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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., Competing Interests: Competing interests: XM received consulting fees from BMS, Novartis, Sanofi, Pfizer, UCB, Janssen, GSK, Galapagos and BMS and is RMD Open associate editor. JE-G received grants from BMS, Lilly, Pfizer (payments made to University of Strasbourg Foundation; no access to TATA data) and consulting fees from BMS, Galapagos, Abbvie, Janssen, Novartis, Pfizer, Sanofi, Gilead, Roche, Chugai and Lilly., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Given the COVID-19 pandemic, it is crucial to understand the underlying behavioural determinants of SARS-CoV-2 vaccine hesitancy in patients with autoimmune or inflammatory rheumatic diseases (AIIRDs). We aimed to analyse patterns of beliefs and intention regarding SARS-CoV-2 vaccination in AIIRD patients, as a mean of identifying pragmatic actions that could be taken to increase vaccine coverage in this population., Methods: Data relating to 1258 AIIRD patients were analysed using univariate and multivariate logistic regression models, to identify variables associated independently with willingness to get vaccinated against SARS-CoV-2. Subsets of patients showing similar beliefs and intention about SARS-CoV-2 vaccination were characterized using cluster analysis., Results: Hierarchical cluster analysis identified three distinct clusters of AIIRD patients. Three predominant patient attitudes to SARS-COV-2 vaccination were identified: voluntary, hesitant and suspicious. While vaccine willingness differed significantly across the three clusters (P < 0.0001), there was no significant difference regarding fear of getting COVID-19 (P = 0.11), the presence of comorbidities (P = 0.23), the use of glucocorticoids (P = 0.21), or immunocompromised status (P = 0.63). However, patients from cluster #2 (hesitant) and #3 (suspicious) were significantly more concerned about vaccination, the use of a new vaccine technology, lack of long-term data in relation to COVID-19 vaccination, and potential financial links with pharmaceutical companies (P < 0.0001 in all) than patients from cluster #1 (voluntary)., Discussion: Importantly, the differences between clusters in terms of patient beliefs and intention was not related to the fear of getting COVID-19 or to any state of frailty, but was related to specific concerns about vaccination. This study may serve as a basis for improved communication and thus help increase COVID-19 vaccine coverage among AIIRD patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The past decade has seen tremendous development in digital health, including in innovative new technologies such as Electronic Health Records, telemedicine, virtual visits, wearable technology and sophisticated analytical tools such as artificial intelligence (AI) and machine learning for the deep-integration of big data. In the field of rare connective tissue diseases (rCTDs), these opportunities include increased access to scarce and remote expertise, improved patient monitoring, increased participation and therapeutic adherence, better patient outcomes and patient empowerment. In this review, we discuss opportunities and key-barriers to improve application of digital health technologies in the field of autoimmune diseases. We also describe what could be the fully digital pathway of rCTD patients. Smart technologies can be used to provide real-world evidence about the natural history of rCTDs, to determine real-life drug utilization, advanced efficacy and safety data for rare diseases and highlight significant unmet needs. Yet, digitalization remains one of the most challenging issues faced by rCTD patients, their physicians and healthcare systems. Digital health technologies offer enormous potential to improve autoimmune rCTD care but this potential has so far been largely unrealized due to those significant obstacles. The need for robust assessments of the efficacy, affordability and scalability of AI in the context of digital health is crucial to improve the care of patients with rare autoimmune diseases., (Copyright © 2021. Published by Elsevier B.V.)

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 < 0.0001). Preventive sick leave had no significant impact on the prevalence of SARS-CoV-2 infection (5.8% [3/53]) compared to work continuation (7.6% [30/397], p = 0.64). Overall, the seroprevalence of SARS-CoV-2 was 6.6% (31/469) which was numerically lower to the Grand-Est general population estimated to be 9.0%., Conclusions: This systematic survey of more than 1000 patients with rare systemic autoimmune diseases reports a low prevalence of proven SARS-CoV-2 infection and very rare severe infections, probably related to good compliance with prophylactic measures in these patients., (© 2021. The Author(s).)

Aim: To describe changes in the 2001-2014 mortality of 6 autoimmune systemic diseases (AISDs), namely Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc), Idiopathic Inflammatory Myopathies (IIM), Sjögren's Syndrome (SS), Mixed Connective Tissue Disease (MCTD) and ANCA-associated vasculitis (AAV) at the country-, continent-, and world-levels., Methods: Mortality data were retrieved from the World Health Organization (WHO) mortality database for each disease, based on ICD-10 codes. We computed age-standardized mortality rate (ASMR) as the estimated number of deaths per million inhabitants and its 95% confidence interval (95%CI). The association between gender, geographical areas and disease-specific mortality was analyzed using multivariate Poisson regression. The 2001-2014 temporal trends were analyzed using Jointpoint software., Results: In 2014, the worldwide ASMR for SLE was 2.68 (95%CI: 2.62-2.75) deaths/millions inhabitants, 1.46 (1.42-1.51) for SSc, 0.47 (0.44-0.49) for IIM, 0.17 (0.15-0.18) for SS, 0.11 (0.10-0.13) for MCTD and 0.53 (0.50-0.56) for AAV, with ASMRs generally lower in Europe than in North America, Latin America and Asia. Between 2001 and 2014, the worldwide ASMR decreased significantly for SSc (-0.71%/year), IIM (-1.65%/year) and AAV (-1.01%/year; p < .001 for all) and increased for SS (+1.53%/year, p = .01). The worldwide ASMR of SLE decreased significantly between 2001 and 2003 (-6.37%, p < .05) before increasing slightly between 2004 and 2014 (+0.58%, p < .01)., Conclusions: We observed a strong heterogeneity of standardized mortality rates across all countries analyzed for 6 autoimmune diseases. Those results further highlight the impact of world-wide inequities and major gaps in access to care and strategies for diagnosis and management of rare diseases, a crucial finding for world-wide physicians, patient associations and policy makers., (Copyright © 2020. Published by Elsevier B.V.)

The myositides are systemic autoimmune conditions of which the most important are polymyositis, dermatomyositis, and inclusion body myositis. In addition to the classic clinical diagnostic criteria, myositis-specific autoantibodies were identified about 15 years ago. Among the dozen or so myositis-specific autoantibodies reported to date, the most characteristic are directed against cytoplasmic antigens, such as tRNA synthetase (Jo-1 or PL-1, PL-7, PL-12, EJ, OJ, JS, and KS), signal-recognition particle (SRP), Mas, KJ, Fer (eEF1), and Wa. Antibodies to nuclear antigens include anti-Mi-2, anti-PMS (PMS1, and PMS2), and related antibodies (MLH1, DNA protein kinase catalytic subunit (DNA PKCS)...), and anti-56 kDa. Myositis-associated antibodies are not specific but may be found in patients with myositis. They are directed to nuclear or nucleolar antigens such as PM-Scl, Ku, RNP (U1-RNP and U2-RNP, U4/U6-RNP, and U5-RNP), Ro 52 kDa and, more rarely, Ro 60 kDa and La. Myositis-specific antibodies have proved useful on two fronts. They have improved the diagnosis of myositis by leading to the identification of characteristic clinical patterns, such as anti-synthetase syndrome. The place of autoantibodies alongside classic clinical and laboratory criteria remains to be determined, however. First, standardized assays will have to be developed to replace current detection methods, which use widely variable techniques and antigen preparations. Myositis-specific antibodies have also shed light on the pathogenesis of myositis. For instance, the development of antibodies to tRNA synthetases constitutes an original autoimmunity model that shows how muscle damage, probably of a nonspecific nature, can lead to the production of autoantibodies that perpetuate and aggravate the muscle lesions.

Subject: After several decades of hegemony of the T lymphocyte, recent work has suggested the importance of the B lymphocyte in auto-immune diseases. As a consequence, there has emerged over the last few years the idea of using anti-B lymphocyte therapy, in particular rituximab (a chimeric anti-CD20 monoclonal antibody)., Current Topics and Important Results: This review addresses various current topics: a) the role of B lymphocytes in auto-immune diseases, notably their capacity to be antigen presenting cells and to be activated by original systems like Blys/Baff; b) the mechanism of action of rituximab (apoptosis, complement-dependent cytotoxicity and antibody-dependent cell cytotoxicity) and the phenomena explaining failures and cases escaping treatment, in particular among lymphoproliferations; c) The results include efficacy and tolerance data for the principal auto-immune affections. Among these, the most promising indications would seem to be for rheumatoid polyarthritis and systemic lupus erythematosis, although some preliminary open studies point to an effect in Goujerot-Sjögren's syndrome, neuropathies, auto-immune cytopenia, idiopathic thrombocytopenic purpura, cryoagglutinins, blistering cutaneous affections..., Perspectives and Projects: Controlled studies will be required to determine the true efficacy and tolerance of this molecule, as it is imperative to validate these new immunotherapeutic strategies, above all when they concern innovative and expensive therapy. Nevertheless, these different observations arouse great hopes and at the same time exciting questions, notably as to the role of B lymphocytes in auto-immune diseases.