tophi et 21, une arthropathie goutteuse. L’anakinra a ete efficace chez tous les patients (EVA final 10 et CRP finale 10 mg/L). Dix patients (32 %) etaient dependants de l’anakinra (c.-a-d. qu’un traitement prolonge d’anakinra etait necessaire). Une infection grave a ete enregistree chez une seule patiente, trois mois apres l’instauration de l’anakinra. Aucune variation significative de la fonction renale n’a ete observee. Conclusion L’anakinra peut constituer une option therapeutique sure chez les patients goutteux presentant une IRC a un stade avance. Des etudes comparatives randomisees supplementaires sont necessaires pour confirmer nos resultats.

Objectives Interleukin (IL)-1β blocking is effective for the treatment of gout flares and is recommended in patients with contraindications to the standard of care, such as stage 4–5 chronic kidney disease (CKD) patients. However, efficacy and safety data regarding these agents are lacking in this population. We aimed to investigate the efficacy and safety of anakinra for the treatment of gout flares in patients with stage 4–5 CKD or renal transplantation. Methods This retrospective study encompassing 3 academic centres included consecutive patients with stage 4–5 CKD or kidney transplantation who received anakinra for the treatment of acute gouty arthritis and completed at least one follow-up visit. Efficacy, occurrence of infection, and renal function variations were recorded. Results Of the 31 included patients (24 men, mean age 72 ± 11 years), 25 were non-transplant subjects with stage 4–5 CKD (mean estimated glomerular filtration rate, MDRD formula (eGFR) 22.7 ± 6.5 mL/min/1.73 m 2 ), and six had undergone kidney transplantation (mean eGFR 41.5 ± 22.8 mL/min/1.73 m 2 ). Median gout duration was 3.5 years, and the mean serum urate (SUA) level was 8.7 mg/dL. Twenty-one (68%) patients had tophi, and 21 had gout arthropathy. Anakinra was efficacious in all patients (final VAS 10 and CRP level 10 mg/L). Ten patients (32%) were anakinra dependent (i.e., required prolonged treatment with anakinra). A serious infection was recorded in only one patient, occurring 3 months after starting anakinra. No significant variation in renal function was observed. Conclusion Anakinra may be a safe therapeutic option for gout patients with advanced CKD. Further randomized controlled studies are required to confirm our results.

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.

International audience; No abstract available