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ZusammenfassungDas Antiphospholipidsyndrom (APS) wird klinisch durch venöse oder arterielle Thrombosen sowie Schwangerschaftskomplikationen gekennzeichnet und serologisch durch den Nachweis von Antiphospholipidantikörpern (aPL) bzw. eines Lupusantikoagulans (LA). In den letzten Jahren wurde evident, dass insbesondere bei Vorliegen aller drei serologischen Kriterien, Antikörper gegen Cardiolipin (aCL), gegen ß2-Glykoprotein-1 (aß2-GP1) und ein positives Lupusantikoagulans, die sog. Triple-Positivität, das Risiko für (weitere) thromboembolische und geburtshilfliche Komplikationen deutlich erhöht ist. Therapeutisch werden Thrombozytenaggregationshemmer (ASS), Heparin und Vitamin K Antagonisten eingesetzt. Von der Verwendung direkter oraler Antikoagulantien beim APS wird abgeraten. Eine Immunsuppression ist für die Vermeidung weiterer thromboembolischer Komplikationen eines APS nicht wirksam.

Zusammenfassung Hintergrund In den nächsten Jahren gehen viele Haus- bzw. Fachärzt:innen in den Ruhestand. Wie in anderen Disziplinen stellt sich in der Rheumatologie die Frage, ob ausreichend Weiterbildungsstellen zur Verfügung stehen, um das Versorgungsangebot bedarfsgerecht aufrechterhalten bzw. ausweiten zu können. Daher hat die Deutsche Gesellschaft für Rheumatologie (DGRh) ihre Kommission Fort- und Weiterbildung beauftragt, die aktuell zur Verfügung stehenden Weiterbildungsmöglichkeiten in Deutschland zu überprüfen. Ziel dieser Arbeit ist die Erfassung der Weiterbildungskapazität zur Fachärztin bzw. zum Facharzt für Innere Medizin und Rheumatologie. Methodik Im Rahmen dieser Studie erfolgte die Erhebung der Weiterbildungsbefugten, deren Tätigkeitsort und die Dauer von deren Weiterbildungsbefugnis über die Homepages der 17 Landesärztekammern. Basierend auf diesen Daten erfolgte dann eine deutschlandweite Umfrage zu den Weiterbildungsstellen. Ergebnisse Die Weiterbildung zum/zur Facharzt/Fachärztin für Rheumatologie erfolgte in Deutschland im Jahr 2021 an 229 Weiterbildungsorten. Dabei standen von 187 Weiterbildungsorten nähere Daten für eine Analyse zur Verfügung (81,7 %). Die Weiterbildungsorte verteilten sich dabei auf Kliniken (52,4 %) und Niederlassungen (47,6 %), wobei der Großteil (81,8 %) der insgesamt 478,4 Weiterbildungsstellen (Klinik: 391,4 und Niederlassung: 87) im Krankenhausbereich lag. Insgesamt waren zum Erhebungszeitpunkt 17,2 % aller Weiterbildungsstellen (Klinik: 11,4 % und Niederlassung: 43,1 %) nicht besetzt. Diskussion Die Studie zeigt, dass die meisten Weiterbildungsstellen in klinischen Einrichtungen vorhanden sind. Demgegenüber gibt es im niedergelassenen Bereich vergleichsweise wenige Weiterbildungsstellen, die zudem zur Hälfte nicht besetzt sind. Für eine optimale Nutzung bereits bestehender Weiterbildungskapazitäten müssen sektorübergreifende Weiterbildungskonzepte entwickelt und v. a. muss auch eine eigenständige Vergütung des Weiterbildungsaufwandes etabliert werden. In diesem Kontext muss eine gute rheumatologische Versorgung in ganz Deutschland dauerhaft gewährleistet sein, um den betroffenen ca. 2 Mio. Patienten mit entzündlich rheumatischen Erkrankung gerecht werden zu können.

ZusammenfassungDurch das COVID-19-Register (www.covid19-rheuma.de) der Deutschen Gesellschaft für Rheumatologie erfolgte erstmalig die Erfassung und systematische Evaluation einer viralen Infektion bei Patienten mit entzündlich rheumatischen Erkrankungen (ERE). Hierdurch war und ist eine schnelle Generierung von wissenschaftlichen Daten möglich, welche helfen, die Betreuung von Patienten mit ERE im Rahmen der Pandemie zu verbessern. Neben der Bestätigung allgemeiner Risikofaktoren – auch für Patienten mit ERE – wie Patientenalter und Komorbiditäten (z. B. kardiovaskuläre, chronische Lungen- und Nierenerkrankungen) konnten die Einnahme von Glukokortikoiden und die Krankheitsaktivität der rheumatischen Erkrankung als krankheitsspezifische Risikofaktoren für die Notwendigkeit einer stationären Behandlung wegen COVID-19 identifiziert werden. Auswertungen der kontinuierlich wachsenden Kohorte von Patienten mit entzündlich rheumatischen Erkrankungen und einer COVID-19-Infektion erlauben, Handlungsempfehlungen für die Betreuung der Patienten auf eine bessere Evidenz zu stützen. Die Kooperation mit internationalen rheumatologischen Registern (z. B. europäisches COVID-19-Register für ERE) ermöglicht Analysen aggregierter Kohortendaten von Patienten mit entzündlich rheumatischen Erkrankungen und einer SARS-CoV-2-Infektion für internationale Vergleiche und statistisch noch besser abgesicherte Aussagen.

In the next few years many general practitioners and specialists will retire. As in other disciplines the question arises in rheumatology whether sufficient training positions are available to maintain or expand the supply of care according to demand. Therefore, the German Society of Rheumatology (DGRh) has assigned its committee for education and training to review the currently available training opportunities in Germany. The aim of this work is the quantitative survey of the training capacity to become a specialist in internal medicine and rheumatology.Within the framework of this study, a survey was conducted via the homepages of the 17 state medical associations to determine the postgraduate medical officers, their place of work and the duration of their postgraduate training capabilities. Based on the data, a nationwide survey of training positions was conducted.Specialized rheumatology training is established at 229 training centers in Germany, whereby data from 187 training sites were available for analysis. The training locations are distributed as followed: 52.4% clinical sector and 47.6% outpatient sector. In total, 478.4 training positions are available in Germany (clinical sector: 391.4 and outpatient sector: 87) and 17.2% of the positions (clinical sector: 11.4% and outpatient sector: 43.1%) are not occupied.Based on this study, it can be shown that most of the continuing education positions are available in the clinical sector. In contrast, half of the training positions in the outpatient area are not filled. In order to improve the training situation, it is essential to integrate outpatient colleagues into the training program. This presupposes that further training is supported or financed by the healthcare system. In this context, optimal rheumatological care must be permanently guaranteed throughout Germany in order to provide sufficient care for the approximately 2 million patients with inflammatory rheumatic diseases.HINTERGRUND: In den nächsten Jahren gehen viele Haus- bzw. Fachärzt:innen in den Ruhestand. Wie in anderen Disziplinen stellt sich in der Rheumatologie die Frage, ob ausreichend Weiterbildungsstellen zur Verfügung stehen, um das Versorgungsangebot bedarfsgerecht aufrechterhalten bzw. ausweiten zu können. Daher hat die Deutsche Gesellschaft für Rheumatologie (DGRh) ihre Kommission Fort- und Weiterbildung beauftragt, die aktuell zur Verfügung stehenden Weiterbildungsmöglichkeiten in Deutschland zu überprüfen. Ziel dieser Arbeit ist die Erfassung der Weiterbildungskapazität zur Fachärztin bzw. zum Facharzt für Innere Medizin und Rheumatologie.Im Rahmen dieser Studie erfolgte die Erhebung der Weiterbildungsbefugten, deren Tätigkeitsort und die Dauer von deren Weiterbildungsbefugnis über die Homepages der 17 Landesärztekammern. Basierend auf diesen Daten erfolgte dann eine deutschlandweite Umfrage zu den Weiterbildungsstellen.Die Weiterbildung zum/zur Facharzt/Fachärztin für Rheumatologie erfolgte in Deutschland im Jahr 2021 an 229 Weiterbildungsorten. Dabei standen von 187 Weiterbildungsorten nähere Daten für eine Analyse zur Verfügung (81,7 %). Die Weiterbildungsorte verteilten sich dabei auf Kliniken (52,4 %) und Niederlassungen (47,6 %), wobei der Großteil (81,8 %) der insgesamt 478,4 Weiterbildungsstellen (Klinik: 391,4 und Niederlassung: 87) im Krankenhausbereich lag. Insgesamt waren zum Erhebungszeitpunkt 17,2 % aller Weiterbildungsstellen (Klinik: 11,4 % und Niederlassung: 43,1 %) nicht besetzt.Die Studie zeigt, dass die meisten Weiterbildungsstellen in klinischen Einrichtungen vorhanden sind. Demgegenüber gibt es im niedergelassenen Bereich vergleichsweise wenige Weiterbildungsstellen, die zudem zur Hälfte nicht besetzt sind. Für eine optimale Nutzung bereits bestehender Weiterbildungskapazitäten müssen sektorübergreifende Weiterbildungskonzepte entwickelt und v. a. muss auch eine eigenständige Vergütung des Weiterbildungsaufwandes etabliert werden. In diesem Kontext muss eine gute rheumatologische Versorgung in ganz Deutschland dauerhaft gewährleistet sein, um den betroffenen ca. 2 Mio. Patienten mit entzündlich rheumatischen Erkrankung gerecht werden zu können.

Summary Background Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis. Methods The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5–15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints–erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4–6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov , NCT02573012 . Findings Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35–0·73) with tapered prednisone and −0·08 (–0·27 to 0·12) with continued prednisone (difference 0·61 [0·35–0·88]; p Interpretation In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. Funding F Hoffmann-La Roche.

BackgroundInhibition of interleukin (IL)-1 represents a promising treatment option in adult-onset Still's disease (AOSD).ObjectiveTo investigate the efficacy and safety of canakinumab in patients with AOSD and active joint involvement by means of a multicentre, double-blind, randomised, placebo-controlled trial.MethodsPatients with AOSD and active joint involvement (tender and swollen joint counts of ≥4 each) were treated with canakinumab (4 mg/kg, maximum 300 mg subcutaneous every 4 weeks) or placebo. The primary endpoint was the proportion of patients with a clinically relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28>1.2).ResultsAt enrolment, patients had high active disease with a mean DAS28(ESR) of 5.4 in the canakinumab and 5.3 in the placebo group, respectively. In the intention-to-treat analysis, 12 patients (67%) in the canakinumab group and 7 patients (41%) in the placebo group fulfilled the primary outcome criterion (p=0.18). In the per-protocol analysis, significantly higher American College of Rheumatology (ACR) 30% (61% vs 20%, p=0.033), ACR 50% (50% vs 6.7%, p=0.009) and ACR 70% (28% vs 0%, p=0.049) response rates were observed in the canakinumab group compared with the placebo group. Two patients in the canakinumab group experienced a serious adverse event.ConclusionAlthough the study was terminated prematurely and the primary endpoint was not achieved, treatment with canakinumab led to an improvement of several outcome measures in AOSD. The overall safety findings were consistent with the known profile of canakinumab. Thus, our data support indication for IL-1 inhibition with canakinumab in AOSD.

Cryoglobulinemic vasculitis (CV) is a rare immune complex disease of small vessels (capillaries, venules or arterioles) with detection of cryoglobulins (CG). These are serum proteins that precipitate at temperatures below the normal body temperature. The laboratory diagnostics are logistically challenging because the temperature of the blood sample must be maintained continuously at 37 °C until arrival in the laboratory to prevent early precipitation of the proteins with adsorption to corpuscular blood components. Cryoglobulins can be divided into three classes (types I-III), with each class associated with specific underlying diseases and symptom complexes. Cryoglobulinemia can be caused by hematological, virological or autoimmune diseases and mixed forms also occur. The most common cause to date is a hepatitis C infection. Treatment of the underlying disease is obligatory, with antiviral treatment of hepatitis C offering the rare possibility of causal treatment. Depending on the severity of cryoglobulinemia, immunosuppressive therapy is indicated to prevent permanent damage caused by the inflammation.Die kryoglobulinämische Vaskulitis (KV) ist eine seltene Immunkomplexerkrankung der kleinen Gefäße (Kapillaren, Venolen oder Arteriolen) mit Nachweis von Kryoglobulinen (KG). Hierbei handelt es sich um Serumproteine, die in Temperaturen unterhalb der normalen Körpertemperatur ausfallen. Die Labordiagnostik ist logistisch herausfordernd, da die Temperatur der Blutprobe bis zur Ankunft im Labor bei 37 °C gehalten werden muss, um ein vorzeitiges Ausfallen der Proteine mit Adsorption an den korpuskulären Blutbestandteilen zu verhindern. Kryoglobuline lassen sich in 3 Klassen (Typ I–III) unterteilen, wobei die einzelnen Klassen mit bestimmten Grunderkrankungen und Symptomkomplexen einhergehen. Einer Kryoglobulinämie können sowohl hämatologische, virologische als auch autoimmune Erkrankungen zugrunde liegen, wobei auch Mischformen vorkommen. Die häufigste Ursache ist bislang die Hepatitis-C-Infektion. Eine Therapie der Grunderkrankung ist obligat, wobei die antivirale Therapie der Hepatitis C die seltene Möglichkeit einer kausalen Therapie bietet. Je nach Schwere der Kryoglobulinämie ist eine immunsuppressive Therapie indiziert, um dauerhafte, durch die Entzündung entstandene Schäden zu vermeiden.

IntroductionSeveral risk factors for severe COVID-19 specific for patients with inflammatory rheumatic and musculoskeletal diseases (RMDs) have been identified so far. Evidence regarding the influence of different RMD treatments on outcomes of SARS-CoV-2 infection is still poor.MethodsData from the German COVID-19-RMD registry collected between 30 March 2020 and 9 April 2021 were analysed. Ordinal outcome of COVID-19 severity was defined: (1) not hospitalised, (2) hospitalised/not invasively ventilated and (3) invasively ventilated/deceased. Independent associations between demographic and disease features and outcome of COVID-19 were estimated by multivariable ordinal logistic regression using proportional odds model.Results2274 patients were included. 83 (3.6%) patients died. Age, male sex, cardiovascular disease, hypertension, chronic lung diseases and chronic kidney disease were independently associated with worse outcome of SARS-CoV-2 infection. Compared with rheumatoid arthritis, patients with psoriatic arthritis showed a better outcome. Disease activity and glucocorticoids were associated with worse outcome. Compared with methotrexate (MTX), TNF inhibitors (TNFi) showed a significant association with better outcome of SARS-CoV-2 infection (OR 0.6, 95% CI0.4 to 0.9). Immunosuppressants (mycophenolate mofetil, azathioprine, cyclophosphamide and ciclosporin) (OR 2.2, 95% CI 1.3 to 3.9), Janus kinase inhibitor (JAKi) (OR 1.8, 95% CI 1.1 to 2.7) and rituximab (OR 5.4, 95% CI 3.3 to 8.8) were independently associated with worse outcome.ConclusionGeneral risk factors for severity of COVID-19 play a similar role in patients with RMDs as in the normal population. Influence of disease activity on COVID-19 outcome is of great importance as patients with high disease activity—even without glucocorticoids—have a worse outcome. Patients on TNFi show a better outcome of SARS-CoV-2 infection than patients on MTX. Immunosuppressants, rituximab and JAKi are associated with more severe course.

AimTo determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19.MethodsPeople with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity.ResultsA total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1–5 mg/day 1.86, 1.20 to 2.66, 6–9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab.ConclusionsMore severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.

The current outbreak of the SARS-CoV-2 infection provides countless unprecedented challenges—also with regard to the management of patients with inflammatory rheumatic disease. In an attempt to provide guidance, the German Society of Rheumatology instructed its commission for pharmacotherapy (Kommission Pharmakotherapie) to develop up-to-date recommendations for the management of patients with inflammatory rheumatic diseases during the Covid-19 pandemic. As to date there are little, if any, evidence-based data to scientifically justify guidance, the present preliminary recommendations are based on an expert consensus by 17 experienced rheumatologists in Germany, taking into account analogies to the procedures for other, longer known viral infections, theoretical considerations and already known facts about the SARS-CoV-2 infection. A deviation from these recommendations may be useful in each individual case. The recommendations will be updated frequently (www.dgrh.de). Every physician should also be aware of novel developments while the infection proceeds. 1.1. Patients with inflammatory rheumatic diseases may have an increased risk of infection (box 1). Whether this also applies to SARS-CoV-2 infections is not known. It is also not known whether Covid-19 is more severe in patients with inflammatory rheumatic …

Antiphospholipid syndrome (APS) was first identified in patients with systemic lupus erythematosus (SLE) and frequent occurrence of thromboembolic complications and miscarriages accompanied by detection of anticardiolipin antibodies (aCL). When APS was also later found without an underlying SLE, the so-called primary APS was distinguished from its secondary form with SLE. Even more specific than aCL are the lupus anticoagulant (LA) and antibodies against beta‑2 glycoprotein I (aB2GP I). In recent years, it has become evident that the risk of (further) thromboembolic and obstetric complications is markedly increased if all three serological criteria of APS (aCL, aB2GP I and LA), the so-called triple positivity, are present (high-risk profile). Immunosuppression is not effective in preventing further thromboembolic complications of APS. Low-dose aspirin (LDA), heparin and vitamin K antagonists are used in primary and secondary prophylaxis. The direct oral anticoagulants have an increased risk of complications compared to these treatments and should not be used in cases of high-risk APS.

Recent advances in rheumatology indicate increased relevance of autoantibodies. In this regard, positive ANA are now required as entrance criterium for the first EULAR/ACR classification criteria of SLE. Importantly, ANA diagnostic with detection of isolated anti-dense fine speckled antibodies (DSF-70) need consideration since their unique detection has been identified to exclude largely an autoimmune disease. Thus, highly qualified ANA diagnostic preferably on Hep-2 cell lines is a prerequisite of reliable diagnostics.Recent recommendations for the management of antiphospholipid syndrome define high versus low risk seroprofiles which also guide primary and secondary prophylaxis. Importantly triple positive APS patients (positive for anticradiolipin, anti-s2 GP I positive and carrying lupus anticoagulant) should be treated with vitamin K antagonists while direct oral anticoagulants have been shown to be inferior in terms of risk/benefit. Treatment of obstetric APS is mainly based on low dose aspirin and low molecular heparin. Notably, this treatment should be maintained for 6 weeks after delivery. Thus, serologic findings provide the basis for certain key clinical decisions and require their reliable detection.

The objective is to evaluate the attitude of rheumatologists regarding the use of COVID-19 vaccination in patients with inflammatory rheumatic diseases (IRDs). From February 2nd until March 15th, 2021, rheumatologists from Germany were asked to participate anonymously in a survey addressing their attitude with respect to COVID-19 vaccinations of IRD patients. The survey was completed by 214 participants (107 men, 103 women, 4 unspecified). More than half of the physicians (61%) were working in rheumatologic private practices and 62% had more than 20 years of experience in rheumatology. 90% reported to be at least confidential in handling issues of COVID-19 vaccination and 99% would recommend COVID-19 vaccination for IRD patients. The majority would not recommend to stop or reduce immunomodulatory drugs for vaccination except for rituximab. More than 70% would prefer vaccination with a mRNA vaccine for their IRD patients. This study shows that almost all rheumatologists in Germany support the COVID-19 vaccination for their IRD patients without reducing or terminating the actual immunomodulatory medication to potentially improve the response to the vaccine. This attitude is in accordance with the current recommendations of the German Society of Rheumatology regarding COVID-19 vaccination in IRD patients, and indicates that these have been well accepted and work in everyday clinical practice.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ., Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases. Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

ObjectiveTo investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA).MethodsWe analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders.ResultsOf 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity.ConclusionsPeople with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

To examine the safety and effectiveness of long-term tocilizumab treatment in elderly patients with rheumatoid arthritis (RA) and patients with age-associated comorbidities.ICHIBAN (NCT01194401) was a prospective, non-interventional study that observed adult patients with active moderate-to-severe RA in German rheumatology clinics and practices for up to two years. Patients were to be treated according to the tocilizumab label. Here, we present safety and effectiveness data analysed according to patient age.Of the 3,164 patients treated with at least one dose of tocilizumab, 924 patients were50 years old, 1496 patients were 50-65 years old, and 744 patients were65 years old at baseline. Patients65 years had the highest baseline DAS28-ESR, CDAI, and HAQ-DI scores, along with the highest burden of comorbidities, such as diabetes, coronary heart disease, anaemia, and renal insufficiency. Under treatment with tocilizumab, patients65 years had similar improvements in DAS28-ESR, CDAI and patient-reported outcomes (fatigue, pain, sleeplessness) with similar glucocorticoid savings compared to patient groups65 years. Patients65 years with late-onset RA achieved similar reductions in disease activity compared to early-onset patients. Despite numerically higher rates of adverse events (AEs), serious AEs and serious infections in patients65 years, there were similar rates of AEs leading to withdrawal.Elderly patients in ICHIBAN experienced improvements similar to younger patients in most effectiveness endpoints with only slightly higher rates of AEs, indicating an overall net-positive risk-benefit ratio of tocilizumab treatment regardless of patient age.

ZUSAMMENFASSUNG: Am 21.12.2020 hat die EMA mit der mRNA-Vakzine BNT162b2 der Firmen BioNTech/Pfizer (Comirnaty®, BioNTech, Mainz, Deutschland; Pfizer, New York City, NY, USA) den ersten Impfstoff gegen SARS-CoV‑2 in der Europäischen Union zugelassen, am 06.01.2021 folgte bereits der zweite (Moderna®, Moderna, Cambridge, MA, USA). Viele weitere Zulassungen werden in Kürze folgen. Mit der Verfügbarkeit der Impfung sind bei Patienten/-innen genau wie bei Ärzten/-innen viele Fragen aufgekommen, die in diesem Hot-Topic-Artikel so aktuell wie möglich adressiert werden sollen. ABSTRACT: On 21 December 2020 the European Medicines Agency (EMA) approved the mRNA vaccine BNT162b2 (Comirnaty®, BioNTech, Mainz, Germany; Pfizer, New York City, NY, USA) as the first vaccine against SARS-CoV‑2 in the European Union and the second vaccine (Moderna®, Moderna, Cambridge, MA, USA) followed on 6 January 2021. Many more approvals will follow within a short period of time. With the availability of the vaccination many questions have arisen for patients as well as for physicians, which are addressed as up to date as possible in this hot topic article.

To evaluate risk factors associated with unfavourable outcomes: emergency care, hospitalisation, admission to intensive care unit (ICU), mechanical ventilation and death in patients with immune-mediated rheumatic disease (IMRD) and COVID-19.Analysis of the first 8 weeks of observational multicentre prospective cohort study (ReumaCoV Brasil register). Patients with IMRD and COVID-19 according to the Ministry of Health criteria were classified as eligible for the study.334 participants were enrolled, a majority of them women, with a median age of 45 years; systemic lupus erythematosus (32.9%) was the most frequent IMRD. Emergency care was required in 160 patients, 33.0% were hospitalised, 15.0% were admitted to the ICU and 10.5% underwent mechanical ventilation; 28 patients (8.4%) died. In the multivariate adjustment model for emergency care, diabetes (prevalence ratio, PR 1.38; 95% CI 1.11 to 1.73; p=0.004), kidney disease (PR 1.36; 95% CI 1.05 to 1.77; p=0.020), oral glucocorticoids (GC) (PR 1.49; 95% CI 1.21 to 1.85; p0.001) and pulse therapy with methylprednisolone (PR 1.38; 95% CI 1.14 to 1.67; p=0.001) remained significant; for hospitalisation, age50 years (PR 1.89; 95% CI 1.26 to 2.85; p=0.002), no use of tumour necrosis factor inhibitor (TNFi) (PR 2.51;95% CI 1.16 to 5.45; p=0.004) and methylprednisolone pulse therapy (PR 2.50; 95% CI 1.59 to 3.92; p0.001); for ICU admission, oral GC (PR 2.24; 95% CI 1.36 to 3.71; p0.001) and pulse therapy with methylprednisolone (PR 1.65; 95% CI 1.00 to 2.68; p0.043); the two variables associated with death were pulse therapy with methylprednisolone or cyclophosphamide (PR 2.86; 95% CI 1.59 to 5.14; p0.018).Age50 years and immunosuppression with GC and cyclophosphamide were associated with unfavourable outcomes of COVID-19. Treatment with TNFi may have been protective, perhaps leading to the COVID-19 inflammatory process.

A few days after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was declared a pandemic, the German Society for Rheumatology (DGRh) compiled the first group of recommendations for the care of patients with inflammatory rheumatic diseases in light of SARS-CoV-2/coronavirus disease 2019 (COVID-19). These first recommendations were based on an expert consensus and were largely non-evidence-based. Now that the first scientific data from registries, cross-sectional studies, case reports and case series are available, the DGRh has developed a timely update. This update is based on a literature search of publications available through 15 June 2020 and addresses preventive measures (such as hygiene measures or vaccinations) and the use of immunomodulatory/immunosuppressive drugs. Driven by the commitment to let patients benefit from these new evidence-based recommendations as quickly as possible, the DGRh published the update in German on its homepage and in the Zeitschrift für Rheumatologie immediately after completion. Here we report the key recommendations to make them available to the international community, provide the scientific methodology used to develop the recommendations, give additional thoughts and advice for the management of patients with rheumatic diseases during the COVID-19 pandemic and discuss our recommendations in the context of other international recommendations.

The significance of inflammatory rheumatic diseases (IRDs) and their therapies for the risk of patients with respect to SARS-CoV-2 infection and the course of COVID-19 is still not fully understood. In particular, it is not completely clear whether IRDs, their therapies or other factors in patients with IRDs pose a risk to patients and what consequences should be drawn to protect patients with IRDs. In their manuscript, Nunez et al 1 describe that in a real-world-setting SARS-CoV-2-infected patients with IRDs often require hospitalisation. Important in their observation is that this was associated with systemic autoimmune conditions (as opposed to well-controlled chronic inflammatory arthritis) and related to risk factors known also for the non-rheumatic population, such as advanced age or comorbidities, but not with the immunomodulating, antirheumatic therapy. These data are reassuring, as they underline once again that well-controlled IRDs per se do not pose a risk of contracting SARS-CoV-2 nor do ongoing immunomodulating therapies pose a threat for patients with IRD.2–5 Therefore, in order to avoid reactivation of an underlying IRD and to prevent the risk of increased susceptibility to infection and a possibly necessary administration of glucocorticoids to control immunological activity, several professional societies have advocated in their recommendations for the management of patients with IRDs in times of SARS-CoV-2/COVID-19 the continuation of therapy with anti-inflammatory drugs, provided that clinical symptoms of COVID-19 do not develop.6–8 On the other hand, these guidelines also recommend strict adherence to the hygiene and distance measures to reduce the risk of exposure to the virus. In this respect, several recent comparative surveys of patients with IRDs and the non-rheumatic population have shown that patients with IRDs do not actually have a different risk of infection than the general …

A few days after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was declared a pandemic, the German Society for Rheumatology (DGRh) compiled the first group of recommendations for the care of patients with inflammatory rheumatic diseases in light of SARS-CoV-2/coronavirus disease 2019 (COVID-19). These first recommendations were based on an expert consensus and were largely non-evidence-based. Now that the first scientific data from registries, cross-sectional studies, case reports and case series are available, the DGRh has developed a timely update. This update is based on a literature search of publications available through 15 June 2020 and addresses preventive measures (such as hygiene measures or vaccinations) and the use of immunomodulatory/immunosuppressive drugs. Driven by the commitment to let patients benefit from these new evidence-based recommendations as quickly as possible, the DGRh published the update in German on its homepage and in the Zeitschrift für Rheumatologie immediately after completion. Here we report the key recommendations to make them available to the international community, provide the scientific methodology used to develop the recommendations, give additional thoughts and advice for the management of patients with rheumatic diseases during the COVID-19 pandemic and discuss our recommendations in the context of other international recommendations.

ObjectivesPatients with inflammatory rheumatic diseases (IRD) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be at risk to develop a severe course of COVID-19. The influence of immunomodulating drugs on the course of COVID-19 is unknown. To gather knowledge about SARS-CoV-2 infections in patients with IRD, we established a registry shortly after the beginning of the pandemic in Germany.MethodsUsing an online questionnaire (www.COVID19-rheuma.de), a nationwide database was launched on 30 March 2020, with appropriate ethical and data protection approval to collect data of patients with IRD infected with SARS-CoV-2. In this registry, key clinical and epidemiological parameters—for example, diagnosis of IRD, antirheumatic therapies, comorbidities and course of the infection—are documented.ResultsUntil 25 April 2020, data from 104 patients with IRD infected with SARS-CoV-2 were reported (40 males; 63 females; 1 diverse). Most of them (45%) were diagnosed with rheumatoid arthritis, 59% had one or more comorbidities and 42% were treated with biological disease-modifying antirheumatic drugs. Hospitalisation was reported in 32% of the patients. Two-thirds of the patients already recovered. Unfortunately, 6 patients had a fatal course.ConclusionsIn a short time, a national registry for SARS-CoV2-infected patients with IRD was established. Within 4 weeks, 104 cases were documented. The registry enables to generate data rapidly in this emerging situation and to gain a better understanding of the course of SARS-CoV2-infection in patients with IRD, with a distinct focus on their immunomodulatory therapies. This knowledge is valuable for timely information of physicians and patients with IRD, and shall also serve for the development of guidance for the management of patients with IRD during this pandemic.

With great interest but also some concerns we read the study of Dr Pineda-Sic et al 1 on treatment adherence of patients with inflammatory rheumatic diseases (IRD) during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/COVID-19 pandemic in Latin America. In an anonymous electronic survey of consecutive patients at the rheumatology outpatient clinic of the university hospital in Monterrey, Mexico, the authors requested information about treatment adherence from patients with IRD. From the 345 patients who responded between 14 and 25 May 2020, 293 (85%) had not changed their medication. Importantly, 91.3% of all patients indicated that they knew about the benefits of their treatment. These data are reassuring, as current guidelines, for example by the German Society of Rheumatology (DGRh eV),2 the European League Against Rheumatism3 or the American College of Rheumatology,4 …

We read with interest the study of Fragoulis et al 1 about treatment adherence and behaviour changes of patients with autoimmune inflammatory rheumatic diseases (AIRD) in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/COVID-19 pandemic. In their study, only 11 out of the 500 patients with AIRD interviewed had discontinued antirheumatic treatment solely due to fear of immunosuppression, for example, for fear of an increased risk for SARS-CoV-2 infection. This is reassuring to note as interruption of clinically efficacious therapy in AIRD is associated with an increased risk of relapse2 which might lead to the necessity of intensifying immunosuppressive therapy, possibly beyond the original level. For this very apprehension and also for the accumulating cautious impression that patients with rheumatological diseases might not have a worse prognosis during COVID-19,3 4 …

Antiphospholipid syndrome (APS) was first identified in patients with systemic lupus erythematosus (SLE) and frequent occurrence of thromboembolic complications and miscarriages accompanied by detection of anticardiolipin antibodies (aCL). When APS was also later found without an underlying SLE, the so-called primary APS was distinguished from its secondary form with SLE. Even more specific than aCL are the lupus anticoagulant (LA) and antibodies against beta‑2 glycoprotein I (aB2GP I). In recent years, it has become evident that the risk of (further) thromboembolic and obstetric complications is markedly increased if all three serological criteria of APS (aCL, aB2GP I and LA), the so-called triple positivity, are present (high-risk profile). Immunosuppression is not effective in preventing further thromboembolic complications of APS. Low-dose aspirin (LDA), heparin and vitamin K antagonists are used in primary and secondary prophylaxis. The direct oral anticoagulants have an increased risk of complications compared to these treatments and should not be used in cases of high-risk APS.

Recent advances in rheumatology indicate increased relevance of autoantibodies. In this regard, positive ANA are now required as entrance criterium for the first EULAR/ACR classification criteria of SLE. Importantly, ANA diagnostic with detection of isolated anti-dense fine speckled antibodies (DSF-70) need consideration since their unique detection has been identified to exclude largely an autoimmune disease. Thus, highly qualified ANA diagnostic preferably on Hep-2 cell lines is a prerequisite of reliable diagnostics.Recent recommendations for the management of antiphospholipid syndrome define high versus low risk seroprofiles which also guide primary and secondary prophylaxis. Importantly triple positive APS patients (positive for anticradiolipin, anti-ß2 GP I positive and carrying lupus anticoagulant) should be treated with vitamin K antagonists while direct oral anticoagulants have been shown to be inferior in terms of risk/benefit. Treatment of obstetric APS is mainly based on low dose aspirin and low molecular heparin. Notably, this treatment should be maintained for 6 weeks after delivery. Thus, serologic findings provide the basis for certain key clinical decisions and require their reliable detection.PARADIGMENWECHSEL IN DER KLASSIFIKATION DES SYSTEMISCHEN LUPUS ERYTHEMATODES: Der Nachweis der antinukleären Antikörper oberhalb des Grenzwerts ist Eingangskriterium für die Klassifikation des SLE. Diese Klassifikation beinhaltet 10 unterschiedliche Domänen mit unterschiedlicher Wertigkeit, wobei 10 Punkte für die SLE-Klassifikation erforderlich sind. ANTIPHOSPHOLIPIDSYNDROM: Aktuelle Empfehlungen zum Antiphospholipidsyndrom differenzieren serologisch ein Hochrisiko- (u. a. triple-positiv, Nachweis des Lupus-Antikoagulans) und Niedrigrisiko-Profil (isolierte Anti-Cardiolipin- oder -beta-2-Glykoprotein-I-Antikörper) und begründen damit z. T. Prophylaxe- und Therapieempfehlungen nach arteriellen und venösen Verschlüssen sowie geburtshilflichen APS-Komplikationen.

HINTERGRUND: Muskuloskelettale Symptome und Erkrankungen sind in der Bevölkerung sehr weit verbreitet und verursachen hohe Kosten in Gesundheitswesen und Volkswirtschaft. ZIEL DER ARBEIT: Die Häufigkeit muskuloskelettaler Symptome und Erkrankungen aus den Bereichen Rückenschmerzen, Osteoporose, Arthrose und Arthritis wurde auf Basis von Daten der bevölkerungsbasierten NAKO Gesundheitsstudie beschrieben. MATERIAL UND METHODEN: Die Daten wurden in der ersten Hälfte der NAKO-Basiserhebung von März 2014 bis März 2017 bei Erwachsenen im Alter von 20–75 Jahren erhoben. In die Analysen gingen Daten von 101.779 Interviewteilnehmenden sowie von 9370 Teilnehmenden aus zwei klinischen Untersuchungen ein. Mittels der klinischen Handuntersuchung wurden tastbar geschwollene Gelenke sowie auf Druck schmerzhafte Gelenke identifiziert. Die Winkelstuhluntersuchung lieferte Daten zu Ruheschmerzen am Knie- und Hüftgelenk. Häufigkeiten wurden auf die deutsche Standardbevölkerung 2011 gewichtet. ERGEBNISSE: In den Selbstberichten der Teilnehmenden im Interview wurden am häufigsten jemals diagnostizierte andauernde Rückenschmerzen (22,5 %) und Arthrosen (20,6 %) angegeben, seltener Osteoporose (2,9 %) und rheumatoide Arthritis (1,9 %). In der Handuntersuchung wurden bei 6,0 % Schmerzen an mindestens einem Fingergelenk festgestellt. Laut Winkelstuhluntersuchung waren 8,2 % von einem Ruheschmerz in mindestens einem Knie betroffen sowie 5,1 % an der Hüfte. Frauen berichteten insgesamt häufiger muskuloskelettale Erkrankungen und Symptome als Männer, der Anteil Betroffener nahm mit dem Alter deutlich zu. DISKUSSION: Die Ergebnisse belegen die große Verbreitung vieler muskuloskelettaler Erkrankungen. Die berichtete Beschwerdelast ist mit Ergebnissen aus früheren bevölkerungsbezogenen Erhebungen vergleichbar. BACKGROUND: Musculoskeletal diseases and symptoms are very common in the general population. They lead to high healthcare costs and pose a significant burden to the national economy. OBJECTIVES: Based on data from the population-based German National Cohort (GNC), frequencies of musculoskeletal symptoms and diseases are reported, including back pain, osteoporosis, osteoarthritis, and arthritis. MATERIAL AND METHODS: Data were collected from March 2014 to March 2017 in adults aged 20–75 years during the first half of the baseline survey of the GNC. The sample comprised 101,779 interviewed subjects, including 9370 subjects who underwent clinical musculoskeletal examinations. The interview included questions about specific musculoskeletal disorders. A clinical examination of the hand provided information about palpable swollen joints and pressure-sensitive joints. Resting pain of the knees and hips was also assessed by a clinical examination. Frequencies were standardized to the German standard population of the year 2011. RESULTS: Having ever been diagnosed with recurrent back pain (22.5%) or osteoarthritis (20.6%) were the most common complaints reported in the interview; osteoporosis (2.9%) and rheumatoid arthritis (1.9%) were stated more seldom. According to the hand examination, 6.0% of all participants experienced pain in at least one finger joint. Resting pain was present in at least one knee among 8.2% and in at least one hip among 5.1% of the participants as assessed during the clinical examination. Women were more likely to report musculoskeletal disorders and symptoms than men. The proportion of adults affected by musculoskeletal diseases increased strongly with age. CONCLUSION: Musculoskeletal disorders and symptoms occur frequently. The burden of complaints and diagnoses is comparable to previous population-based surveys.

An imbalanced T-cell homeostasis plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Co-stimulatory and co-inhibitory molecules regulate T-cell differentiation, survival, and cytokine production. B- and T-lymphocyte attenuator (BTLA) is a co-inhibitory molecule which negatively regulates T-cell activation. The aim of this study was to investigate BTLA expression on regulatory and effector CD4+ T-cells in SLE patients with and without lupus nephritis (LN) during active and inactive disease. Therefore, peripheral blood of forty-one SLE patients and twenty-one healthy controls (HC) was phenotypically analyzed. Next, ex vivo stimulated T-cells were analyzed for the expression of BTLA on Th1-, Th2-, and Th17-effector cells by flow cytometry. Renal involvement was defined as biopsy-proven LN. Disease activity was assessed by SLE disease activity index (SLEDAI). Percentages of peripheral unstimulated BTLA+ CD4+ T-cells were significantly decreased in SLE patients with active disease. However, ex vivo stimulated Th1, Th2, and Th17 effector T-cells, expressed increased percentages of BTLA expression in active disease. In contrast, the BTLA expression on CD4+CD25++CD127&minus, regulatory T-cells was not significantly different. BTLA seems to be an important co-inhibitory molecule in the T-cell homeostasis of patients with systemic lupus erythematosus and crucial for disease activity.

Innovations in information and communication technology have been used in rheumatology for many years. In 2018 the German Society for Rheumatology established the Commission "Digital Rheumatology".Mobile data acquisition in rheumatological patients is feasible. It offers innovative possibilities in the implementation of modern treatment strategies. Digital applications such as the "Rheuma Check" and the "Bechterew Check" are available to the public at any time to screen for inflammatory rheumatic diseases. Other digital services and modern networks allow a triage of patients. Rhekiss and RABBIT SpA are the first fully digitalised registries to provide short-term data on issues that are not covered by clinical trials of pharmaceutical companies.Digitalization in Rheumatology will provide much faster answers to important questions in healthcare research in the future.Innovationen in der Informations- und Kommunikationstechnologie haben in der Rheumatologie eine jahrzehntelange Tradition, die Deutsche Gesellschaft für Rheumatologie hat im Jahr 2018 die Kommission „Digitale Rheumatologie“ gegründet.Mobile Datenerfassung rheumatologischer Patienten ist valide möglich. Sie eröffnet damit neuartige Möglichkeiten bei der Umsetzung moderner Behandlungsstrategien. Zum Screening auf entzündlich-rheumatische Systemerkrankungen stehen Interessierten z. B. mit dem „Rheuma-Check“ und dem „Bechterew-Check“ jederzeit digitale Anwendungen zur Verfügung. Die digitalen Angebote sowie moderne Netzwerkstrukturen erlauben eine Triage der Patienten. Mit dem Rhekiss- und dem RABBIT-SpA-Register stehen erstmals vollständig digitalisierte Register zur Verfügung, die kurzfristig Daten zu Fragestellungen liefern, die in klinischen Studien der pharmazeutischen Industrie nicht abgebildet werden.Durch die Digitalisierung in der Rheumatologie können wichtige Fragen der Versorgungsforschung zukünftig deutlich schneller beantwortet werden.