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Objectives: The objective of the study was to validate the Ankylosing Spondylitis Disease Activity Score (ASDAS) based on a quick quantitative C-reactive protein (qCRP) assay (ASDAS-Q) in a multicentre, prospective, cross-sectional study in patients with axial spondyloarthritis (axial SpA)., Methods: Disease activity assessment was performed in prospectively recruited patients with axial SpA. Routine laboratory CRP was determined in the central laboratory of each study centre, while quick qCRP and erythrocyte sedimentation rate (ESR) were measured locally. Consequently, ASDAS-CRP, ASDAS-Q using the qCRP and ASDAS-ESR were calculated. The absolute agreement on the disease activity category ascertainment was analysed with cross-tabulations and weighted Cohen's kappa. Bland-Altman plots and intraclass correlation coefficients (ICCs) were used to analyse the criterion validity., Results: Overall, 251 axial SpA patients were included in the analysis. The mean qCRP value (6.34 ± 11.13 mg/l) was higher than that of routine laboratory CRP (5.26 ± 9.35 mg/l). The ICC for routine laboratory CRP versus qCRP was 0.985 [95% confidence interval (CI): 0.972-0.991]. Comparing ASDAS-Q with ASDAS-CRP, 242 of 251 (96.4%) patients were assigned to the same disease activity categories with a weighted Cohen's kappa of 0.966 (95% CI: 0.943-0.988) and ICC of 0.997 (95% CI: 0.994-0.999)., Conclusions: ASDAS-Q showed an almost perfect agreement with ASDAS-CRP in the assignment to specific disease activity categories. Consequently, ASDAS-Q using the qCRP value can be applied as an accurate and quickly available alternative to ASDAS-CRP, thus facilitating the implementation of the treat-to-target concept in clinical trials and clinical routine., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: FP: reports grants and personal fees from Novartis, Lilly and UCB and personal fees from AbbVie, AMGEN, BMS, Hexal, MSD, Pfizer and Roche all outside the presented work. JBJ: reports personal fees from AbbVie, Affibody, BMS, Gilead, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis and UCB all outside the presented work. GRB: reports personal fees from AbbVie, Lilly, Janssen, Novartis, Amgen and Pfizer all outside the presented work. HH: reports personal fees from from Janssen, AbbVie, MSD, Pfizer, Novartis and Roche all outside the presented work. KK: reports personal fees from AbbVie, Lilly, Roche, Novartis, Sanofi and Galapagos all outside the presented work. BM: reports personal fees from UCB, Amgen, Gilead and Hexal Sandoz all outside the presented work. DP: reports grants and personal fees from AbbVie, Eli Lilly, MSD, Novartis and Pfizer, and personal fees from Bristol-Myers Squibb, Roche, UCB, Biocad, GlaxoSmithKline and Gilead all outside the presented work. JS, HCB, HK, SL, MP, VRR, MT, MV and SZ have nothing to disclose., (© The Author(s), 2022.)

This longitudinal analysis compares the prevalence of depressive symptoms in patients with psoriatic arthritis in the context of the COVID-19 pandemic. Data from a national patient register in Germany were analyzed regarding the Patient Health Questionnaire 2 (PHQ-2) to identify cases suspicious for depression at two time points, i.e., before and during the COVID-19 pandemic. Only patients with complete concurrent information on the Disease Activity in Psoriatic Arthritis Score (DAPSA) were included in the analysis. The frequency of depressive symptoms in psoriatic arthritis patients during the COVID-19 pandemic did not differ from the prevalence rates measured before. In addition, prevalence rates for depressive symptoms did not differ when stratifying the patient sample for DAPSA levels of disease activity measured before the pandemic. These results were confirmed further in a sensitivity analysis, limiting the second PHQ-2 assessment to lockdown periods only. However, longitudinal data on the prevalence of depressive symptoms in patients with rheumatic diseases, in general, and psoriatic arthritis, in particular, are scarce in the context of the COVID-19 pandemic. For a sensible comparison of prevalence rates for depressive symptoms in the future, underlying SARS-CoV-2 infection rates and resulting local healthcare disruptions need to be taken into account, besides the potential use of different depression screening tools to evaluate resulting numbers sensibly and draw corresponding conclusions for patient care., Competing Interests: WV, CD, SK, PB-B, CK, KK, SS-M, PA, and MW are members of RheumaDatenRhePort GbR. RHADAR GbR received honoraria from UCB Pharma GmbH, Sandoz Deutschland/Hexal AG, Lilly GmbH, and Galapagos Biopharma Germany GmbH, and research support from Novartis Pharma GmbH. ME received remunerations from RheumaDatenRhePort GbR for statistical data analyses and consultation for previous projects. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Englbrecht, Bartz-Bazzanella, von der Decken, Gauler, Wurth, Aries, Karberg, Kuhn, Schuch, Späthling-Mestekemper, Vorbrüggen, Wendler, Welcker and Kleinert.)

Real-world data are crucial to continuously improve the management of patients with rheumatic and musculoskeletal diseases (RMDs). The German RheumaDatenRhePort (RHADAR) registry encompasses a network of rheumatologists and researchers in Germany providing pseudonymized real-world patient data and allowing timely and continuous improvement in the care of RMD patients. The RHADAR modules allow automated anamnesis and adaptive coordination of appointments regarding individual urgency levels. Further modules focus on the collection and integration of electronic patient-reported outcomes in between consultations. The digital RHADAR modules ultimately allow a patient-centered adaptive approach to integrated medical care starting as early as possible in the disease course. Such a closed-loop system consisting of various modules along the whole patient pathway enables comprehensive and timely patient management in an unprecedented manner., (©Stefan Kleinert, Peter Bartz-Bazzanella, Cay von der Decken, Johannes Knitza, Torsten Witte, Sándor P Fekete, Matthias Konitzny, Alexander Zink, Georg Gauler, Patrick Wurth, Peer Aries, Kirsten Karberg, Christoph Kuhn, Florian Schuch, Susanna Späthling-Mestekemper, Wolfgang Vorbrüggen, Matthias Englbrecht, Martin Welcker, RHADAR Group. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 20.05.2021.)

Even in the era of modern guidelines, the treatment of rheumatic diseases is only as good as the framework of rheumatological care within which the treatment is carried out. The access to high-quality medical treatment for all patients is therefore essentially decisive for the prognosis of the patients. This article describes the current state of outpatient treatment in rheumatology and demonstrates which quality projects, such as treatment contracts, outpatient specialized medical treatment (ASV), digitalization and training as specialized rheumatological assistant (RFA), have been created in order to ensure the treatment of our patients. Furthermore, standards are defined that can guarantee a contemporary and guideline-conform treatment in outpatient rheumatological units. As an example it is an affirmation of the Professional Association of German Rheumatologists (BDRh) for ensuring optimal care for all rheumatology patients through early or emergency rheumatology clinics, treat to target, appropriate delegation of medical duties and diversification of treatment, thus an assurance of the quality and comprehensive treatment in rheumatology. The important topic of safeguarding the next generation of rheumatologists, which is indispensable for this, is also discussed.

Objectives: To capture comorbidity and medication of persons with Sjögren's syndrome (SS) in a population-based cohort in comparison to matched controls., Methods: Individuals with an outpatient diagnosis of M35.0 (ICD-10) in ≥2 quarters of a year or an inpatient diagnosis of M35.0 were identified in a German statutory health insurance fund covering 7.2 million people. Persons in rheumatologic care were grouped by incident or prevalent diagnosis and by co-existing autoimmune disease (sSS) or primary (p)SS and compared to age- and sex-matched controls regarding comorbidity (ICD-10), medical prescriptions, hospitalisation and inability to work in the previous year., Results: In 2018, 7,283 persons (0.10%) had incident and 54,273 persons (0.75%) prevalent SS diagnosis, and 5,961 (11%) were in rheumatologic care. Of these (90% female, mean age 66 years), 3,457 (58%) had further autoimmune disease (sSS), mostly rheumatoid arthritis (80%) and systemic lupus erythematosus (13%). Compared to controls, frequent comorbid conditions in SS were hypertension (controls: 52%, pSS: 55%, sSS: 63%), osteoarthritis (22%/40%/47%), osteoporosis (10%/26%/38%) and depression (21%/34%/36%). Systemic antirheumatic drugs were prescribed in 31% (pSS) and 66% (sSS) while < 5% received topical therapies. Glucocorticoids (8%/34%/59%), NSAIDs (28%/41%/45%), opioids (8%/15%/21%), analgesics (19%/30%/36%) and antidepressants (14%/21%/21%) were frequently prescribed. Compared to controls, hospitalisation (21%/32%/39%) and inability to work in persons <65 years (41%/48%/44%, median days 17/24/30) were more frequent in pSS and sSS than in controls., Conclusions: SS claims diagnosis is associated with substantial comorbidity and frequent prescription of anti-inflammatory drugs, analgesics and antidepressants. The individual and societal burden of SS shows that, in addition to effective treatment strategies, intensive attention to comorbidities is important in this disease.

Background: The vast majority of patients with rheumatoid arthritis (RA) included in the national database of the German Collaborative Arthritis Centers are treated with disease-modifying antirheumatic drugs (DMARD). The clinical and patient-related characteristics of patients who did not have DMARD treatment in the longer term were investigated., Methodology: Between 2012 and 2016 a total of 10,289 patients with RA were documented. Patient characteristics, disease activity and severity, comorbidities and concomitant treatment were descriptively evaluated. Patients who were without DMARDs for more than 1 year and not in remission (disease activity score 28, simple disease activity index or Boolean remission) were analyzed separately. Logistic regression was used to investigate which variables were associated with DMARD treatment., Results: A total of 426 patients were ≤1 year without DMARDs, 1090 > 1 year without DMARDs and 8773 (85%) currently had DMARD treatment. Of the patients who were without DMARDs for more than 1 year, 51% were in remission. Even if no remission criteria were met, the rheumatologists nevertheless found the strived for RA situation in the majority of patients. Of the patients who were without DMARDs for more than 1 year, 13% received glucocorticoid treatment >5 mg/day. In patients with a high degree of severity (odds ratio, OR severe vs. asymptomatic/mild 2.33, 95% confidence interval, CI 1.80;3.02) or positive rheumatoid factor (OR 2.24, CI 1.96;2.56) the chance of receiving DMARD treatment was twice as high. Existing comorbidities did not reduce the chance of receiving DMARD treatment., Conclusion: The RA patients in the national database who had no DMARDs for more than 1 year were mostly in remission or with low disease activity. Signs of inadequate disease control were found in only 11% of all patients without DMARD treatment.

Since April 2018, the new third level care model of outpatient specialist care (ASV) according to §116b of the Social Code Book V (SGBV) has been available for patients with chronic inflammatory rheumatic diseases in Germany. Not only is a multiprofessional cooperation between the disciplines involved in treating rheumatic diseases promoted but also the cooperation between specialized rheumatologists and other specialists in private practice and in hospitals is encouraged. As budget capping limiting services and number of cases do not apply in ASV, a significant improvement of patient care in rheumatology is expected due to an increase in provider capacity. At the end of May 2019, 72 rheumatologists in the first 9 newly approved ASV teams had qualified for this new care concept. Bureaucratic obstacles have so far delayed the implementation of ASV. Difficulties arose in building a team with different specialties, in the process of registration of the teams and the assessment of the registration by certain regional boards responsible for access control. The national associations of rheumatologists, the Professional Association of German Rheumatologists (BDRh), the VRA (Verband der Rheumatologischen Akutkliniken e. V.) and the German Society of Rheumatology (DGRh) campaign for an easier admission of providers to the ASV and for adequate financing of all specialties involved in the ASV. The aim is to realize the chance of the ASV for better rheumatological care nationwide with shorter waiting times for a medical appointment and a better cooperation between specialists.

New treatment strategies and treatment possibilities as well as undertreatment due to the lack of medical specialists especially in rheumatology, necessitate a qualified further training of rheumatological assistant personnel. The increasing independent work of medical and rheumatological assistants expected by physicians with respect to patient management and practice organization, necessitates an intensive cooperation between the two professional groups. The aim is to guarantee the competent treatment of chronically ill patients with rheumatism. Finally, this concept offers the chance of additional professional qualifications for the rheumatological assistant profession and support for rheumatologists in the daily routine. This particularly applies to the engagement at several levels supported by the results of various studies, which indicate tasks that can be delegated to rheumatological assistants and confirm an improvement in the quality of patient care.

Objective: Autoantibodies against CD74 (anti-CD74) are associated with ankylosing spondylitis (AS). The present multicenter study, the International Spondyloarthritis Autoantibody (InterSpA) trial, was undertaken to compare the sensitivity and specificity of anti-CD74 and HLA-B27 in identifying patients with nonradiographic axial spondyloarthritis (axSpA)., Methods: Patients ages 18-45 years with inflammatory back pain of ≤2 years' duration and a clinical suspicion of axSpA were recruited. HLA-B27 genotyping and magnetic resonance imaging of sacroiliac joints were performed in all patients. One hundred forty-nine patients with chronic inflammatory back pain (IBP) not caused by axSpA served as controls, and additional controls included 50 AS patients and 100 blood donors whose specimens were analyzed., Results: One hundred patients with inflammatory back pain received a diagnosis of nonradiographic axSpA from the investigators and fulfilled the Assessment of SpondyloArthritis international Society (ASAS) criteria. The mean age was 29 years, and the mean symptom duration was 12.5 months. The sensitivity of IgA anti-CD74 and IgG anti-CD74 for identifying the 100 axSpA patients was 47% and 17%, respectively. The specificity of both IgA anti-CD74 and IgG anti-CD74 was 95.3%. The sensitivity of HLA-B27 was 81%. The positive likelihood ratios were 10.0 (IgA anti-CD74), 3.6 (IgG anti-CD74), and 8.1 (HLA-B27). Assuming a 5% pretest probability of axSpA in chronic back pain patients, the posttest probability, after consideration of the respective positive test results, was 33.3% for IgA anti-CD74, 15.3% for IgG anti-CD74, and 28.8% for HLA-B27. A combination of IgA anti-CD74 and HLA-B27 results in a posttest probability of 80.2%., Conclusion: IgA anti-CD74 may be a useful tool for identifying axSpA. The diagnostic value of the test in daily practice requires further confirmation., (© 2018, American College of Rheumatology.)

The management of patients with spondyloarthritis (SpA) has experienced a paradigm shift in recent years. This is true for the treatment of axial as well as peripheral manifestations. International treat to target (T2T) recommendations for SpA based on the T2T strategy have now also been published, which contain 5 higher level principles (A-E) in addition to the 15 recommendations. In order to make the recommendations known and to promote national distribution, German experts have now issued a translation of the T2T recommendations for SpA into German.

Objectives: To describe changes in drug treatment and clinical outcomes of ankylosing spondylitis (AS) during the past decade., Methods: The national database of the German collaborative arthritis centres collects clinical and patient-derived data from unselected outpatients with inflammatory rheumatic diseases. Cross-sectional data from 2000 to 2012 of around 1000 patients with AS per year were compared with regard to clinical presentation and quality of life indicators., Results: Non-steroidal anti-inflammatory drugs (NSAIDs) have been the predominant treatment choice in AS over the years with a prescription rate of 67% of patients in 2012. Currently, almost half of the patients with AS in German rheumatology centres are treated with tumour necrosis factor inhibitors (TNFi). Often, both treatments are used in combination (33%), followed by combinations of NSAIDs and synthetic disease modifying antirheumatic drugs (sDMARDs) with 23% or TNFi alone (21%). In 2012, 10% of patients each received NSAID or sDMARD monotherapy. Methotrexate, sulfasalazine, glucocorticoids and analgaesics alone or in combination with other treatments were given to 10% of patients, respectively. Over the years, we have seen remarkable improvements in disease control and patient reported outcomes. These developments are consistent with enhanced functional status, increasing employment rates and decreasing sick leave, hospitalisation and work disability., Conclusions: In the German rheumatology secondary/tertiary care setting, routine care of patients with AS has changed tremendously during the past decade. Increasingly, more efficacious treatment options are reflected in improved clinical outcomes, quality of life and participation in the labour force.

New therapeutic principles and considerable diagnostic advances have made it possible to define different rheumatic diseases and especially rheumatoid arthritis (RA) at an early stage and by starting an early and aggressive medication a considerable proportion of patients with RA will reach the status of low disease activity or even remission. With the additional development of composite measures to estimate the disease activity of RA, it was the goal of an international working group consisting of rheumatologists and patients to develop recommendations for treating rheumatoid arthritis in a similar way as for patients with hypertension or diabetes, with the aim to achieve remission as often as possible. This treat-to-target initiative has taken off in quite a number of different countries including Germany leading to discussions on how this initiative can be integrated into the specific national healthcare systems and what possibilities would exist for its implementation. To develop strategies for an improved healthcare of people suffering from rheumatic diseases and using RA as an example, action elements and postulates were developed which will be discussed in more detail in the present manuscript.

The development of evidence-based treat-to-target (T2T) recommendations alleviates decision-making for the rheumatologist and simultaneously promises substantial improvement of outcome for rheumatoid arthritis (RA) patients. For the office-based rheumatologist in Germany, however, implementation of T2T recommendations contains several difficulties. Limitations arise as a result of an insufficient number of rheumatologists as well as a lack of adequate remuneration both resulting in a lack of time for the individual RA patient. Furthermore budget limitations hinder the appropriate use of antirheumatic drugs and insofar counteract treating to the target of remission. Establishment of selective contracts for rheumatologists by health insurance funds might reduce many of these problems in future for the office-based rheumatologist in Germany.

Background: New strategies and options for the treatment of rheumatoid arthritis (RA) have evolved during the past decade. A study was undertaken to investigate to what extent this influenced daily rheumatological care and how this translates into clinical and patient-reported outcomes., Methods: Data from a total of 38 723 outpatients with RA enrolled in the National Database of the German Collaborative Arthritis Centres in the years 1997-2007 were analysed. The cross-sectional annual data were compared to detect time trends., Results: Between 1997 and 2007 the prescription of combinations of traditional disease-modifying antirheumatic drugs (DMARDs) increased from 8% of all patients to 23%; biological agents were prescribed to 16% of patients with RA in 2007. The mean disease activity (DAS28) fell from 4.5 to 3.4 (median 4.5-3.2). The percentage of patients with low disease activity (DAS28 <3.2) increased significantly from 23% to 49%. The proportion of patients with ≥6 swollen joints fell from 43.1% in 1997 to 8.1% in 2007 and, in those with ≥6 tender joints, from 46.3% to 15.8%. There was a large decrease in the total annual number of days of sick leave due to the rheumatic condition from 27.2 to 8.8 days per gainfully employed person. This reduction is far beyond the decline in the general population. There was also a tendency to higher participation in the work force, specifically in older patients, reflecting the trend seen in the general population., Conclusions: The intensity of drug treatment in patients with RA has increased during the past 7 years. This has been accompanied by not only a decrease in disease activity but also a considerable reduction of economic losses due to sick leave and permanent work disability.

Objective: Autoantibodies against citrullinated peptide antigens (ACPA) are routinely determined to diagnose rheumatoid arthritis (RA) and are predictive of a more severe course of the disease. We here set out to address an involvement of ACPA in the pathogenesis of RA and investigated the recognition pattern of antibodies against 2 citrullinated antigens in more detail., Methods: The sera of 77 patients fulfilling the American College of Rheumatology criteria for RA were analyzed for subclass titers of anti-mutated citrullinated vimentin (MCV) and anticyclic citrullinated peptide (CCP) antibodies by combining subclass specific detection antibodies with commercially available CCP and MCV ELISA plates. Cross-reactivities between anti-MCV and anti-CCP antibodies were detected using a sequential ELISA system., Results: IgG1, IgG3, and IgG4 titers among anti-MCV and anti-CCP antibodies correlated significantly. Cross-reactivity of MCV-specific antibodies against CCP could be detected in 8 of 16 patients' sera; however, cross-binding of MCV-specific IgG4 was weaker compared to total IgG., Conclusion: The inherent capacity of IgG4 to exchange F(ab) arms provides insight into the anti-MCV antibody diversity and suggests a classification of ACPA positive patients into broad and narrow responders.

Objective: Antibody subclasses reflect specific immunological processes and may be indicative of the underlying pathological pattern in an autoimmune disease like RA. We therefore quantified anti-cyclic citrullinated peptides (CCP) and anti- citrullinated vimentin (MCV) IgG subclass titres in RA patients and compared them with the respective titres of antibodies directed against the varicella zoster virus (VZV) and to total serum titres., Methods: Sera of 77 patients fulfilling the ACR criteria for RA were collected. An IgG subclass-specific ELISA system was then established and combined with commercially available MCV, CCP and VZV pre-coated microtitre plates., Results: Even though IgG1 is the predominant subclass among antibodies against CCP and MCV in RA patients, IgG4 is second with respect to titres and frequencies. This increase in IgG4 among RA-specific antibodies is independent of disease duration and does not reflect a general skewing of the immune response in these patients as overall serum titres and antibodies directed against VZV show a normal distribution of IgG1, IgG2, IgG3 and IgG4., Conclusion: Elevated IgG4 titres are specific for auto-antibodies against citrullinated antigens in RA and are indicative of a Th2-biased environment during the generation of auto-reactive plasma cells. We discuss here an indirect role for IgG4 auto-antibodies in hindering the elimination of auto-reactive B and plasma cells and thus driving the autoimmune process.

Objective: To define the relationship between bone growth (syndesmophytes) and bone loss (osteoporosis) in ankylosing spondylitis (AS)., Methods: Bone mineral density (BMD) at the spine, hip, and radius was measured by dual-energy x-ray absorptiometry (DEXA), dual-energy quantitative computed tomography (DEQCT), and peripheral quantitative computed tomography (pQCT) in 103 patients with AS. Radiographs of the lumbar spine were used to detect syndesmophytes. Patients were divided in 3 groups according to disease duration., Results: Osteopenia at the hip and spine was found by DEXA in 56% and 41%, respectively, of the patients with disease duration < 5 years (n = 27), with an additional 11% and 15% having osteoporosis. In patients with a longer disease duration, > 10 years (n = 28), 29% were osteoporotic at the hip and only 4% at the lumbar spine. In contrast, using spinal DEQCT, 59% of patients with early disease were found to be osteopenic; 36% of patients with long-standing disease were osteopenic and 18% were osteoporotic. More than half the patients (55%) had syndesmophytes (n = 55). With spinal DEQCT there were more patients with syndesmophytes (63%) in the group with reduced bone density than in the group without (45%). This was similar with DEXA measurements at the hip, where 31% compared to 14% had osteoporosis, respectively. Osteocalcin was elevated in 34% of patients, but was not associated with disease activity or BMD., Conclusion: The majority of patients with AS had reduced bone density. The method of bone density measurement is critical and should be different depending on disease duration. The finding that more patients with syndesmophytes had reduced bone density than those without suggests that bone growth and bone loss occur in parallel, and the role of inflammation in this process warrants further investigation.

Symptomatic manubriosternal arthritis, occasionally encountered with spondyloarthropathies, may not be adequately controlled by systemic therapy. Local corticosteroid injections make a potential contribution to symptomatic management. Three patients with acute inflammation of the joint as documented by MRI and fluoroscopy-guided therapy are presented. Topical treatment with triamcinolone acetonide (40 mg) was well tolerated and induced rapid and complete relief of pain for between 3 weeks and 3 months. In spite of the clinical improvement, the signs of inflammation in MRI did not decrease. Local steroid application seems to be an underused therapeutic modality in managing rheumatic involvement of the anterior chest wall.