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Concerns have been raised about the reduced immunogenicity of vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory diseases and the higher risk of breakthrough infections. The objective of our study was to investigate the intensity and longevity of SARS-CoV-2 vaccination responses in patients with immune-mediated inflammatory diseases, and to assess the effects of diagnosis, treatment, and adapted vaccination schedules.SARS-CoV-2 IgG antibody response after SARS-CoV-2 vaccination was measured over time in a large prospective cohort of healthy controls and participants with immune-mediated inflammatory diseases (attending or admitted to affiliated centres) between Dec 15, 2020, and Dec 1, 2021. Cohort participants with immune-mediated inflammatory diseases and control participants with no diagnosis of immune-mediated inflammatory diseases, were eligible for this analysis. Demographic data and disease-specific data were collected using a questionnaire. Humoral response was compared across treatment and disease groups, and with respect to the receipt of additional vaccinations. SARS-CoV-2 antibody response was measured by ELISA using optical density ratio units and modelled over time with age and sex adjustment using mixed-effects models. Using these models, marginal mean antibody titres and marginal risks of a poor response (optical density ratio1·1) were calculated for each week starting from week 8 after the first vaccination to week 40.Among 5076 individuals registered, 2535 participants with immune-mediated inflammatory diseases (mean age 55·0 [15·2] years; 1494 [58·9%] women and 1041 [41·1%] men) and 1198 healthy controls (mean age 40·7 [13·5] years; 554 [46·2%] women and 644 [53·8%] men) were included in this analysis. Mean antibody titres were higher in healthy controls compared with people with immune-mediated inflammatory diseases at all timepoints, with a peak antibody response in healthy controls (mean optical density ratio 12·48; 95% CI 11·50-13·53) of more than twice that in participants with immune-mediated inflammatory diseases (5·50; 5·23-5·77; mean difference 6·98; 5·92-8·04). A poor response to vaccination was observed in participants with immune-mediated inflammatory diseases who were taking B-cell inhibitors (peak mean difference from healthy controls 11·68; 10·07-13·29) and T-cell inhibitors (peakmean difference from healthy controls 10·43; 8·33-12·53). Mean differences in antibody responses between different immune-mediated inflammatory diseases were small. Participants with immune-mediated inflammatory diseases who were given a third vaccine dose had higher mean antibody titres than did healthy controls vaccinated with two vaccine doses at 40 weeks after the initial vaccination (mean difference 1·34; 0·01-2·69).People with immune-mediated inflammatory diseases show a lower and less durable SARS-CoV-2 vaccination response and are at risk of losing humoral immune protection. Adjusted vaccination schedules with earlier booster doses or more frequent re-doses, or both, could better protect people with immune-mediated inflammatory diseases.Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, European Research Council, Innovative Medicine Initiative, Friedrich-Alexander-Universität Erlangen-Nürnberg, Else Kröner-Memorial Foundation.

Patients with immune-mediated diseases (IMID) such as systemic sclerosis (SSc), who are treated with B cell depleting treatments, are at risk for developing severe COVID-19 due to inadequate humoral immune response. During B cell depletion, therapeutic substitution of neutralizing monoclonal antibodies against the SARS-CoV-2 spike protein (mAbs) might be helpful to prevent severe COVID-19. It has been shown, that in non-IMID patients mABs reduce SARS-CoV-2 viral load and lower the risk of COVID-19 associated hospitalization or death. However, there are limited data on the effect of mAbs in IMID patients after exposure, especially in patients treated with B cell depleting agents. Herein, we report a case of a rituximab treated SSc patient who developed COVID-19 and was successfully treated with a combination of mAbs (casirivimab/imdevimab). With this case we show that IMID patients may benefit from post-exposure administration of mAbs. In our case treatment with neutralizing autoantibodies was safe and a possible contributor in protecting the patient from mechanical ventilation and eventually death. We frame this case within the current evidence from the literature and provide a perspective on the future potential role of mAbs for treating IMID patients suffering from COVID-19.

Einleitung: Ältere Patienten mit rheumatoider Arthritis (RA) haben ein höheres Risiko für schwerwiegende Infektionen (SI). Gleichzeitig ist die Therapie mit bDMARDs mit einem höheren Risiko für SI im Vergleich zur Therapie mit csDMARDs assoziiert [ref:1]. Daten einer[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Rheumatologiekongress 2021, 49. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 35. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), Wissenschaftliche Herbsttagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Objective B cell depletion is an established therapeutic principle in a wide range of autoimmune disease. However, B cells are also critical for inducing protective immunity after infection and vaccination. We therefore assessed humoral and cellular immune responses after infection with or vaccination against severe acute respiratory syndrome coronavirus ‐2 (SARS‐CoV‐2) in B cell depleted patients and B cell competent healthy controls. Methods Antibody (ELISA) and T cell (IFNγ ELISPOT) responses against the SARS‐CoV‐2 spike S1 and nucleocapsid proteins were assessed in a limited number of infected (N=6) and vaccinated (N=8) B cell depleted autoimmune patients as well as infected (N=30) and vaccinated (N=30) healthy controls. Results As expected, B and T cell responses to the nucleocapsid were observed only after infection, while respective responses to spike S1 were found both after infection and vaccination. A SARS‐CoV‐2 antibody response was observed in all vaccinated controls (30/30, 100%) but in none (0/8) of the vaccinated B‐cell‐depleted patients. In contrast, after SARS‐CoV‐2 infection, both B‐cell‐depleted patients (spike S: 5/6, 83%; nucleocapsid 3/6, 50%) and healthy controls (spike S: 28/30, 94%; nucleocapsid 28/30, 93%) developed antibodies. T cell responses against the spike S1 and nucleocapsid proteins were found in both infected and vaccinated B cell depleted subjects and in the controls. Conclusion These data show that B cell depletion completely blocks humoral but not T cell SARS‐CoV‐2 vaccination response. Furthermore, limited humoral immune responses are found in B cell depleted patients after SARS‐CoV‐2 infection.

Background Biological disease-modifying anti-rheumatic drugs (bDMARDs) can be tapered in some rheumatoid arthritis (RA) patients in sustained remission. The purpose of this study was to assess the feasibility of building a model to estimate the individual flare probability in RA patients tapering bDMARDs using machine learning methods. Methods Longitudinal clinical data of RA patients on bDMARDs from a randomized controlled trial of treatment withdrawal (RETRO) were used to build a predictive model to estimate the probability of a flare. Four basic machine learning models were trained, and their predictions were additionally combined to train an ensemble learning method, a stacking meta-classifier model to predict the individual flare probability within 14 weeks after each visit. Prediction performance was estimated using nested cross-validation as the area under the receiver operating curve (AUROC). Predictor importance was estimated using the permutation importance approach. Results Data of 135 visits from 41 patients were included. A model selection approach based on nested cross-validation was implemented to find the most suitable modeling formalism for the flare prediction task as well as the optimal model hyper-parameters. Moreover, an approach based on stacking different classifiers was successfully applied to create a powerful and flexible prediction model with the final measured AUROC of 0.81 (95%CI 0.73–0.89). The percent dose change of bDMARDs, clinical disease activity (DAS-28 ESR), disease duration, and inflammatory markers were the most important predictors of a flare. Conclusion Machine learning methods were deemed feasible to predict flares after tapering bDMARDs in RA patients in sustained remission. Supplementary Information The online version contains supplementary material available at 10.1186/s13075-021-02439-5.

Einleitung: Gewebeschäden bei nicht-malignen Erkrankungen des Menschen können entweder durch übermäßige Entzündung oder durch überschießende fibrotische Reaktionen verursacht werden. Die molekularen und zellulären Grundlagen dieser beiden Prozesse, ihre Auswirkungen[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Rheumatologiekongress 2020, 48. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 34. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)

Vorgeschichte: Ein 55-jähriger Patient mit bekannter Psoriasis-Arthritis unter Methotrexat- und Leflunomid-Therapie, wurde zur weiteren Abklärung von etwa seit 5 Monaten bestehendem trockenen Husten, Belastungsdyspnoe, ausgeprägtem Nachtschweiß, starker Abgeschlagenheit und intermittierendem[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Rheumatologiekongress 2020, 48. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 34. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)

Einleitung: Die Chondrokalzinose ist eine entzündliche Erkrankung der Gelenke, die durch die Ablagerung von Kalziumpyrophosphatkristallen in den betroffenen Geweben ausgelöst wird. Diese Kristalle wirken ähnlich wie Harnsäurekristalle als Gefahrensignal (Danger Associated Molecular[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Rheumatologiekongress 2020, 48. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 34. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)