Publications by authors named "Stefan Kleinert"

Objectives: Although patients with immune-mediated inflammatory diseases (IMID) are thought to be more susceptible to viral infections, it is unclear whether their presentation differs between patients with IMID and healthy controls. This study aimed to investigate the symptom pattern of common viral infections in patients with IMID and compare it with controls without IMIDs.

Design: A cross-sectional study conducted between 1 February and 30 April 2020, using a questionnaire.

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Background: Safety recommendations for Janus kinase inhibitors (JAKi) issued by the European Medical Agency (EMA) in 2023 could potentially influence treatment patterns for rheumatoid arthritis (RA) drugs, but little is known about the impact of these recommendations in routine clinical care.

Methods: We retrospectively analyzed the German RHADAR rheumatology database for adult patients with RA and documentation of a new therapy with a JAKi, tumor necrosis factor inhibitor (TNFi), or interleukin-6 receptor inhibitor (IL-6Ri). Data were grouped into half-yearly intervals from quarter (Q)2/2020 to Q3/2023.

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  • Janus kinase inhibitors (JAKi) have recently been approved alongside tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) as treatment options for axial spondyloarthritis (axSpA), yet their real-world drug survival is under-studied.
  • A retrospective analysis of 1,222 axSpA patients, focusing on treatment initiation timing from January 2015 to October 2023, reveals median drug survival rates of 31 months for TNFi, 25 months for IL-17i, and 18 months for JAKi.
  • Higher discontinuation rates were seen for JAKi and IL-17i compared to TNFi, with
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  • The study investigates the diagnostic accuracy of two digital tools, an AI-based symptom checker (Ada) and a web-based self-referral tool (Rheport), for identifying inflammatory rheumatic diseases (IRDs) among patients at three rheumatology centers.
  • A total of 600 patients participated, with results showing that Rheport and Ada had varying levels of success in correctly identifying IRDs, achieving diagnostic accuracies of 52% and 58% respectively.
  • The tools notably had better performance in diagnosing rheumatoid arthritis compared to other IRDs, with Ada showing a higher sensitivity for this specific condition.
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  • Treatment options for psoriatic arthritis have expanded to include various biologic DMARDs and Janus kinase inhibitors, but real-world data on their persistence in patients is limited.
  • A study analyzed 1352 prescriptions and found that the 5-year survival rates were highest for IL-17 inhibitors (67.8%) and lowest for IL-12/23 inhibitors (46.0%), with JAKi showing a higher likelihood of discontinuation.
  • The findings suggest that patients in Germany may stick with TNFi and IL-17i longer than IL-12/23i or JAKi, potentially influenced by disease severity and other health conditions like osteoarthritis.
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Background: Individuals with anti-citrullinated protein antibodies (ACPAs) and subclinical inflammatory changes in joints are at high risk of developing rheumatoid arthritis. Treatment strategies to intercept this pre-stage clinical disease remain to be developed. We aimed to assess whether 6-month treatment with abatacept improves inflammation in preclinical rheumatoid arthritis.

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  • The study explored the differentiation between radiographic (r-axSpA) and non-radiographic (nr-axSpA) axial spondyloarthritis in a real-world clinical setting, analyzing data from 371 patients in Germany.
  • Findings showed that nearly half of the patients were classified as having definite r-axSpA, with those in this category receiving more aggressive treatment options like disease-modifying antirheumatic drugs (DMARDs) compared to nr-axSpA patients.
  • The availability of radiographic imaging was limited, with only about 58% of patients having the necessary imaging documentation, and follow-up imaging was rare; however, it confirmed r-axSpA in approximately 40
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Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, we analyzed the impact of tapering or stopping DMARD treatment on the physical function of RA patients.

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  • Axial spondyloarthritis (axSpA) is often not diagnosed on time, leading to significant impacts on patients' lives; the study aims to understand public interest and unmet needs by analyzing web search data in Germany.* -
  • Over a four-year period, 265 axSpA-related keywords were identified with close to 3.9 million total searches; most queries focused on definitions rather than symptoms or management.* -
  • The data showed that smaller cities had higher search volumes per capita, and there were consistent search trends with a notable peak in July 2017, suggesting that these insights can help shape public health efforts and improve axSpA care.*
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  • * Patients with axSpA displayed greater impairments in selective attention compared to matched healthy individuals, while the PsA group showed better episodic short-term memory performance.
  • * Further research is needed to explore factors influencing cognitive changes; the current study suggests that impairments in selective attention could affect information processing in these patients.
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  • A study was conducted to compare the accuracy of an AI symptom checker (Ada) with physicians in diagnosing inflammatory rheumatic diseases (IRD) using real-world patient scenarios.
  • * The study involved 33 experienced German-speaking rheumatologists who evaluated 20 patient vignettes, and Ada outperformed the physicians in identifying IRD, with accuracy rates of 70% compared to 54%.
  • * Findings suggest that AI tools like Ada could effectively aid in early diagnosis and emphasize the need for comprehensive patient information to improve diagnostic accuracy.*
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  • Concerns about the effectiveness of SARS-CoV-2 vaccines in patients with immune-mediated inflammatory diseases prompted a study to examine their vaccine responses and the impact of factors like treatment and vaccination schedules.
  • The study tracked the SARS-CoV-2 IgG antibody responses of over 5,000 participants, including healthy individuals and those with immune-mediated diseases, using a questionnaire and specialized lab tests over a specific timeframe.
  • Findings indicated that healthy controls had significantly higher antibody levels than patients with immune-mediated inflammatory diseases throughout the study period, highlighting potential vulnerabilities in the latter group regarding vaccine effectiveness.
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  • Rheport is an online system designed for rheumatology that triages patient referrals to assess the likelihood of inflammatory rheumatic diseases (IRD), but its current accuracy is limited.
  • A study tested nine machine learning models using a dataset from a national rheumatology registry to improve this accuracy, with results showing that ML models significantly outperformed the existing algorithm.
  • Key factors influencing IRD classification were identified, including finger joint pain and inflammatory markers, suggesting that enhancing the system with more lab data could further improve its performance.
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Objective: To investigate the impact of biologic disease-modifying antirheumatic drug (bDMARD) treatment on the prevalence, seroconversion rate, and longevity of the humoral immune response against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs).

Methods: Anti-SARS-CoV-2 IgG antibodies were measured in a prospective cohort of health care professional controls and non-health care controls and IMID patients receiving no treatment or receiving treatment with conventional or biologic DMARDs during the first and second COVID-19 waves. Regression models adjusting for age, sex, sampling time, and exposure risk behavior were used to calculate relative risks (RRs) of seropositivity.

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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.

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Background: Owing to increasing remission rates, the management of patients with rheumatoid arthritis in sustained remission is of growing interest. The Rheumatoid Arthritis in Ongoing Remission (RETRO) study investigated tapering and withdrawal of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis in stable remission to test whether remission could be retained without the need to take DMARD therapy despite an absence of symptoms.

Methods: RETRO was an investigator-initiated, multicentre, prospective, randomised, controlled, open-label, parallel-group phase 3 trial in patients aged at least 18 years with rheumatoid arthritis for at least 12 months before randomisation who were in sustained Disease Activity Score using 28 joints with erythrocyte sedimentation rate (ESR) remission (score <2·6 units).

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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.

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  • The study aims to investigate how immune-mediated inflammatory diseases (IMIDs) affect the body's response to SARS-CoV-2 vaccines.
  • In a comparison of vaccinated patients with IMIDs and healthy controls, it was found that while most controls developed antibodies, about 6% of patients did not, and those with IMIDs had lower neutralizing antibody levels.
  • The results suggest that the reduced immune response in patients with IMIDs is primarily due to the disease itself, not the treatments they are receiving.
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Background: Timely diagnosis and treatment are essential in the effective management of inflammatory rheumatic diseases (IRDs). Symptom checkers (SCs) promise to accelerate diagnosis, reduce misdiagnoses, and guide patients more effectively through the health care system. Although SCs are increasingly used, there exists little supporting evidence.

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Immune-mediated inflammatory diseases (IMIDs) of the joints, gut and skin are treated with inhibitors of inflammatory cytokines. These cytokines are involved in the pathogenesis of coronavirus disease 2019 (COVID-19). Investigating anti-SARS-CoV-2 antibody responses in IMIDs we observe a reduced incidence of SARS-CoV-2 seroconversion in IMID patients treated with cytokine inhibitors compared to patients receiving no such inhibitors and two healthy control populations, despite similar social exposure.

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Objectives: To 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.

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Objective: To analyze the effect of a risk-stratified disease-modifying antirheumatic drug (DMARD)-tapering algorithm based on multibiomarker disease activity (MBDA) score and anticitrullinated protein antibodies (ACPA) on direct treatment costs for patients with rheumatoid arthritis (RA) in sustained remission.

Methods: The study was a posthoc retrospective analysis of direct treatment costs for 146 patients with RA in sustained remission tapering and stopping DMARD treatment, in the prospective randomized RETRO study. MBDA scores and ACPA status were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3).

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Objective: Up to one-third of patients with T cell large granular lymphocyte (T-LGL) leukemia display symptoms of rheumatoid arthritis (RA). In Crohn's disease and psoriasis, treatment with tumor necrosis factor (TNF) inhibitors is associated with hepatosplenic γδ T cell lymphoma and with clonal expansion of γδ T cells, respectively. This study was undertaken to determine the prevalence of clonal T-LGL cells in patients with RA and define risk factors for this rare hematologic malignancy.

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Objective: To validate standard self-report questionnaires for depression screening in patients with rheumatoid arthritis (RA) and compare these measures to one another and to the Montgomery-Åsberg Depression Rating Scale (MADRS), a standardized structured interview.

Methods: In 9 clinical centers across Germany, depressive symptomatology was assessed in 262 adult RA patients at baseline (T0) and at 12 ± 2 weeks followup (T1) using the World Health Organization 5-Item Well-Being Index (WHO-5), the Patient Health Questionnaire (PHQ-9), and the Beck Depression Inventory II (BDI-II). The construct validity of these depression questionnaires (using convergent and discriminant validity) was evaluated using Spearman's correlations at both time points.

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Objective: To perform a detailed analysis of the autoantibody response against post-translationally modified proteins in patients with rheumatoid arthritis (RA) in sustained remission and to explore whether its composition influences the risk for disease relapse when tapering disease modifying antirheumatic drug (DMARD) therapy.

Methods: Immune responses against 10 citrullinated, homocitrullinated/carbamylated and acetylated peptides, as well as unmodified vimentin (control) and cyclic citrullinated peptide 2 (CCP2) were tested in baseline serum samples from 94 patients of the RETRO study. Patients were classified according to the number of autoantibody reactivities (0-1/10, 2-5/10 and >5/10) or specificity groups (citrullination, carbamylation and acetylation; 0-3) and tested for their risk to develop relapses after DMARD tapering.

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