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Introduction Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterised by inflammatory low back pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as a first treatment in axSpA. In case of inadequate response to NSAIDs, biological disease-modifying antirheumatic drugs (bDMARDs) should be introduced according to the recommendations of the European League Against Rheumatism (EULAR) and the American College of Rheumatology. Until 2015, only bDMARD was recommended for axSpA in case of failure to anti-tumour necrosis factor (TNF). The 2022 Assessment of SpondyloArthritis International Society (ASAS)-EULAR recommendation proposed to start an alternative bDMARD but without advocating a switch in mode of action as proposed in rheumatoid arthritis. Since 2015, the inhibition of interleukin (IL)-17 has demonstrated efficacy in axSpA. Then, we designed a randomised multicentre clinical trial to identify the more effective treatment after a first anti-TNF failure in axSpA, comparing an anti-IL-17 to a second anti-TNF.Methods and analysis The ROC-SpA (Rotation Or Change of biotherapy after first anti-TNF treatment failure in axSpA patients) study is a prospective, randomised, multicentre, superiority open-label phase IV trial comparing an anti-IL-17 strategy (secukinumab or ixekizumab) to a second TNF blocker in a 1:1 ratio. Patients with an active axSpA (Bath Ankylosing Spondylitis Disease Activity Index >4 or ankylosing spondylitis disease activity score (ASDAS) >3.5) with inadequate 3 months response to a first anti-TNF and with a stable dose of conventional synthetic DMARDs, oral corticosteroids and/or NSAIDs for at least 1 month are included in 31 hospital centres in France and Monaco. The primary outcome is the ASAS40 response at week 24. The secondary outcomes are ASAS40 at weeks 12 and 52, other clinical scores (ASAS20, partial remission rate, ASDAS major improvement rate) at weeks 12, 24 and 52 with the drugs and anti-drugs concentrations at baseline, weeks 12, 24 and 52. The primary analysis is performed at the end of the study according to the intent-to-treat principle.Ethics and dissemination Ethics approval was obtained from the committee for the protection of persons (Comité de protection des personnes Ouest IV #12/18_1, 6 February 2018) and registered in ClinicalTrials.gov and in EudraCT. Results of this study, whether positive or negative, will be presented at national and international congresses, to national axSpA patient associations and published in a peer-reviewed journal. It could also impact the international recommendation to manage patients with axSpA.Trial registration number NCT03445845 and EudraCT2017-004700-22.

Introduction The therapeutic interest of targeting B-cell activating factor (BAFF) in Sjögren’s disease (SjD) can be suspected from the results of two phase II clinical trials but has not been evaluated in an animal model of the disease. We aimed to evaluate the therapeutic efficacy of this strategy on dryness and salivary gland (SG) infiltrates in the NOD mouse model of SjD.Material and methods Female NOD mice between ages 10 and 18 weeks were treated with a BAFF-blocking monoclonal antibody, Sandy-2 or an isotype control. Dryness was measured by the stimulated salivary flow. Salivary lymphocytic infiltrates were assessed by immunohistochemistry. Blood, SGs, spleen and lymph-node lymphocyte subpopulations were analysed by flow cytometry. SG mRNA expression was analysed by transcriptomic analysis.Results BAFF inhibition significantly decreased SG lymphocytic infiltrates, which was inversely correlated with salivary flow. The treatment markedly decreased B-cell number in SGs, blood, lymph nodes and spleen and increased Foxp3+ regulatory and CD3+CD4−CD8− double negative T-cell numbers in SGs.Conclusion A monoclonal antibody blocking BAFF and depleting B cells had therapeutic effectiveness in the NOD mouse model of SjD. The increase in regulatory T-lymphocyte populations might underlie the efficacy of this treatment.

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Objective The C reactive protein polymyalgia rheumatica activity score (CRP-PMR-AS) is a composite index that includes CRP levels and was developed specifically for PMR. As treatments such as interleukin-6 antagonists can normalise CRP levels, the erythrocyte sedimentation rate (ESR) of PMR-AS, the clinical (clin)-PMR-AS and the imputed-CRP (imp-CRP)-PMR-AS have been developed to avoid such bias. Our primary objective was to measure the correlation of these activity scores. Our secondary objective was to evaluate the concordance between different cutoffs of the PMR-ASs.Method Data from the Safety and Efficacy of tocilizumab versus Placebo in Polymyalgia rHeumatica With glucocORticoid dEpendence (SEMAPHORE) trial, a superiority randomised double-blind placebo-controlled trial, were subjected to post hoc analysis to compare the efficacy of tocilizumab versus placebo in patients with active PMR. The CRP-PMR-AS, ESR-PMR-AS, clin-PMR-AS and imp-CRP-PMR-AS were measured at every visit. The concordance and correlation between these scores were evaluated using kappa correlation coefficients, Bland-Altman correlations, intraclass correlation coefficients (ICCs) and scatter plots.Results A total of 101 patients were included in the SEMAPHORE trial, and 100 were analysed in this study. The correlation between the PMR-ASs was excellent, as the ICC and kappa were >0.85 from week 4 until week 24 (CRP-PMR-AS ≤10 or >10). Bland-Altman plots revealed that the differences between the CRP-PMR-AS and the other threescores were low. The cut-off values for the clin-PMR-AS were similar to those for the CRP-PMR-AS 86% of the time.Conclusion The correlation between all the PMR-ASs was excellent, reflecting the low weight of CRP. In clinical trials using drugs that have an impact on CRP, the derived activity scores can be used.Trial registration number NTC02908217.

Introduction Colchicine, commonly used in gout flare, is contraindicated in severe chronic kidney disease (CKD) (estimated glomerular filtration rate

Objectives Patients with psoriatic arthritis (PsA) are at a significantly increased risk of hyperuricaemia and development of gout, and those with hyperuricaemia have been found to respond poorly to PsA treatment and have more peripheral and destructive joint damage. We present a comprehensive post hoc analysis using pooled data from the FUTURE 2–5 studies and the MAXIMISE study to further evaluate the impact of hyperuricaemia on clinical presentation/disease severity and response to secukinumab in patients with PsA.Methods Patients were stratified into two groups based on baseline serum uric acid (SUA) level (threshold of 360 µmol/L). A sensitivity analysis was also performed based on SUA thresholds of 300 µmol/L and 420 µmol/L. Demographics, clinical, radiological characteristics and comorbidities data were collected.Results At baseline, patients with hyperuricaemia were mostly male, reported a higher prevalence of hypertension, with more clinical dactylitis, more psoriasis and more severe skin disease compared with patients with normouricaemia. A similar proportion of patients in the normouricaemic and hyperuricaemic cohorts achieved American College of Rheumatology responses, resolution of enthesitis and dactylitis, inhibition of structural damage progression and improvement in health-related quality of life across all secukinumab doses at week 52.Conclusion Patients with PsA and hyperuricaemia have different clinical characteristics from patients with PsA and normouricaemia. Identification of these patients at an early stage may facilitate a personalised treatment approach and improved management of comorbidities. Furthermore, secukinumab provided a rapid and sustained response across all manifestations of PsA up to week 52, irrespective of baseline uricaemia status.

Objectives The objective of this systematic review was to provide an overview of current developments and potentially available therapeutic options for spondyloarthritis (SpA) in the coming years.Methods We conducted a systematic review of 17 national and international clinical trial databases for all disease-modifying antirheumatic drugs (DMARDs) for SpA that are already marketed, in clinical development or withdrawn. The search was performed on February 2023 with the keywords “spondyloarthritis”, “ankylosing spondylitis” and “psoriatic arthritis”. For each molecule, we only considered the study at the most advanced stage of clinical development.Results Concerning axial SpA (axSpA), a total of 44 DMARDs were identified: 6 conventional synthetic DMARDs (csDMARDs), 27 biological DMARDs (bDMARDs) and 11 targeted synthetic DMARDs (tsDMARDs). Among the 18 targeted treatments (b+tsDMARDs) in current development, corresponding trials reached phase I (n=1), II (n=10) and III (n=7). Ten molecules are IL-17 inhibitors, two Janus kinase (JAK) inhibitors and two granulocyte-macrophage colony-stimulating factor inhibitors; four have another mode of action. Concerning psoriatic arthritis (PsA), 44 DMARDs were identified: 5 csDMARDs, 27 bDMARDs and 12 tsDMARDs. Among the 15 molecules in current development, corresponding trials reached phase II (n=8) and III (n=7). Six molecules are JAK inhibitors, six IL-17 inhibitors and one an IL-23 inhibitor; two have another mode of action.Conclusion This systematic review identified 18 and 15 molecules in clinical development for axSpA and PsA, respectively, which suggests a strengthening of the therapeutic arsenal in the coming years. However, with so many DMARDs but low target diversity, we will need to develop strategies or biomarkers to help clinicians make informed treatment decisions.

Objective Innate lymphoid cells (ILCs) are a cell population implicated in the pathogenesis of various chronic inflammatory diseases, but little is known about their role in primary Sjögren’s syndrome (pSS). The aim of this study was to assess the frequency of ILC subsets in peripheral blood (PB) and their quantity and location in minor salivary glands (MSGs) in pSS.Methods The frequency of ILC subsets was analysed in the PB of patients with pSS and healthy controls (HCs) by flow cytometry. The amount and location of ILC subsets in MSGs were studied in patients with pSS and sicca controls by immunofluorescence assay.Results In PB, the frequency of ILC subsets did not differ between patients with pSS and HCs. The circulating frequency of the ILC1 subset was increased in patients with pSS with positive anti-SSA antibodies and that of the ILC3 subset was reduced in patients with pSS with glandular swelling. In MSGs, the ILC3 number was higher in lymphocytic-infiltrated than non-infiltrated tissue in patients with pSS and normal glandular tissues in sicca controls. The ILC3 subset was preferentially located at the periphery of infiltrates and was more abundant in small infiltrates of recently diagnosed pSS.Conclusion Altered ILC homeostasis mainly concerns salivary glands in pSS. Most ILCs in MSGs consist of the ILC3 subset, located at the periphery of lymphocytic infiltrates. The ILC3 subset is more abundant in smaller infiltrates and in recently diagnosed pSS. It might play a pathogenic role in the development of T and B lymphocyte infiltrates in the early stages of pSS.

Objective: COVID-19 outcome may be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases (RMD) receiving immunosuppressive therapy. We aimed to investigate whether RMD patients on anti-IL6 therapy prior to SARS-CoV-2 infection have less severe disease and better outcomes of COVID-19. Methods: We conducted a retrospective national, multicentre cohort study using data from the French RMD COVID-19 cohort. We compared the severity and outcome of highly suspected or confirmed COVID-19 infection in RMD patients previously treated with tocilizumab or sarilumab (anti-IL6 group) with patients who did not receive anti-IL6 therapy (no anti-IL6 group). Results: Data were collected for 1883 patients with mean age of 55.2 years [SD 16.7] and 1256 (66.7%) female. Two hundred ten (11.1%) developed severe COVID-19 and 115 (6.4%) died. After adjusting for potential confounding factors, severe COVID-19 was less frequent in the anti-IL6 group compared with the no anti-IL6 group (aOR for moderate vs. mild severity, 0.23 [95% CI, 0.10 to 0.54], p ≤ 0.01 and aOR for severe vs. mild, 0.29 [95% CI, 0.10 to 0.81], p ≤ 0.01). No significant differences were found for the evolution of COVID-19 between the anti-IL6 group and the no anti-IL6 group (aOR for recovery with sequelae vs recovery without sequelae, 0.78 [95% CI, 0.41 to 1.48] and aOR for death vs recovery without sequelae, 0.29 [95% CI, 0.07 to 1.30]). Conclusion: RMD patients receiving anti-IL6 therapy prior to SARS-CoV-2 infection have less severe forms of COVID-19. No difference was observed in COVID-19 evolution, i.e., sequelae or death, between the groups.

Objectives To assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases.Methods The TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019.Results Hundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10).Safety: 11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued.Conclusion These initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.

Abstract Background The risk of severe COVID-19 and its determinants remain largely unknown in patients with autoimmune and inflammatory rheumatic diseases. The objective of this study was to assess the prevalence of COVID-19 infection in patients followed for rare autoimmune diseases as well as the predictors of COVID-19 and disease flare-ups. Methods Cross-sectional phone survey from April 9, 2020, to July 2, 2020, during which patients with autoimmune diseases followed at the National Reference Center for Rare Autoimmune diseases of Strasbourg were systematically contacted by phone and sent a prescription for a SARS-CoV-2 serology. Results One thousand two hundred thirty-two patients were contacted. One thousand fifty-five patients with a confirmed diagnosis of systemic autoimmune disease were included (4 unreachable, 4 moves abroad, 5 deaths before pandemic, 50 without consent, and 114 without autoimmune disease). Among them, 469 (44.5%) patients were tested for SARS-CoV-2 serology. Thirty-nine patients (7.9%) had SARS-CoV-2 infection (either through chest CT-scan [n = 5], RT-PCR on nasopharyngeal swab [n = 14], or serology [n = 31]) among the 496 who underwent at least one of those 3 diagnosis modalities. Of the 39 proven cases, 33 had clinical manifestations (6 asymptomatic patients were diagnosed through systematic serology testing), 31 were managed by home care, 3 were hospitalized due to a need for oxygenation, two required admission to an intensive care unit, and one died. Among patients with confirmed SARS-CoV-2 infection, reported flares were more frequent than in uninfected patients (26.3% [10/38] vs. 7.0% [32/457], p

The management of psoriatic arthritis (PsA) has long been equated with that of rheumatoid arthritis (RA), particularly because methotrexate (MTX) was found efficient in RA in the 1990s. However, results of collective evidence-based medicine, included and argued in this narrative review, do not currently support the use of MTX as first-line therapy in severe PsA. A recent Cochrane systematic review examining the efficacy of MTX in PsA concluded that low-dose MTX was only slightly more effective than placebo. Questions about a structural effect of MTX in PsA remains non-elucidated. Even if tolerance data on MTX are more consensual and adverse events generally non-severe, subjective side effects such as fatigue might lead to MTX withdrawal based on the patient’s decision. PsA patients with axial disease, radiographic lesions, and extensive and disabling skin or joint involvement should receive early treatment with targeted therapy and no longer with MTX. Finally, the usefulness of MTX combined with targeted therapies is limited. MTX does not affect efficacy but only seems to increase the therapeutic maintenance of monoclonal TNF inhibitors. This narrative review may help clarify the place of MTX in PsA management. It allows for reflection on the evolution of current concepts and practices.

The antimalarial hydroxychloroquine (HCQ) has demonstrated several crucial properties for the treatment of systemic lupus erythematosus (SLE). Herein, we reviewed the main HCQ pharmacologic features, detailed its mechanism of action, and summarized the existing guidelines and recommendations for HCQ use in rheumatology with a systematic literature search for the randomized controlled trials focused on lupus. HCQ has been shown to decrease SLE activity, especially in mild and moderate disease, to prevent disease flare and to lower the long-term glucocorticoid need. The numerous benefits of HCQ are extended to pregnancy and breastfeeding period. Based on cohort studies, antithrombotic and metabolic HCQ’s effects were shown, including lipid-lowering properties, which might contribute to an improved cardiovascular risk. Moreover, early HCQ use in antinuclear antibodies positive individuals might delay the progression to SLE. Finally, HCQ has a significant favorable impact on long-term outcomes such as damage accrual and mortality in SLE. Based on these multiple benefits, HCQ is now the mainstay long-term treatment in SLE, recommended by current guidelines in all patients unless contraindications or side effects. The daily dose associated with the best compromise between efficacy and safety is matter of debate. The concern regarding retinal toxicity rather than proper efficacy data is the one that dictated the daily dosage of ⩽5 mg/kg/day actual body weight currently agreed upon.

B and T lymphocyte attenuator (BTLA) is a co-inhibitory receptor that is expressed by lymphoid cells and regulates the immune response. Consistent with an inhibitory role for BTLA, the disease is exacerbated in BTLA-deficient lupus mice. We recently demonstrated that the BTLA pathway is altered in CD4+ T cells from lupus patients. In the present work, we aimed at delineating the expression pattern of BTLA on CD4+ T cell subsets suspected to play a key role in lupus pathogenesis, such as circulating follicular helper T cells (cTFH) and regulatory T cells (Tregs). We did not detect significant ex vivo variations of BTLA expression on total CD4+ T cells (naive and memory), cTFH or TFH subsets between lupus patients and healthy controls. However, we interestingly observed that BTLA expression is significantly increased on activated Tregs, but not resting Tregs, from lupus patients, especially those displaying an active disease. Moreover, it correlates with the diminution of the Tregs frequency observed in these patients. We also showed that both BTLA mRNA and protein expression remain low after TCR stimulation of activated Tregs sorted from healthy donors and evidenced a similar dynamic of BTLA and HVEM expression profile by human Tregs and effector CD4+ T cells upon T cell activation than the one previously described in mice. Finally, we observed that the HVEM/BTLA ratio is significantly lower in Tregs from lupus patients compared to healthy controls, whereas ex vivo effector CD4+ T cells express higher BTLA levels. Our data suggest that an altered expression of BTLA and HVEM could be involved in an impaired regulation of autoreactive T cells in lupus. These results provide a better understanding of the BTLA involvement in lupus pathogenesis and confirm that BTLA should be considered as an interesting target for the development of new therapeutic strategies.

Background: Antimalarial agents (AMs), mainly hydroxychloroquine (HCQ) and chloroquine, are the cornerstone of treatment of cutaneous and systemic lupus erythematosus. However, many aspects of AM prescription remain empirical. The aim of this study was to assess the modalities of AM prescription among physicians treating patients with lupus and to verify the assumption that AM use is heterogeneous and frequently at variance with international guidelines. Methods: We performed an international cross-sectional study among physicians involved in lupus care, using a web-based survey (from September 2019 to July 2020) addressing the main controversial aspects of AM prescription. Results: A total of 298 physicians [median age: 42 (interquartile range: 17) years, mainly internists and rheumatologists] from 35 countries participated to the study. A total of 93% used HCQ as the first-line AM, 69.5% used fixed doses of AMs (mainly 400 mg/day for HCQ) and only 37.9% adjusted the dose in case of renal failure. The main reasons for measuring HCQ blood levels were suspected non-adherence (55.7%) and failure of AM treatment (34.1%). In case of AM failure, 58.0% added an immunosuppressive agent. In case of remission, 49.7% maintained the same dose of AM, whereas 48.3% reduced the dose. One-third of respondents reported not following the American screening guidelines on AM retinal toxicity and 40.9% started retinal screening from the first year of treatment. Conclusion: This study highlights the strong heterogeneity of AM prescription in lupus, as well as several key unmet needs regarding AMs. This may be improved by developing more comprehensive recommendations and favoring dissemination among physicians.

Background: Pathogenic inflammatory pathways are largely shared between different autoimmune and inflammatory diseases (AIDs). This offers the potential to develop a given targeted therapy in several AIDs. Methods: We analyzed two clinical trials registries (ClinicalTrials.gov and EU Clinical Trials Register) to identify the targeted therapies whose development is shared between at least two of the most common AIDs [rheumatoid arthritis (RA), spondyloarthritis (SpA), cutaneous psoriasis (cPso), inflammatory bowel diseases (IBD), systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM), giant cell arteritis (GCA), and multiple sclerosis (MS)] using an in-depth repurposing analysis. Results: We identified 142 shared targeted therapies. The four diseases in which shared targeted therapies were the most numerous were RA ( n = 92), cPso ( n = 67), IBD ( n = 58), and SLE ( n = 56). The two clusters of diseases between which the overlap of targeted therapies was the most important were RA and SLE as well as RA, SpA, cPso, and IBD. The targeted therapies which were shared by five diseases or more were abatacept, ustekinumab, rituximab, anakinra, etanercept, infliximab, secukinumab, tofacitinib, alemtuzumab, tocilizumab, adalimumab, apremilast, baricitinib, belimumab, brodalumab, filgotinib, and upadacitinib. The most frequently targeted molecules and pathways were (by descending frequency): JAK-STAT pathways, Th17 axis, TNF-α, IL-6, costimulation molecules, BAFF, CD20, BTK, chemokines and integrins, IL-1, and type I interferon. Conclusion: Many targeted therapies are developed in several AIDs, reflecting the overlap of pathogenic pathways and potential of drug repurposing. This suggests that a revision of the current, clinically based classification of AIDs towards a more mechanistic-based taxonomy might be relevant.

Aims: With the arrival of conventional synthetic (csDMARDs), biological (bDMARDS) and then targeted synthetic (tsDMARDs) disease-modifying anti-rheumatic drugs, the therapeutic arsenal against rheumatoid arthritis (RA) has recently expanded. However, there are still some unmet needs for patients who do not achieve remission and continue to worsen despite treatments. Of note, most randomized controlled trials show that, for methotrexate-inadequate responders, only 20% of patients are ACR70 responders. With our better understanding of RA pathogenesis, finding new treatments is a necessary challenge. The objective of our study was to analyse the whole pipeline of immunosuppressive and immunomodulating drugs evaluated in RA and describe their mechanisms of action and stage of clinical development. Methods: We conducted a systematic review of all drugs in clinical development in RA, in 17 online registries of clinical trials. Results: The search yielded 4652 trials, from which we identified 243 molecules. Those molecules belong to csDMARDs ( n = 22), bDMARDs ( n = 118), tsDMARDs ( n = 103). Twenty-four molecules are already marketed in RA in at least one country: eight csDMARDs, 10 bDMARDs and six tsDMARDs. Molecules under current development are mainly bDMARDs ( n = 34) and tsDMARDs ( n = 33). Seven of those have reached phase III. A large number of molecules (150/243, 61.7%) have been withdrawn. Conclusion: Despite the availability of 24 marketed molecules, the development of new targeted molecules is ongoing with a total of 243 molecules in RA. With seven molecules currently reaching phase III, we can expect an increase in the armamentarium in the years to come.

Introduction: Few data are available concerning the effect of SARS-CoV-2 vaccination on the persistent symptoms associated with COVID-19, also called long-COVID or post-acute sequelae of COVID-19 (PASC). Patients and methods: We conducted a nationwide online study among adult patients with PASC as defined by symptoms persisting over 4 weeks following a confirmed or probable COVID-19, without any identified alternative diagnosis. Information concerning PASC symptoms, vaccine type and scheme and its effect on PASC symptoms were studied. Results: 620 questionnaires were completed and 567 satisfied the inclusion criteria and were analyzed. The respondents’ median age was 44 (IQR 25–75: 37–50) and 83.4% were women. The initial infection was proven in 365 patients (64%) and 5.1% had been hospitalized to receive oxygen. A total of 396 patients had received at least one injection of SARS-CoV-2 vaccine at the time of the survey, after a median of 357 (198–431) days following the initially-reported SARS-CoV-2 infection. Among the 380 patients who reported persistent symptoms at the time of SARS-CoV-2 vaccination, 201 (52.8%) reported a global effect on symptoms following the injection, corresponding to an improvement in 21.8% and a worsening in 31%. There were no differences based on the type of vaccine used. After a complete vaccination scheme, 93.3% (28/30) of initially seronegative patients reported a positive anti-SARS-CoV-2 IgG. A total of 170 PASC patients had not been vaccinated. The most common reasons for postponing the SARS-CoV-2 vaccine were fear of worsening PASC symptoms (55.9%) and the belief that vaccination was contraindicated because of PASC (15.6%). Conclusion: Our study suggests that SARS-CoV-2 vaccination is well tolerated in the majority of PASC patients and has good immunogenicity. Disseminating these reassuring data might prove crucial to increasing vaccine coverage in patients with PASC.

Avascular osteonecrosis (AVN) is a bone complication that indicates poor functional prognosis. Modern immunosuppressive and steroid-sparing drugs have significantly lowered the occurrence of AVN after kidney transplantation (KT). However, recent data on its incidence rates and risk factors are lacking. Using a large, recent cohort, we sought to investigate AVN incidence and risk factors, with a special focus on mineral and bone disorders. We conducted a cohort study in 805 patients who underwent KT between 2004 and 2014. AVN was identified in 32 patients (4%): before KT in 15 (1.8%) and after KT in 18 (2.2%) cases, including one patient with both. In the group with post-KT AVN, the median time intervals from KT to 1) first symptoms and 2) AVN diagnosis were 12 months [1-99] and 20 months [4-100], respectively. Being overweight/obese, having pre-transplant diabetes or hyperparathyroidism at transplantation, developing acute rejection, and receiving higher cumulative corticosteroid doses were associated with AVN occurrence. Multivariate analysis revealed that BMI ≥ 26 kg/m2 and higher cumulative corticosteroid doses were predictive of AVN. In conclusion, overweight/obesity is a strong risk factor for AVN. Despite a low maintenance dose, the use of corticosteroids-mostly for treatment of acute rejection-remains an independent risk factor.