388 results on '"Martin Aringer"'
Search Results
2. P6 Increased interleukin-6 (IL-6) receptor shedding under interferon-α and IL-6 explains the relatively low C-reactive protein (CRP) levels in SLE patients
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Martin Aringer, Nicolai Leuchten, Adelheid Korb-Pap, Babett Heschel, Annika Krause, Martyna Hempel, Erik Klapproth, and Ali El-Amouche
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2024
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3. I12 EULAR/ACR SLE classification criteria: 5 years later
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Martin Aringer
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2024
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4. Severe methotrexate toxicity in elderly patients under diuretics
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Martin Aringer, Nicolai Leuchten, Kristine Herrmann, Cara Kumar, and Matthias Kuhn
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Medicine - Abstract
Objectives To explore the toxicity of low-dose methotrexate (MTX), an uncommon, but life-threatening event.Methods We analysed the presentation, course and risk factors of all patients admitted to the rheumatology ward with severe low-dose MTX toxicity. These patients were compared with patients without signs of relevant MTX toxicity.Results The 12 patients admitted for MTX toxicity included 7 patients with rheumatoid arthritis, 2 with psoriatic arthritis or psoriasis, 2 patients with giant cell arteritis and 1 with myositis. 1 patient died from infections, while 11 survived under folinic acid administration. All patients suffering from severe MTX toxicity were older than 70 years and were therefore compared with 400 patients who were also older than 70 years, but without MTX toxicity. Of these 400 control patients, the group of patients not on MTX (n=232) had more renal impairment than the group of patients on MTX (n=168). Compared with the 168 MTX-treated patients without toxicity, the 12 patients with life-threatening toxic events had a lower median estimated glomerular filtration rate (eGFR) at the routine visit preceding the acute event (64 (range 32–77) vs 69 (range 8 to >90) mL/min x 1.73, p=0.0251). A multivariate analysis found that patients with toxicity were more frequently treated with diuretics (6/12 vs 24/168), proton pump inhibitors (PPIs; 10/12 vs 70/168) and levetiracetam (2/12 vs 1/168).Conclusions Patients older than 70 years with lower eGFR and being on diuretics, but also on PPIs and levetiracetam, have a significantly higher risk for MTX toxicity.
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- 2024
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5. Case Report: Response of cutaneous lupus lesions in SLE to interferon receptor blockade parallels reduction of interferon score in blood
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Claudia Günther, Christine Wolf, Louisa Fennen, Sarah Rösing, Stefan Beissert, Martin Aringer, and Min Ae Lee-Kirsch
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interferon ,IFN score ,cutaneous lupus ,anifrolumab ,CLASI ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Cutaneous lupus erythematosus (CLE), the main manifestation of systemic lupus erythematosus (SLE), is driven by type I interferons (IFNs) and often only partially responds to conventional therapies. Treatment of seven SLE patients with the monoclonal antibody anifrolumab induced fast and sustained remission of previously refractory CLE lesions, beginning within the first weeks of treatment. Decline in CLASI-A score was paralleled by a reduction in IFN score determined by mRNA expression of seven IFN-stimulated genes (ISGs) in blood. These data suggest that a subset of ISGs could be a valuable biomarker in CLE.
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- 2023
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6. Burden of systemic lupus erythematosus in clinical practice: baseline data from the SLE Prospective Observational Cohort Study (SPOCS) by interferon gene signature
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Richard Furie, Raj Tummala, Laurent Arnaud, Eric F Morand, Martin Aringer, Barnabas Desta, Bo Ding, Christine Peschken, Jacob Knagenhjelm, Heide A Stirnadel-Farrant, Eleni Rapsomaniki, Jonatan Hedberg, Caroline Seo, Tina Grünfeld Eén, and Alessandro Sorrentino
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Objective The longitudinal Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS) aims to assess SLE disease course overall and according to type I interferon 4 gene signature (IFNGS). Here, we describe SPOCS patient characteristics by IFNGS and baseline disease activity.Methods SPOCS (NCT03189875) is an international study of patients with SLE according to Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) criteria. Enrolled patients from 135 centres in 8 countries were followed biannually for ≤3 years from June 2017 to November 2022. Baseline demographics, disease characteristics, organ system involvement/damage and flares were analysed descriptively according to SLE Disease Activity Index-2000 score (SLEDAI-2K
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- 2023
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7. Remission Possible: New Era of SLE Treatment with Biologics Involvement
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Martin Aringer
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Treat-to-target (T2T) is a therapeutic approach used in several rheumatologic disorders such as rheumatoid arthritis, gout, axial spondylarthritis, and other inflammatory diseases such as inflammatory bowel disease. Developing a T2T strategy for systemic lupus erythematosus (SLE) has been difficult due to the complexity of the disease. The 2019 EULAR recommendations for the management of SLE, reestablished in the 2023 EULAR guideline, specified that the primary treatment goal should be remission or the lowest possible disease activity. In SLE, remission is associated with reduced organ damage, fewer flares, reduced hospitalisation, reduced mortality, and improved health-related quality of life. Previously remission in SLE was seen as an unattainable goal; however, the treatment landscape for SLE has evolved, and recent advancements, particularly the use of biologics, have emerged as promising therapeutic options to improve patient outcomes. A new post-hoc analysis of the TULIP Phase III programme provides evidence across four years that remission is an achievable goal with anifrolumab, a type I interferon (IFN) receptor antagonist for adult patients with moderate to severe (SLE) who are receiving standard therapy. At Week 208, 30.3% (n=58/194) of patients treated with anifrolumab were in remission compared with 18.3% (n=12/65) of those in the standard therapy alone group. This was an increase from 19.7% (n=49/251) of patients treated with anifrolumab who achieved remission at the first LTE visit (Week 64) compared with 9.9% (n=10/104) of those in the standard therapy alone group. Treatment with anifrolumab was also associated with more frequent, prolonged, and sustained DORIS remission attainment compared with placebo during the 4-year TULIP+LTE period. Real-world case studies have also illustrated the effectiveness of biologics in controlling disease activity, enhancing quality of life, and establishing long-term safety profiles. In conclusion, biologic therapies have emerged as a valuable treatment option for achieving remission or lupus low disease activity state. Biologics has opened a new era revolutionizing the management of SLE, offering renewed hope for patients living with this challenging autoimmune disease.
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- 2024
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8. Characteristics and outcomes of SARS-CoV-2 breakthrough infections among double-vaccinated and triple-vaccinated patients with inflammatory rheumatic diseases
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Tobias Alexander, Hendrik Schulze-Koops, Ulf Müller-Ladner, Rebecca Fischer-Betz, Martin Aringer, Rieke Alten, Petra Saar, Tim Schmeiser, Marina Backhaus, Stephanie Finzel, Cornelia Glaser, Hildrun Haibel, Hanns-Martin Lorenz, Gamal Chehab, Christof Specker, Reinhard E Voll, Anja Strangfeld, Norbert Blank, Matthias Braun, Alexander Pfeil, Rebecca Hasseli, Andreas Krause, Anne Constanze Regierer, Peer Aries, Ioana Andreica, Jacqueline Detert, Elvira Decker, Urs Hartmann, Joerg Henes, Kirsten de Groot, JOACHIM GEORGI, Hans Bastian, Christoph Fiehn, Martin Feuchtenberger, Martin Fleck, Christian Blum, Mathias Grunke, Martin Bohl-Bühler, Georg Gauler, Bimba Franziska Hoyer, Guido Hoese, Janine Günther, Matthias Braunisch, Jutta G. Richter, Sabine Reckert, Anett Gräßler, Andreas Kapelle, Silke Osiek, Anna Knothe, Jan Brandt-Jürgens, Anja Maltzahn, Fredrik Albach, Annette Alberding, Susanne Aman, Christopher Amberger, Michaela Amberger, Bianka Andermann, Nils Anders, Jan Andresen, Nikolaos Andriopoulos, Elizabeth Arauj, Uta Arndt, Sarah Avemarg, Christoph Baerwald, Erich Bärlin, Nora Bartholomä, Michael Bäuerle, Jutta Bauhammer, Christine Baumann, Klaus Becker, Heidemarie Becker, Michaela Bellm, Sylvia Berger, Andrea Berghofen, Gerhard Birkner, Daniel Blendea, Hans Bloching, Sebastian Blötz, Stephanie Boeddeker, Susanne Bogner, Lara Bohnen, Ilka Bösenberg, Nicole Böttcher, Diana Braun, Jan Philipp Bremer, Matthias Broll, Andreas Bruckner, Veronika Brumberger, Martin Brzank, Sahra Büllesfeld, Sandra Burger, Michaela Christenn, Anne Claußnitzer, Frank Demtröder, Rainer Dörfler, Elke Drexler, Valeria Dudics, Edmund Edelmann, Roman Eder, Christina Eisterhues, Joachim Michael Engel, Brigitte Erbslöh-Möller, Miriam Feine, Samantha Ferdinan, Claudia Franke, Stefanie Freudenberg, Christian Fräbel, Petra Fuchs, Regina Gaissmaier, Ino Gao, Oliver Gardt, Katrin Geißler, Karolina Gente, Jasmin Gilly, Yannik Gkanatsas, Agnes Gniezinski- Schwister, Rahel Gold, Norman Görl, Ralf Görlitz, Karl-Heinz Göttl, Beate Göttle, Ricardo Grieshaber Bouyer, Gisela Grothues, Florian Günther, Mirjam Haag, Linda Haas, Anna Haas-Wöhrle, Denitsa Hadjiski, Till Hallmann-Böhm, Peter Härle, Charlotte Hasenkamp, Maura-Maria Hauf, and Matthias Hauser
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Medicine - Abstract
Objective To analyse the clinical profile of SARS-CoV-2 breakthrough infections in at least double-vaccinated patients with inflammatory rheumatic diseases (IRDs).Methods Data from the physician-reported German COVID-19-IRD registry collected between February 2021 and July 2022 were analysed. SARS-CoV-2 cases were stratified according to patients’ vaccination status as being not vaccinated, double-vaccinated or triple-vaccinated prior to SARS-CoV-2 infection and descriptively compared. Independent associations between demographic and disease features and outcome of breakthrough infections were estimated by multivariable logistic regression.Results In total, 2314 cases were included in the analysis (unvaccinated n=923, double-vaccinated n=551, triple-vaccinated n=803, quadruple-vaccinated n=37). SARS-CoV-2 infections occurred after a median of 151 (range 14–347) days in patients being double-vaccinated, and after 88 (range 14–270) days in those with a third vaccination. Hospitalisation was required in 15% of unvaccinated, 8% of double-vaccinated and 3% of triple-vaccinated/quadruple-vaccinated patients (p
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- 2023
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9. Is the Rheumatoid Arthritis Impact of Disease (RAID) score a meaningful instrument for other inflammatory rheumatic diseases? A cross-sectional analysis of data from the German National Database
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Angela Zink, Johanna Callhoff, Martin Aringer, Katinka Albrecht, Katja Thiele, Susanna Späthling-Mestekemper, Ulrich von Hinüber, and Kirsten Karberg
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Medicine - Abstract
ObjectiveTo analyse the performance of the rheumatoid arthritis impact of disease (RAID) score in patients with ankylosing spondylitis, polymyalgia rheumatica, systemic lupus erythematosus, primary Sjögren’s syndrome, idiopathic inflammatory myositis and systemic sclerosis, as compared with rheumatoid arthritis (RA).MethodsA total of 12 398 patients from the German National Database were included. For each diagnosis, we calculated age-adjusted/sex-adjusted partial correlation coefficients between RAID and patient global (PtGl) health, PtGl disease activity, physician global (PhGl) disease activity, Well-Being Index (WHO-5) and EuroQoL-5 Dimensions (EQ-5D). As a measure of agreement, the mean differences between the RAID and other outcomes were compared with the respective differences for RA. The effect of each diagnosis on the difference between RAID and the other scores was assessed with linear regression, with RA as the reference.ResultsAcross all diagnoses, RAID correlated strongly with PtGl health (0.71–0.83), moderately to strongly with PtGl disease activity (0.59–0.79), WHO-5 (0.65–0.81) and EQ-5D (0.68–0.73) and weakly with PhGl disease activity (0.23–0.38). Mean differences were calculated for RAID and PtGl disease activity (0 to −0.6), PtGl health (−0.4 to −0.9), WHO-5 (−0.7 to −1.3), EQ-5D (1.1 to 1.7) and PhGl disease activity (1.4 to 2.2). Discrepancies between other scores and RAID were comparable to RA. Linear regression revealed no clinically relevant effect of any of the diagnoses on the difference between RAID and the other outcomes.ConclusionThe RAID score performs comparably across all diagnoses investigated. This supports the use of RAID for measuring the impact also of other rheumatic diseases.
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- 2022
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10. A glimpse into the future of systemic lupus erythematosus
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Martin Aringer, Marta E. Alarcón-Riquelme, Megan Clowse, Guillermo J. Pons-Estel, Edward M. Vital, and Maria Dall’Era
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
This viewpoint article on a forecast of clinically meaningful changes in the management of systemic lupus erythematosus (SLE) in the next 10 years is based on a review of the current state of the art. The groundwork has been laid by a robust series of classification criteria and treatment recommendations that have all been published since 2019. Building on this strong foundation, SLE management predictably will take significant steps forward. Assessment for lupus arthritis will presumably include musculoskeletal sonography. Large-scale polyomics studies are likely to unravel more of the central immune mechanisms of the disease. Biomarkers predictive of therapeutic success may enter the field; the type I interferon signature, as a companion for use of anifrolumab, an antibody against the common type I interferon receptor, is one serious candidate. Besides anifrolumab for nonrenal SLE and the new calcineurin inhibitor voclosporin in lupus nephritis, both of which are already approved in the United States and likely to become available in the European Union in 2022, several other approaches are in advanced clinical trials. These include advanced B cell depletion, inhibition of costimulation via CD40 and CD40 ligand (CD40L), and Janus kinase 1 (Jak1) and Tyrosine kinase 2 (Tyk2) inhibition. At the same time, essentially all of our conventional therapeutic armamentarium will continue to be used. The ability of patients to have successful SLE pregnancies, which has become much better in the last decades, should further improve, with approaches including tumor necrosis factor blockade and self-monitoring of fetal heart rates. While we hope that the COVID-19 pandemic will soon be controlled, it has highlighted the risk of severe viral infections in SLE, with increased risk tied to certain therapies. Although there are some data that a cure might be achievable, this likely will remain a challenge beyond 10 years from now.
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- 2022
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11. 2021 DORIS definition of remission in SLE: final recommendations from an international task force
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Victoria P Werth, Ronald F van Vollenhoven, Laurent Arnaud, Ricard Cervera, Andrea Doria, Angela Tincani, Matthias Schneider, Marta Mosca, Nathalie Costedoat-Chalumeau, Cynthia Aranow, Michelle A Petri, Ian N Bruce, Dimitrios T Boumpas, Michael M Ward, Manuel Francisco Ugarte-Gil, Bernardo A Pons-Estel, Ann Elaine Clarke, Juanita Romero-Diaz, Caroline Gordon, Sang-Cheol Bae, Anisur Rahman, Murat Inanc, Søren Jacobsen, George Bertsias, Xavier Mariette, Thomas Dörner, Hendrika Bootsma, Josef Smolen, Mandana Nikpour, David Jayne, Martin Aringer, David Isenberg, László Czirják, Annegret Kuhn, Y K Onno Teng, Frédéric A Houssiau, Hermine Brunner, Eric Morand, Carlos Vasconcelos, Guillermo Pons-Estel, Graciela Alarcon, Eloisa Bonfa, Alexandre Voskuyl, Raquel Faria, Anne Voss, Maarten Limper, Anca D Askanase, Sandra Navarra, Cindy Coney, Ruth Fritsch-Stork, Bernadette van Leeuw, Michel Tsang-a-Sjoe, Rebecca Fischer, Marzena Helena Olesinska, Blanca Rubio, Yehuda Schoenfeld, and Elena Zakharhova
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2021
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12. Comorbidity and healthcare utilisation in persons with incident systemic lupus erythematosus followed for 3 years after diagnosis: analysis of a claims data cohort
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Johanna Callhoff, Martin Aringer, Katinka Albrecht, Imke Redeker, and Ursula Marschall
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2021
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13. Induction of sustained remission in early inflammatory arthritis with the combination of infliximab plus methotrexate: the DINORA trial
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Tanja Alexandra Stamm, Klaus Peter Machold, Daniel Aletaha, Farideh Alasti, Peter Lipsky, David Pisetsky, Robert Landewe, Desiree van der Heijde, Alexandre Sepriano, Martin Aringer, Dimitri Boumpas, Gerd Burmester, Maurizio Cutolo, Wolfgang Ebner, Winfried Graninger, Tom Huizinga, Georg Schett, Hendrik Schulze-Koops, Paul-Peter Tak, Emilio Martin-Mola, Ferdinand Breedveld, and Josef Smolen
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Clinical remission ,Early arthritis ,Rheumatoid arthritis ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background In the present study, we explored the effects of immediate induction therapy with the anti-tumour necrosis factor (TNF)α antibody infliximab (IFX) plus methotrexate (MTX) compared with MTX alone and with placebo (PL) in patients with very early inflammatory arthritis. Methods In an investigator-initiated, double-blind, randomised, placebo-controlled, multi-centre trial (ISRCTN21272423, http://www.isrctn.com/ISRCTN21272423), patients with synovitis of 12 weeks duration in at least two joints underwent 1 year of treatment with IFX in combination with MTX, MTX monotherapy, or PL randomised in a 2:2:1 ratio. The primary endpoint was clinical remission after 1 year (sustained for at least two consecutive visits 8 weeks apart) with remission defined as no swollen joints, 0–2 tender joints, and an acute-phase reactant within the normal range. Results Ninety patients participated in the present study. At week 54 (primary endpoint), 32% of the patients in the IFX + MTX group achieved sustained remission compared with 14% on MTX alone and 0% on PL. This difference (p
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- 2018
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14. New insights into the prevalence of depressive symptoms and depression in rheumatoid arthritis - Implications from the prospective multicenter VADERA II study.
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Matthias Englbrecht, Rieke Alten, Martin Aringer, Christoph G Baerwald, Harald Burkhardt, Nancy Eby, Jan-Paul Flacke, Gerhard Fliedner, Ulf Henkemeier, Michael W Hofmann, Stefan Kleinert, Christian Kneitz, Klaus Krüger, Christoph Pohl, Georg Schett, Marc Schmalzing, Anne-Kathrin Tausche, Hans-Peter Tony, and Jörg Wendler
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Medicine ,Science - Abstract
ObjectivesTo investigate the prevalence of depressive symptoms in rheumatoid arthritis (RA) patients using two previously validated questionnaires in a large patient sample, and to evaluate depressive symptoms in the context of clinical characteristics (e.g. remission of disease) and patient-reported impact of disease.MethodsIn this cross-sectional study, the previously validated Patient Health Questionnaire (PHQ-9) and Beck-Depression Inventory II (BDI-II) were used to assess the extent of depressive symptoms in RA patients. Demographic background, RA disease activity score (DAS28), RA impact of disease (RAID) score, comorbidities, anti-rheumatic therapy and antidepressive treatment, were recorded. Cut-off values for depressive symptomatology were PHQ-9 ≥5 or BDI-II ≥14 for mild depressive symptoms or worse and PHQ-9 ≥ 10 or BDI-II ≥ 20 for moderate depressive symptoms or worse. Prevalence of depressive symptomatology was derived by frequency analysis while factors independently associated with depressive symptomatology were investigated by using multiple logistic regression analyses. Ethics committee approval was obtained, and all patients provided written informed consent before participation.ResultsIn 1004 RA-patients (75.1% female, mean±SD age: 61.0±12.9 years, mean disease duration: 12.2±9.9 years, DAS28 (ESR): 2.5±1.2), the prevalence of depressive symptoms was 55.4% (mild or worse) and 22.8% (moderate or worse). Characteristics independently associated with depressive symptomatology were: age 2 (OR = 10.54) and presence of chronic pain (OR = 3.25). Of patients classified as having depressive symptoms, only 11.7% were receiving anti-depressive therapy.ConclusionsMild and moderate depressive symptoms were common in RA patients according to validated tools. In routine clinical practice, screening for depression with corresponding follow-up procedures is as relevant as incorporating these results with patient-reported outcomes (e.g. symptom state), because the mere assessment of clinical disease activity does not sufficiently reflect the prevalence of depressive symptoms.Clinical trial registration numberThis study is registered in the Deutsches Register Klinischer Studien (DRKS00003231) and ClinicalTrials.gov (NCT02485483).
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- 2019
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15. Recent advances in managing systemic sclerosis [version 1; referees: 2 approved]
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Martin Aringer and Anne Erler
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Autoimmunity ,Cardiovascular Pharmacology ,Cutaneous Signs of Systemic Disease ,Dermatologic Pharmacology ,Immune & Inflammatory Rheumatic Diseases (incl. Arthritis) ,Immunopharmacology & Hematologic Pharmacology ,Interstitial Lung Diseases ,Pulmonary Vascular Diseases ,Respiratory Pharmacology ,Urticaria, Vasculitis & Connective Tissue Disease ,Vascular Diseases (Non-Coronary) ,Medicine ,Science - Abstract
How the main components in systemic sclerosis—namely autoimmunity, vasculopathy, and fibrosis—fit together is still not sufficiently clear. However, vascular treatment options are well established, the body of evidence for the efficacy of immunomodulatory approaches is increasing, and now at least one hopeful substance that may directly interfere with fibrosis is being tested. Although we still wait for important breakthroughs, there is grounds for hope that better therapeutic options will be available in the near future.
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- 2017
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16. Tophaceous Gout and Renal Insufficiency: A New Solution for an Old Therapeutic Dilemma
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Anne-Kathrin Tausche, Carsten Wunderlich, and Martin Aringer
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Medicine - Abstract
The prevalence of gout is increasing with increased life expectancy. Approximately half of the patients with gout have some degree of renal impairment. If both conditions persistently coexist, and in severe tophaceous gout, in particular, treatment has been difficult. We here report on the case of an 87-year-old woman, who had been suffering from recurrent gouty arthritis over 4 years. Monthly polyarthritis attacks were accompanied by subcutaneous tophi. Serum uric acid levels were constantly above 600 μmol/L (10 mg/dL). Allopurinol was no option because of intolerance, while benzbromarone was ineffective because of renal impairment. Therefore, the novel xanthin oxidase inhibitor febuxostat was started, achieving rapid control of serum urate levels (
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- 2011
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17. Praktikable Sjögren-Diagnostik bei interstitieller Lungenerkrankung – ein Diskussionsbeitrag
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Martin Aringer, Dirk Koschel, Thomas Dörner, Philipp Sewerin, Antje Prasse, and Torsten Witte
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Rheumatology - Abstract
ZusammenfassungDas Sjögren-Syndrom (SjS) stellt eine mögliche autoimmune Ursache einer interstitiellen Lungenerkrankung dar. Die Abklärung in Richtung SjS ist aber im Vergleich zu anderen systemischen Autoimmunerkrankungen bisher kaum standardisiert. Die subjektive Sicca-Symptomatik, die Anti-SS-A/Ro-Antikörper und selbst die ANA-Diagnostik als Suchtest haben alle relevante Einschränkungen in ihrer Sensitivität und/oder Spezifität. Vor diesem Hintergrund haben wir in einer interdisziplinären Diskussion einen Konsens für die SjS-Abklärung entwickelt, den wir hier für die breitere Diskussion vorstellen. Neben ANA sollten sowohl Anti-SS-A/Ro-Antikörper als auch Antikörper gegen α‑Fodrin bestimmt werden. Wichtig ist die Objektivierung der Trockenheit mittels Schirmer- und Saxon-Test und bei fehlenden typischen Autoantikörpern die Speicheldrüsenbiopsie.
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- 2023
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18. Evaluation of the <scp>EULAR</scp> /American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus in a <scp>Population‐Based</scp> Registry
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Allison Guttmann, Brendan Denvir, Martin Aringer, Jill P. Buyon, H. Michael Belmont, Sara Sahl, Jane E. Salmon, Anca Askanase, Joan M. Bathon, Laura Geraldino‐Pardilla, Yousaf Ali, Ellen M. Ginzler, Chaim Putterman, Caroline Gordon, Charles G. Helmick, Hilary Parton, and Peter M. Izmirly
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Rheumatology - Published
- 2023
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19. Updating the core domains set in Systemic Lupus Erythematosus: Work planned by the Systemic Lupus Erythematosus OMERACT working group
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Wils Nielsen, Vibeke Strand, Lee S Simon, Julian Thumboo, Marta Mosca, Martin Aringer, Eric F Morand, Ian Bruce, and Zahi Touma
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Rheumatology - Published
- 2023
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20. Improvement of cutaneous inflammation and panniculitis in patients with dermatomyositis by the Janus kinase inhibitor baricitinib
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Kristina Fischer, Martin Aringer, Julian Steininger, Julius Heil, Stefan Beissert, Susanne Abraham, and Claudia Günther
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Inflammation ,Sulfonamides ,Panniculitis ,Purines ,Azetidines ,Humans ,Janus Kinase Inhibitors ,Pyrazoles ,Janus Kinase 1 ,Dermatology ,Janus Kinase 2 ,Dermatomyositis - Published
- 2022
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21. Anifrolumab für die Therapie des systemischen Lupus erythematodes
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Martin Aringer and Sirka Nitschmann
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- 2022
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22. Effect of nintedanib in patients with progressive pulmonary fibrosis associated with rheumatoid arthritis: data from the INBUILD trial
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Eric L. Matteson, Martin Aringer, Gerd R. Burmester, Heiko Mueller, Lizette Moros, and Martin Kolb
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Rheumatology ,General Medicine - Abstract
Objectives Some patients with rheumatoid arthritis develop interstitial lung disease (RA-ILD) that develops into progressive pulmonary fibrosis. We assessed the efficacy and safety of nintedanib versus placebo in patients with progressive RA-ILD in the INBUILD trial. Methods The INBUILD trial enrolled patients with fibrosing ILD (reticular abnormality with traction bronchiectasis, with or without honeycombing) on high-resolution computed tomography of >10% extent. Patients had shown progression of pulmonary fibrosis within the prior 24 months, despite management in clinical practice. Subjects were randomised to receive nintedanib or placebo. Results In the subgroup of 89 patients with RA-ILD, the rate of decline in FVC over 52 weeks was −82.6 mL/year in the nintedanib group versus −199.3 mL/year in the placebo group (difference 116.7 mL/year [95% CI 7.4, 226.1]; nominal p = 0.037). The most frequent adverse event was diarrhoea, which was reported in 61.9% and 27.7% of patients in the nintedanib and placebo groups, respectively, over the whole trial (median exposure: 17.4 months). Adverse events led to permanent discontinuation of trial drug in 23.8% and 17.0% of subjects in the nintedanib and placebo groups, respectively. Conclusions In the INBUILD trial, nintedanib slowed the decline in FVC in patients with progressive fibrosing RA-ILD, with adverse events that were largely manageable. The efficacy and safety of nintedanib in these patients were consistent with the overall trial population. A graphical abstract is available at: https://www.globalmedcomms.com/respiratory/INBUILD_RA-ILD. Key Points• In patients with rheumatoid arthritis and progressive pulmonary fibrosis, nintedanib reduced the rate of decline in forced vital capacity (mL/year) over 52 weeks by 59% compared with placebo.• The adverse event profile of nintedanib was consistent with that previously observed in patients with pulmonary fibrosis, characterised mainly by diarrhoea.• The effect of nintedanib on slowing decline in forced vital capacity, and its safety profile, appeared to be consistent between patients who were taking DMARDs and/or glucocorticoids at baseline and the overall population of patients with rheumatoid arthritis and progressive pulmonary fibrosis.
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- 2023
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23. Assessment-Tools für den systemischen Lupus erythematodes
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Martin Aringer and Nicolai Leuchten
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Rheumatology - Published
- 2023
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24. Nintedanib in Patients With Autoimmune Disease–Related Progressive Fibrosing Interstitial Lung Diseases: Subgroup Analysis of the <scp>INBUILD</scp> Trial
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Eric L, Matteson, Clive, Kelly, Jörg H W, Distler, Anna-Maria, Hoffmann-Vold, James R, Seibold, Shikha, Mittoo, Paul F, Dellaripa, Martin, Aringer, Janet, Pope, Oliver, Distler, Alexandra, James, Rozsa, Schlenker-Herceg, Susanne, Stowasser, Manuel, Quaresma, and Kevin R, Flaherty
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Indoles ,Rheumatology ,Vital Capacity ,Immunology ,Disease Progression ,Humans ,Immunology and Allergy ,Lung Diseases, Interstitial ,Protein Kinase Inhibitors ,Idiopathic Pulmonary Fibrosis ,Autoimmune Diseases - Abstract
To analyze the efficacy and safety of nintedanib in patients with fibrosing autoimmune disease-related interstitial lung diseases (ILDs) with a progressive phenotype.The INBUILD trial enrolled patients with a fibrosing ILD other than idiopathic pulmonary fibrosis, with diffuse fibrosing lung disease of10% extent on high-resolution computed tomography, forced vital capacity percent predicted (FVC%) ≥45%, and diffusing capacity of the lungs for carbon monoxide percent predicted ≥30% to80%. Patients fulfilled protocol-defined criteria for progression of ILD within the 24 months before screening, despite management deemed appropriate in clinical practice. Subjects were randomized to receive nintedanib or placebo. We assessed the rate of decline in FVC (ml/year) and adverse events (AEs) over 52 weeks in the subgroup with autoimmune disease-related ILDs.Among 170 patients with autoimmune disease-related ILDs, the rate of decline in FVC over 52 weeks was -75.9 ml/year with nintedanib versus -178.6 ml/year with placebo (difference 102.7 ml/year [95% confidence interval 23.2, 182.2]; nominal P = 0.012). No heterogeneity was detected in the effect of nintedanib versus placebo across subgroups based on ILD diagnosis (P = 0.91). The most frequent AE was diarrhea, reported in 63.4% and 27.3% of subjects in the nintedanib and placebo groups, respectively. AEs led to permanent discontinuation of trial drug in 17.1% and 10.2% of subjects in the nintedanib and placebo groups, respectively.In the INBUILD trial, nintedanib slowed the rate of decline in FVC in patients with progressive fibrosing autoimmune disease-related ILDs, with AEs that were manageable for most patients.
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- 2022
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25. Systemic Lupus Erythematosus
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Michelle Petri, Martin Aringer, Isabelle Ayoub, Salem Almaani, Hermine Brunner, Maria Dall’Era, Mengdi Jiang, Richard Furie, Jessica Greco, Fiona Goldblatt, Jennifer Huggins, T. W. J. Huizinga, David Isenberg, Nicholas L. Li, R. C. Monahan, Samir V. Parikh, David Pisetsky, Abin P. Puravath, Brad Rovin, Daniel Wallace, Xuan Zhang, and Lidan Zhao
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- 2023
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26. Moderne medikamentöse Therapie der interstitiellen Lungenerkrankung bei systemischer Sklerose
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Andreas Krause, Udo Schneider, Sven Gläser, Dirk Koschel, and Martin Aringer
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Oncology ,medicine.medical_specialty ,Combination therapy ,business.industry ,Interstitial lung disease ,General Medicine ,medicine.disease ,Mycophenolate ,chemistry.chemical_compound ,Increased risk ,Pharmacotherapy ,chemistry ,Internal medicine ,Medicine ,Nintedanib ,Lung volumes ,Stem cell ,business - Abstract
ZusammenfassungDie systemische Sklerose mit interstitieller Lungenerkrankung (SSc-ILD) ist mit einem erhöhten Morbiditäts- und Mortalitätsrisiko verknüpft. Da es an zugelassenen Medikamenten mangelt, die den Krankheitsverlauf einer SSc-ILD effektiv beeinflussen, besteht ein hoher Bedarf an neuen Therapieoptionen. Die Behandlung mit immunmodulierenden Therapien sowie der autologen Stammzelltransplantation wird in klinischen Studien aktuell weiter untersucht. Kürzlich belegte zudem eine Phase-III-Studie die positive Wirkung des antifibrotischen Wirkstoffs Nintedanib auf den Verlust an Lungenvolumen und somit die Krankheitsprogression bei Patienten mit SSc-ILD. Eine Kombinationstherapie aus Nintedanib und Mycophenolat könnte basierend auf synergistischen Wirkprinzipien zukünftig einen ergänzenden Behandlungsansatz der SSc-ILD darstellen.
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- 2021
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27. Rheumatologie 2021
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Martin Aringer and Stefan Rehart
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ZusammenfassungDie Fortschritte der Rheumatologie haben aus fast regelhaft zu Invalidität und frühem Tod führenden chronischen entzündlich-rheumatischen Erkrankungen gut behandelbare Krankheitsbilder gemacht. Dieser Fortschritt bringt aber auch ein paar Herausforderungen mit sich. Diese CME-Arbeit fasst den aktuellen Stand der Rheumatologie prägnant und anhand der wesentlichen Erkrankungsbilder zusammen und beleuchtet ihre Schnittstellen.
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- 2021
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28. Entwicklung von Qualitätsstandards für die Versorgung von Patient*innen mit rheumatoider Arthritis zur Anwendung in Deutschland
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Silke Zinke, Verena Buschhorn-Milberger, F. Schuch, Uta Kiltz, Klaus Krüger, Martin Aringer, P. Herzer, H.-M. Lorenz, Rotraud Schmale-Grede, S. Späthling-Mestekemper, R. Oltman, Matthias Schneider, H.-J. Lakomek, A. Lauterbach, M. Rudwaleit, J. Braun, Katinka Albrecht, M. I. Hasenbring, Hendrik Schulze-Koops, U. von Hinüber, and Bernhard Manger
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Gynecology ,medicine.medical_specialty ,Rheumatology ,business.industry ,Medicine ,ddc:610 ,Quality of care ,business - Abstract
Despite aqualitatively and structurally good care of patients with rheumatoid arthritis (RA) in Germany, there are still potentially amendable deficits in the quality of care. For this reason, the German Society for Rheumatology (DGRh) has therefore decided to ask agroup of experts including various stakeholders to develop quality standards (QS) for the care of patients with RA in order to improve the quality of care. The QS are used to determine and quantitatively measure the quality of care, subject to relevance and feasibility. The recently published NICE and ASAS standards and asystematic literature search were used as the basis for development. Atotal of 8QS, now published for the first time, were approved with the intention to measure and further optimize the quality of care for patients with RA in Germany. © 2021. The Author(s)., Zusammenfassung Trotz einer qualitativ und strukturell guten Versorgung von Patient*innen mit rheumatoider Arthritis (RA) in Deutschland bestehen weiterhin potenziell behebbare Defizite in der Qualität der Versorgung. Aus diesem Grund hat die Deutsche Gesellschaft für Rheumatologie (DGRh) eine Expert*innengruppe, in der verschiedene Interessengruppen vertreten waren, beauftragt, nationale Qualitätsstandards (QS) mit dem Ziel zu entwickeln, die rheumatologische Versorgung von Patient*innen mit RA in Deutschland qualitativ zu verbessern. QS dienen der Festlegung und quantitativen Messung guter Versorgungsqualität unter dem Vorbehalt von Relevanz und Realisierbarkeit. Als Grundlage für die Entwicklung dienten die kürzlich publizierten Standards von NICE und ASAS und eine systematische Literatursuche. Insgesamt wurden 8 hiermit erstmals veröffentlichte QS konsentiert, die als Grundlage dienen können, die Versorgungsqualität von Patient*innen mit RA in Deutschland zu messen und weiter zu optimieren.
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- 2022
29. Who will respond to type I interferon receptor blockade in SLE?
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Martin Aringer
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Rheumatology ,Immunology ,Immunology and Allergy - Published
- 2022
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30. Glucocorticoid dosing and relapses in giant cell arteritis—a single centre cohort study
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Laura Felten, Nicolai Leuchten, and Martin Aringer
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medicine.medical_specialty ,Prednisolone ,Giant Cell Arteritis ,Single Center ,Gastroenterology ,Cohort Studies ,Rheumatology ,Recurrence ,Internal medicine ,Biopsy ,medicine ,Humans ,Pharmacology (medical) ,Dosing ,Glucocorticoids ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,medicine.disease ,Regimen ,Giant cell arteritis ,Treatment Outcome ,Quartile ,Chronic Disease ,business ,Glucocorticoid ,medicine.drug - Abstract
Objective To investigate the relationship between real life glucocorticoid (GC) dosing and relapse rates in patients with new onset GCA in a single centre. Methods Complete clinical data taken from the inpatient and outpatient records of consecutive GCA patients followed beyond stopping GC were retrospectively analysed for GC doses, other immunomodulatory agents and relapses. Results We included 54 patients with GCA confirmed by biopsy or imaging and followed over their complete GC course. In the 25% dose percentile, patients who needed no pulse therapy at onset reached a dose of 15 mg prednisolone or lower at day 40, of 7.5 mg prednisolone or lower on day 169 (after 24 weeks), and were off prednisolone on day 496 (70 weeks). They were below British Society for Rheumatology recommended doses between week 4 and week 12 and above these after week 14. The cumulative prednisolone dose reached in this 25% quartile was 3.74 g. Of the 54 patients, 24 (44%) relapsed, only four of whom had stopped GC clearly (17–58 weeks) earlier than the 25% dose quartile and one was distinctly (>10%) below the 25% GC percentile. MTX treatment was not significantly associated with fewer relapses (P = 0.178). Conclusion Despite a long-term GC regimen with slow rates of reduction in the low dose range and high cumulative prednisolone doses, 44% of the patients relapsed. Only five (21%) of these relapses may have been prevented by adhering to the recommended GC regimen.
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- 2021
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31. Systemischer Lupus erythematodes durch Tumornekrosefaktor-Blocker – Eine seltene Nebenwirkung einer Uveitis-intermedia-Therapie
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Martin Aringer, Egbert Matthé, Janine Lenk, and Lutz E Pillunat
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Pathology ,medicine.medical_specialty ,Side effect ,business.industry ,Medicine ,Intermediate uveitis ,Tumor necrosis factor alpha ,business ,medicine.disease - Published
- 2021
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32. Neue SLE-Klassifikationskriterien funktionieren bei Kindern
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Martin Aringer
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General Medicine - Abstract
Importance/background: Several diagnostic criteria have been developed to effectively diagnose systemic lupus erythematosus (SLE). Three criteria are most common, namely the American College of Rheumatology (ACR)-1997, the Systemic Lupus International Collaborating Clinics (SLICC)-2012, and the European League Against Rheumatism (EULAR/ACR)-2019. Whether they also apply to juvenile SLE is unclear. Objective: To examine the diagnostic accuracy of ACR-1997, SLICC-2012, and EULAR/ACR-2019 for juvenile SLE. Data sources: A comprehensive search of PubMed, Cochrane, and Embase was conducted up to 26 March 2022. Study selection: We included all study designs in which patients had any index tests for ACR-1997, SLICC-2012, or EULAR/ACR-2019; both full-text papers and conference abstracts published in English were used. Exclusion criteria were as follows: (1) case reports; (2) adult subjects; or (3) did not report sufficient information to acquire true positive, false positive, true negative, and false negative values of diagnostic criteria. Data extraction and synthesis: Two authors independently screened studies, extracted relevant data, and assessed the risk of bias. Main outcomes and measures: First, a meta-analysis of the diagnostic accuracy of EULAR/ACR-2019 and a hierarchical summary receiver operating characteristic (HSROC) model was performed to estimate sensitivity and specificity with 95% confidence intervals (CIs). We then carried out a network meta-analysis to compare the performances of these three diagnostic criteria. Results: In total, 17 relevant studies that included 2339 juvenile SLE patients were eligible to analyze pooled accuracy. In the meta-analysis, 10 studies (1613 cases) reported the diagnostic performance of EULAR/ACR-2019, showing a pooled sensitivity of 0.92 (95% CI, 0.89–0.95), pooled specificity of 0.89 (0.77–0.95), and area under HSROC of 0.96 (0.94–0.97). In the network meta-analysis, the SLICC-2012 (0.94, 0.92–0.96) had the highest sensitivity, followed by EULAR/ACR-2019 (0.93, 0.90–0.95), and ACR-1997 (0.78, 0.72–0.82); the ACR-1997 (0.96, 0.92–0.98) demonstrated the highest specificity. EULAR/ACR-2019 (0.92, 0.87–0.96) and SLICC-2012 (0.92, 0.86–0.96) had the similar specificity. Conclusions and relevance: We found that the applicability of the new EULAR/ACR-2019 criteria in juvenile SLE is not yet the best diagnostic tool. Trial registration: PROSPERO CRD42022321514.
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- 2023
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33. [Anifrolumab in the treatment of systemic lupus erythematosus]
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Martin, Aringer and Sirka, Nitschmann
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Humans ,Lupus Erythematosus, Systemic ,Antibodies, Monoclonal, Humanized - Published
- 2022
34. Polyarthritiden – vom Symptom zur Diagnose
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Martin Aringer and Kristin Wiefel
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Systemic disease ,medicine.medical_specialty ,business.industry ,Arthritis ,General Medicine ,medicine.disease ,Dermatology ,Psoriatic arthritis ,Broad spectrum ,Rheumatoid arthritis ,medicine ,Polyarthritis ,Medical history ,Differential diagnosis ,business - Abstract
Polyarthritis is defined by the palpable synovitic swelling of more than 4 joints. Polyarthritis is always due to a systemic disease and not a local process. Causes include a broad spectrum of rheumatic and infectious diseases with clearly different therapeutic options. It is also important to differentiate arthritis from osteoarthrosis. The objective of this paper is to give an overview on patient history, clinical presentation, diagnostic investigations and the differential diagnosis of the most common diseases that present as polyarthritis.
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- 2021
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35. Systemischer Lupus erythematodes
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Matthias Schneider and Martin Aringer
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Nephrology ,musculoskeletal diseases ,medicine.medical_specialty ,Cyclophosphamide ,Cross-sectional study ,medicine.medical_treatment ,MEDLINE ,Lupus nephritis ,Dermatology ,Disease ,030204 cardiovascular system & hematology ,Patient care ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Pharmacotherapy ,0302 clinical medicine ,Rheumatology ,immune system diseases ,Internal medicine ,Internal Medicine ,medicine ,030212 general & internal medicine ,skin and connective tissue diseases ,Intensive care medicine ,Dialysis ,030203 arthritis & rheumatology ,Gynecology ,Pregnancy ,Accelerated atherosclerosis ,Systemic lupus erythematosus ,Lupus erythematosus ,business.industry ,Autoantibody ,Hydroxychloroquine ,General Medicine ,medicine.disease ,Belimumab ,030220 oncology & carcinogenesis ,Immunology ,Fatal disease ,business ,Nephritis ,Rheumatism ,Anti-SSA/Ro autoantibodies ,medicine.drug - Abstract
Systemic lupus erythematosus (SLE) is a highly variable disease driven by the tendency to form very different types of antibody. This sometimes leads to an exaggerated respect for the complexity of the disease symptoms and to uncertainty in dealing with affected patients; however, nowadays the most important measures in the diagnosis and management of the disease can be broken down to a manageable extent. In this respect, the new recommendations of the European League Against Rheumatism (EULAR) on SLE and the recommendations on lupus nephritis jointly developed by EULAR and the European Renal Association/European Dialysis and Transplant Association (ERA/EDTA) are helpful, as are the new classification criteria from EULAR and the American College of Rheumatology (ACR). In this article the core points of these publications are summarized and contemporary SLE management is presented. As a rule, SLE can be effectively treated when managed in this way.
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- 2021
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36. Effect of Nintedanib on Lung Function in Patients With Systemic Sclerosis−Associated Interstitial Lung Disease: Further Analyses of a Randomized, Double‐Blind, Placebo‐Controlled Trial
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Maher, Toby M., Mayes, Maureen D., Michael, Kreuter, Volkmann, Elizabeth R., Martin, Aringer, Ivan, Castellvi, Cutolo, Maurizio, Christian, Stock, Nils, Schoof, Margarida, Alves, Ganesh, Raghu, and the SENSCIS Trial Investigators
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Adult ,Male ,medicine.medical_specialty ,Vital capacity ,Indoles ,Full Length ,Immunology ,Placebo-controlled study ,Systemic Sclerosis ,Placebo ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,FEV1/FVC ratio ,0302 clinical medicine ,Double-Blind Method ,Rheumatology ,Internal medicine ,Humans ,Immunology and Allergy ,Medicine ,030212 general & internal medicine ,Lung ,Protein Kinase Inhibitors ,Aged ,Scleroderma, Systemic ,business.industry ,Minimal clinically important difference ,Hazard ratio ,Middle Aged ,respiratory system ,Confidence interval ,respiratory tract diseases ,Treatment Outcome ,030228 respiratory system ,chemistry ,Disease Progression ,Female ,Nintedanib ,Lung Diseases, Interstitial ,business ,circulatory and respiratory physiology - Abstract
Objective In the SENSCIS trial in subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) over 52 weeks by 44% versus placebo. This study was undertaken to investigate the effects of nintedanib on categorical changes in FVC and other measures of ILD progression. Methods In post hoc analyses, we assessed the proportions of subjects with categorical changes in FVC % predicted at week 52 and the time to absolute decline in FVC of ≥5% predicted or death and absolute decline in FVC of ≥10% predicted or death. Results A total of 288 subjects received nintedanib and 288 subjects received placebo. At week 52, in subjects treated with nintedanib and placebo, respectively, 55.7% and 66.3% had any decline in FVC % predicted, 13.6% and 20.1% had a decline in FVC of >5% to ≤10% predicted, and 3.5% and 5.2% had a decline in FVC of >10% to ≤15% predicted; 34.5% and 43.8% had a decrease in FVC of ≥3.3% predicted (proposed minimal clinically important difference [MCID] for worsening of FVC), while 23.0% and 14.9% had an increase in FVC of ≥3.0% predicted (proposed MCID for improvement in FVC). Over 52 weeks, the hazard ratio (HR) for an absolute decline in FVC of ≥5% predicted or death with nintedanib versus placebo was 0.83 (95% confidence interval [95% CI] 0.66-1.06) (P = 0.14), and the HR for an absolute decline in FVC of ≥10% predicted was 0.64 (95% CI 0.43-0.95) (P = 0.029). Conclusion These results suggest that nintedanib has a clinically relevant benefit on the progression of SSc-ILD.
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- 2021
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37. Rituximab plus leflunomide in rheumatoid arthritis: a randomized, placebo-controlled, investigator-initiated clinical trial (AMARA study)
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Andrea Rubbert-Roth, Hans-Peter Tony, Harald Burkhardt, Martin Aringer, Klaus Krueger, Ulf Müller-Ladner, T. Rossmanith, Michaela Koehm, Marina Backhaus, Rieke Alten, Eva Herrmann, Annette Lehn, Eugen Feist, Frank Behrens, Siegfried Wassenberg, Herbert Kellner, Gerd R Burmester, and Publica
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rheumatoid arthritis ,Male ,medicine.medical_specialty ,Placebo ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,rituximab ,Rheumatology ,Randomized controlled trial ,law ,Internal medicine ,Clinical endpoint ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Adverse effect ,AcademicSubjects/MED00360 ,investigator-initiated research ,Leflunomide ,Aged ,030203 arthritis & rheumatology ,leflunomide ,business.industry ,Clinical Science ,Middle Aged ,medicine.disease ,randomized clinical trial ,Clinical trial ,Treatment Outcome ,Rheumatoid arthritis ,Antirheumatic Agents ,Rituximab ,Drug Therapy, Combination ,Female ,business ,medicine.drug - Abstract
Objective To investigate the efficacy and safety of rituximab + LEF in patients with RA. Methods In this investigator-initiated, randomized, double-blind, placebo-controlled phase 3 trial, patients with an inadequate response to LEF who had failed one or more DMARD were randomly assigned 2:1 to i.v. rituximab 1000 mg or placebo on day 1 and 15 plus ongoing oral LEF. The primary efficacy outcome was the difference between ≥50% improvement in ACR criteria (ACR50 response) rates at week 24 (P ≤ 0.025). Secondary endpoints included ACR20/70 responses, ACR50 responses at earlier timepoints and adverse event (AE) rates. The planned sample size was not achieved due to events beyond the investigators’ control. Results Between 13 August 2010 and 28 January 2015, 140 patients received rituximab (n = 93) or placebo (n = 47) plus ongoing LEF. Rituximab + LEF resulted in an increase in the ACR50 response rate that was significant at week 16 (32 vs 15%; P = 0.020), but not week 24 (27 vs 15%; P = 0.081), the primary endpoint. Significant differences favouring the rituximab + LEF arm were observed in some secondary endpoints, including ACR20 rates from weeks 12 to 24. The rituximab and placebo arms had similar AE rates (71 vs 70%), but the rituximab arm had a higher rate of serious AEs (SAEs 20 vs 2%), primarily infections and musculoskeletal disorders. Conclusion The primary endpoint was not reached, but rituximab + LEF demonstrated clinical benefits vs LEF in secondary endpoints. Although generally well tolerated, the combination was associated with additional SAEs and requires monitoring. Trial registration EudraCT: 2009-015950-39; ClinicalTrials.gov: NCT01244958.
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- 2021
38. Delayed diagnosis adversely affects outcome in systemic lupus erythematosus: Cross sectional analysis of the LuLa cohort
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Matthias Schneider, Gamal Chehab, Anna Kernder, B. Winkler-Rohlfing, Jutta G Richter, Martin Aringer, Ralph Brinks, and Rebecca Fischer-Betz
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Delayed Diagnosis ,delay ,diagnosis ,Cross-sectional study ,SLE ,Lupus ,Delayed diagnosis ,Severity of Illness Index ,Serology ,Cohort Studies ,Rheumatology ,Germany ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Patient Reported Outcome Measures ,Aged ,Outcome ,Systemic lupus erythematosus ,Systemic lupus ,business.industry ,Middle Aged ,medicine.disease ,Cross-Sectional Studies ,Papers ,Cohort ,Disease Progression ,Quality of Life ,Female ,business - Abstract
Objective Despite increased physician’s awareness and improved diagnostic and serological testing in the recent years, the interval between the initial symptoms and the diagnosis of Systemic lupus erythematosus (SLE) is still very long. Our aim was to study this delay and its association to the outcome of the disease. Methods Information on demographics, onset of first symptoms, first physicians visit and time of diagnosis was assessed by self-reported questionnaires among SLE patients in Germany (LuLa cohort, n = 585) in the year 2012. Disease activity (Systemic Lupus Activity Questionnaire; SLAQ), disease related damage (Brief Index of Lupus Damage; BILD), health related quality of life (Short Form 12) and fatigue (FSS) were chosen as proxies for outcome. Linear regression analysis was used to analyze the association of the delay in diagnosis to the outcome, adjusted for age, disease duration and sex. Results Mean duration between the onset of symptoms and the diagnosis of SLE was 47 months (SD 73). The longer the time to diagnosis, the higher the disease activity (β = 0.199, p Conclusion In systemic lupus erythematosus, longer time to diagnosis was associated with worse outcome. Concepts in care with the intention to shorten the time to diagnosis are needed to improve the long-term outcome of the disease.
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- 2021
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39. Immunpathogenese des systemischen Lupus erythematodes
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Martin Aringer, Stephanie Finzel, and Reinhard E. Voll
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Rheumatology - Abstract
ZusammenfassungDas Verständnis der Immunpathogenese des systemischen Lupus erythematodes (SLE) hilft, das komplexe Krankheitsgeschehen zu verstehen und neue Therapiestrategien zu entwickeln. Die Krankheitsmanifestationen des SLE sind im Wesentlichen Folge von Autoantikörpern, Immunkomplexen und Zytokinen. Insbesondere die Neigung zu unterschiedlichen Autoantikörpern macht das Wesen der Erkrankung aus; die genauen Spezifitäten der Autoantikörper führen zu ganz unterschiedlichen Organmanifestationen. Diese Übersichtsarbeit stellt den klinisch relevanten Stand des Wissens zur SLE-Pathogenese dar – mit dem Ziel, ein für den klinischen Einsatz nützliches Modell zu etablieren, das auch hilft, die neuen Therapieansätze einzuordnen.
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- 2022
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40. [Should HCQ be administered in SLE patients dependent on hemodialysis?]
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Martin, Aringer and Christian, Hugo
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Renal Dialysis ,Antirheumatic Agents ,Humans ,Lupus Erythematosus, Systemic ,Hydroxychloroquine - Published
- 2022
41. [Immunopathogenesis of systemic lupus erythematosus]
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Martin, Aringer, Stephanie, Finzel, and Reinhard E, Voll
- Abstract
Insights into the immunopathogenesis of systemic lupus erythematosus (SLE) help to understand the complex disease patterns and to develop new treatment strategies. The disease manifestations essentially result from autoantibodies, immune complexes and cytokines. Particularly the propensity towards developing various autoantibodies is central to the disease itself; autoantibody specificities lead to highly variable organ manifestations. This review article delineates the clinically relevant state of knowledge on SLE pathogenesis, with the goal to establish a model useful for clinical practice, which also helps to classify the novel therapeutic approaches.Das Verständnis der Immunpathogenese des systemischen Lupus erythematodes (SLE) hilft, das komplexe Krankheitsgeschehen zu verstehen und neue Therapiestrategien zu entwickeln. Die Krankheitsmanifestationen des SLE sind im Wesentlichen Folge von Autoantikörpern, Immunkomplexen und Zytokinen. Insbesondere die Neigung zu unterschiedlichen Autoantikörpern macht das Wesen der Erkrankung aus; die genauen Spezifitäten der Autoantikörper führen zu ganz unterschiedlichen Organmanifestationen. Diese Übersichtsarbeit stellt den klinisch relevanten Stand des Wissens zur SLE-Pathogenese dar – mit dem Ziel, ein für den klinischen Einsatz nützliches Modell zu etablieren, das auch hilft, die neuen Therapieansätze einzuordnen.
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- 2022
42. Evaluation of the European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus in a Population Based Registry
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Allison, Guttmann, Brendan, Denvir, Martin, Aringer, Jill P, Buyon, H Michael, Belmont, Sara, Sahl, Jane E, Salmon, Anca, Askanase, Joan M, Bathon, Laura, Geraldino-Pardilla, Yousaf, Ali, Ellen M, Ginzler, Chaim, Putterman, Caroline, Gordon, Charles G, Helmick, Hilary, Parton, and Peter M, Izmirly
- Abstract
Using the Manhattan Lupus Surveillance Program (MLSP), a multi-racial/ethnic population-based registry, we compared three commonly used classification criteria for Systemic Lupus Erythematosus (SLE) to identify unique cases and determine the incidence and prevalence of SLE using the EULAR/ACR criteria.SLE cases were defined as fulfilling 1997 ACR, SLICC, or EULAR/ACR classification criteria. We quantified the number of cases uniquely associated with each and the number fulfilling all three. Prevalence and incidence using the EULAR/ACR classification criteria and associated 95% confidence intervals (CI) were calculated.1,497 cases fulfilled at least one of the three classification criteria, with 1,008 (67.3%) meeting all three classifications, 138 (9.2%) fulfilling only SLICC criteria, 35 (2.3%) fulfilling only ACR criteria and 34 (2.3%) uniquely fulfilling EULAR/ACR criteria. Patients solely satisfying EULAR/ACR criteria had fewer than four manifestations. The majority classified only by the ACR criteria did not meet any of the defined immunologic criteria. Patients fulfilling only SLICC criteria did so based on the presence of features unique to this system. Using the EULAR/ACR classification criteria, age-adjusted overall prevalence and incidence rates of SLE in Manhattan were 59.6 (95%CI:55.9-63.4) and 4.9 (95%CI 4.3-5.5) per 100,000 population, with age-adjusted prevalence and incidence rates highest among non-Hispanic Black females.Applying the three commonly used classification criteria to a population-based registry identified patients with SLE fulfilling only one validated definition. The most recently developed EULAR/ACR classification criteria revealed similar prevalence and incidence estimates to those previously established for the ACR and SLICC classification schemes.
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- 2022
43. Rheumatologie im Medizinstudium
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Gernot Keyßer, Christoph Baerwald, Melanie Hagen, Martin Feuchtenberger, Raoul Bergner, Martin Aringer, Torsten Witte, H.-M. Lorenz, and C. Gebhardt
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030203 arthritis & rheumatology ,Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,Rheumatology ,business.industry ,medicine ,030212 general & internal medicine ,Bedside teaching ,business - Abstract
Eine solide rheumatologische Grundausbildung im Medizinstudium ist aus 2 Grunden fur die Versorgung rheumatischer Patientinnen und Patienten in der Zukunft essenziell: Einerseits werden zukunftige Hausarztinnen und Hausarzte die Muster entzundlich rheumatischer Erkrankungen beherrschen mussen, um sie rasch genug zu erkennen und die Neuerkrankten rechtzeitig und gezielt in die rheumatologische Versorgung weiterzuleiten. Anderseits ist der weiter bestehende Mangel an Rheumatologinnen und Rheumatologen nur dann perspektivisch zu beheben, wenn es uns gelingt, Interesse fur unser Fach zu wecken. Adaquate rheumatologische Strukturen sind nur in einem Teil der medizinischen Fakultaten Deutschlands vorhanden. Strukturelle Verbesserungen gehen insgesamt nur in kleinen Schritten voran, wurden aber an einigen Standorten erreicht. Je besser die lokalen Strukturen, desto eher ist es auch engagierten rheumatologischen Lehrenden moglich, alle Studierenden der Humanmedizin zu erreichen. Die prufungsrelevanten Lernziele werden vermutlich ab 2026 durch den Nationalen Kompetenz-basierten Lernzielkatalog Medizin (NKLM) vorgegeben werden, der aktuell gemeinsam mit dem Institut fur Medizinische und Pharmazeutische Prufungsfragen (IMPP) in eine Endfassung gebracht wird. Wenn es, wie es derzeit aussieht, gelingt, die systemischen Autoimmunerkrankungen und entzundlich rheumatischen Erkrankungen dort adaquat abzubilden, werden Studierende in Zukunft deutschlandweit besser uber diese Erkrankungen Bescheid wissen und sie schneller erkennen. Daher ist die Arbeit am NKLM von groser Bedeutung. Neben der Arbeit an den Lernzielen bedarf es aber auch deutschlandweit zuganglicher Lernunterlagen auf aktuellem Stand. Diese Lucke sollte das Skriptum schliesen, das die Kommission Studentische Ausbildung der Deutschen Gesellschaft fur Rheumatologie (DGRh) gerade fertiggestellt hat und das nun auf der DGRh-Homepage verfugbar ist.
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- 2020
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44. Classifying and diagnosing systemic lupus erythematosus in the 21st century
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Sindhu R. Johnson and Martin Aringer
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musculoskeletal diseases ,medicine.medical_specialty ,diagnosis ,autoantibodies ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,systemic lupus erythematosus ,Rheumatology ,nephritis ,immune system diseases ,Humans ,Lupus Erythematosus, Systemic ,Medicine ,Pharmacology (medical) ,skin and connective tissue diseases ,Intensive care medicine ,Musculoskeletal System ,AcademicSubjects/MED00360 ,Skin ,030203 arthritis & rheumatology ,Lupus erythematosus ,Disease entity ,business.industry ,medicine.disease ,Lupus Nephritis ,Review article ,classification ,Supplement Papers ,Antibodies, Antinuclear ,business - Abstract
The EULAR/ACR 2019 classification criteria for SLE constitute a current and optimized clinical approach to SLE classification. Classification is still not based on molecular approaches and the results from large studies using polyomics may be interpreted as demonstrating the relevance of the genetic and environmental background rather than splitting SLE into several entities. In fact, an association study within the EULAR/ACR classification criteria project found associations between manifestations only within organ domains. This independency of various organ manifestations argues for SLE as one disease entity. The current review article will therefore concentrate on the clinical and immunological manifestations of SLE and on what we have already learned in this century. Moreover, the structure and essential rules of the EULAR/ACR 2019 classification criteria will be discussed. While classification and diagnosis are distinct concepts, which have to remain clearly separated, information derived from the process towards the classification criteria is also useful for diagnostic purposes. Therefore this article also tries to delineate what classification can teach us for diagnosis, covering a wide variety of SLE manifestations.
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- 2020
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45. Frauen und Gicht – eine diagnostische Herausforderung
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Martin Aringer, Anna Giordano, and Anne-Kathrin Tausche
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Gynecology ,medicine.medical_specialty ,Rheumatology ,business.industry ,Medicine ,business - Abstract
ZusammenfassungHintergrund Von Gicht sind überwiegend Männer betroffen (m:w; 9:1). Zur Diagnosestellung werden daher in der Regel die klinischen Merkmale einer akuten Monarthritis der unteren Extremität beim Mann herangezogen. Im Moment ist die Datenlage zur Gicht bei Frauen begrenzt. Bei ihnen wird die Gicht oft nicht in die Differenzialdiagnosen einer Arthritis einbezogen. Wir untersuchten daher die Epidemiologie und klinische Präsentation der Gicht bei Frauen und verglichen sie mit denen der Gicht bei Männern. In der Folge wurden die Daten auf Merkmale analysiert, welche bei Frauen die Gicht von Arthritiden anderer Genese unterscheiden und damit Fehldiagnosen vermeiden helfen können.Methoden Retrospektiv wurden alle Patienten eingeschlossen, die zwischen 2012 und 2018 mit einer primären Entlassungsdiagnose einer Gicht (ICD-10 M10.XX) am Universitätsklinikum Dresden behandelt wurden. Es wurden klinische, laborchemische sowie radiologische Befunde erfasst und deskriptiv sowie multivariat mittels SPSS und R analysiert. In einem zweiten Schritt wurden die Daten von Frauen mit Gichtarthritis mit denen ohne Gicht (Monarthritis anderer Genese) verglichen und mittels univariater sowie multivariater Regressionsanalyse auf Signifikanz geprüft.Resultate Insgesamt wurden 238 Gicht-Patienten (71 Frauen, 167 Männer) eingeschlossen. Frauen dieser Kohorte waren bei Diagnosestellung im Mittel 20 Jahre älter als Männer und hatten dann insgesamt häufiger mehrere Komorbiditäten: 92% aller Gichtpatientinnen litten an einer Hypertonie (Männer 74%), 84% hatten eine eGFRSchlussfolgerungen Die Gicht muss bei einer akuten Monarthritis auch bei Frauen in die Differenzialdiagnose einbezogen werden. Das gilt besonders ab dem Rentenalter und wenn Hypertonie, kardiovaskuläre Erkrankungen, Diabetes mellitus Typ 2 oder Adipositas vorliegen und Diuretika Teil der Dauermedikation sind. Die Einschränkung der Nierenfunktion und eine Serumharnsäure von>390 µmol/l (>6,5 mg/dL) machen eine Gicht sehr wahrscheinlich.
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- 2020
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46. Leitbild der Rheumatologinnen und Rheumatologen in der Deutschen Gesellschaft für Rheumatologie e. V. (DGRh e. V.)
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Jörg Wendler, Martin Aringer, D. Meyer‑Olson, Philipp Sewerin, Bimba F. Hoyer, Andreas Krause, J. Braun, Ch. Specker, H.-M. Lorenz, Matthias F. Schneider, Johanna Mucke, M. Rudwaleit, Hendrik Schulze-Koops, S. Späthling-Mestekemper, A. Voormann, and Ulf Wagner
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Rheumatology ,business.industry ,Medicine ,business ,Humanities - Published
- 2020
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47. Lupus erkennen und gezielt behandeln
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Martin Aringer
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Nursing ,business.industry ,Medicine ,business ,Pflege Kolleg - Published
- 2020
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48. Biologika und 'small molecules' beim systemischen Lupus erythematodes
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Martin Aringer, Thomas Dörner, and Nicolai Leuchten
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030203 arthritis & rheumatology ,Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,B cell depletion ,Rheumatology ,business.industry ,Medicine ,030212 general & internal medicine ,business - Abstract
Gezielte Therapie ist ein rheumatologischer Traum, der mit den Biologika und zuletzt kleinen Molekulen fur die rheumatoide Arthritis wahr geworden ist – und fur den systemischen Lupus erythematodes (SLE) beginnt, wahr zu werden. Mit Belimumab steht das erste SLE-Biologikum jetzt auch subkutan zur Verfugung. In 4 unabhangigen Studien wurde der Endpunkt erreicht, und die langfristige Belimumab-Therapie hat die Organschadigung verlangsamt, ein zentrales Therapieziel. Die B‑Zell-Depletion mit Antikorpern gegen CD20 bleibt ein relevanter Ansatz, und die Kombination beider Ansatze ist eine spannende Idee. Die Blockade des Typ-I-Interferon-Rezeptors mit Anifrolumab weist eine positive Phase-3-Studie auf und mit Ustekinumab wird die Blockade von Interleukin-12 und -23 in Phase-3-Studien getestet. Auch die alten Ideen der TNF(Tumor-Nekrose-Faktor)- und Interleukin-6-Blockade sind noch nicht vom Tisch. Hinzu kommen die JAK(Januskinase)-Inhibition mit positiven Phase-2-Daten fur Baricitinib und demnachst die Blockade von Bruton-Tyrosinkinase (BTK) sowie die Proteasominhibition. Die SLE-Therapie konnte also demnachst deutlich vielfaltiger werden.
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- 2020
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49. Chemosensory function is decreased in rheumatoid arthritis
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Tran Khan, Thomas Hummel, Jörg Wendler, Ute Walliczek-Dworschak, Antje Hähner, and Martin Aringer
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Olfactory system ,Taste ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Autoantibody ,General Medicine ,Disease ,Olfaction ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Otorhinolaryngology ,Odor ,030220 oncology & carcinogenesis ,Erythrocyte sedimentation rate ,Rheumatoid arthritis ,Internal medicine ,medicine ,030223 otorhinolaryngology ,business - Abstract
Research indicates that rheumatic disorders are accompanied by decreased chemosensory function. The present study aimed to specifically evaluate this issue in patients with rheumatoid arthritis (RA). 212 RA patients (43 men, 169 women, mean age 59 ± 13.3 years), and 30 healthy controls (10 men, 20 women, mean age 40 ± 15.3 years), were included in this study. Chemosensory measurements consisted of olfactory testing using the “Sniffin’ Sticks” test battery (with odor thresholds, odor discrimination and odor identification; OT, OD, OI) and gustatory testing on a suprathreshold and a quasi-threshold level using “taste sprays” and “taste strips”, respectively. In addition, inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) and RA autoantibodies (anti-cyclic citrullinated peptides, RA factors) were evaluated. Olfactory measurements showed 4% of the RA patients functionally anosmic and 40% hyposmic. RA patients scored significantly lower in suprathreshold olfactory tests (OD, OI) compared to controls (OI: 12.5 ± 2.5 vs. 14.1 ± 1.3; OD: 11.3 ± 2.7 vs. 12.9 ± 1.7). In addition, RA patient had decreased taste function compared to healthy individuals (10.4 ± 2.6 vs. 11.7 ± 1.7). Chemosensory function did not correlate with parameters related to the severity of disease. Chemosensory function (taste, OD and OI) appears to be decreased in RA patients. In contrast, OT was not affected. Changes in chemosensory function seem to be independent of disease parameters such as duration of disease or disease activity.
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- 2020
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50. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update
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Josef S Smolen, Robert B M Landewé, Johannes W J Bijlsma, Gerd R Burmester, Maxime Dougados, Andreas Kerschbaumer, Iain B McInnes, Alexandre Sepriano, Ronald F van Vollenhoven, Maarten de Wit, Daniel Aletaha, Martin Aringer, John Askling, Alejandro Balsa, Maarten Boers, Alfons A den Broeder, Maya H Buch, Frank Buttgereit, Roberto Caporali, Mario Humberto Cardiel, Diederik De Cock, Catalin Codreanu, Maurizio Cutolo, Christopher John Edwards, Yvonne van Eijk-Hustings, Paul Emery, Axel Finckh, Laure Gossec, Jacques-Eric Gottenberg, Merete Lund Hetland, Tom W J Huizinga, Marios Koloumas, Zhanguo Li, Xavier Mariette, Ulf Müller-Ladner, Eduardo F Mysler, Jose A P da Silva, Gyula Poór, Janet E Pope, Andrea Rubbert-Roth, Adeline Ruyssen-Witrand, Kenneth G Saag, Anja Strangfeld, Tsutomu Takeuchi, Marieke Voshaar, René Westhovens, Désirée van der Heijde, Rheumatology, AII - Inflammatory diseases, Epidemiology and Data Science, APH - Methodology, Psychology, Health & Technology, Clinical Immunology and Rheumatology, AMS - Ageing & Morbidty, AMS - Amsterdam Movement Sciences, AMS - Musculoskeletal Health, Public Health Sciences, RS: CAPHRI - R2 - Creating Value-Based Health Care, and MUMC+: KIO Kemta (9)
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rheumatoid arthritis ,Synthetic Drugs ,DMARDs (biologic) ,Arthritis, Rheumatoid ,0302 clinical medicine ,RHEUMATOLOGY/EUROPEAN LEAGUE ,Immunology and Allergy ,Biological Products/economics ,030212 general & internal medicine ,INTERLEUKIN-6 RECEPTOR INHIBITION ,skin and connective tissue diseases ,Societies, Medical ,ddc:616 ,treatment ,DOSE GLUCOCORTICOID THERAPY ,economic evaluations ,Antirheumatic Agents/economics/therapeutic use ,Biological Products/economics/therapeutic use ,TREATMENT STRATEGIES ,Europe ,TREAT-TO-TARGET ,Arthritis, Rheumatoid/drug therapy ,Antirheumatic Agents ,Combination ,CONSENSUS-BASED RECOMMENDATIONS ,Drug Therapy, Combination ,DMARDs (synthetic) ,Life Sciences & Biomedicine ,musculoskeletal diseases ,Consensus ,Immunology ,REMISSION INDUCTION ,AMERICAN-COLLEGE ,General Biochemistry, Genetics and Molecular Biology ,Rheumatoid/drug therapy ,Synthetic Drugs/economics ,CERTOLIZUMAB PEGOL ,03 medical and health sciences ,Drug Therapy ,RAPID RADIOGRAPHIC PROGRESSION ,Rheumatology ,Medical ,Synthetic Drugs/economics/therapeutic use ,Humans ,Janus Kinase Inhibitors ,030203 arthritis & rheumatology ,Biological Products ,Science & Technology ,Tumor Necrosis Factor-alpha/antagonists & inhibitors ,Tumor Necrosis Factor-alpha ,Arthritis ,Janus Kinase Inhibitors/therapeutic use ,Antirheumatic Agents/economics ,n/a OA procedure ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Societies ,Systematic Reviews as Topic - Abstract
ObjectivesTo provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field.MethodsAn international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items.ResultsThe task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high.ConclusionsThese updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.
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- 2020
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