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Klaus Krueger

Bio: Klaus Krueger is an academic researcher from Praxis. The author has contributed to research in topics: Rheumatoid arthritis & Internal medicine. The author has an hindex of 9, co-authored 28 publications receiving 776 citations.

Papers
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Journal ArticleDOI
TL;DR: Modified-release prednisone is well tolerated, convenient to administer, and produces a clinically relevant reduction of morning stiffness of the joints in addition to all known therapeutic effects of immediate-releaseprednisone.

327 citations

Journal ArticleDOI
TL;DR: Accumulating data suggest that baseline use of bDMARDs is not associated with worse COVID-19 outcome and that some caution may have to be applied when employing rituximab (RTX), a B-cell depleting b DMARD, in patients with immune-mediated disease.
Abstract: It is currently unknown whether immunosuppressive and/or immunomodulating agents such as biological disease-modifying antirheumatic drugs (bDMARDs) affect the rate and the outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections of patients with inflammatory rheumatic diseases (IRDs) While several national authorities have defined patients under immunosuppressive therapy as at risk for severe COVID-19,1 accumulating data from individual cases and also from case series, such as a series from Italy published in the Annals of the Rheumatic Diseases by Monti et al 2 and a report about patients with immune-mediated inflammatory diseases from New York,3 suggest that baseline use of bDMARDs is not associated with worse COVID-19 outcome Although the idea of a potentially protective effect of bDMRADs in COVID-19 is intriguing, we feel that extrapolation of these initial data is dangerous and potentially harmful In particular, some caution may have to be applied when employing rituximab (RTX), a B-cell depleting bDMARD, in patients with immune-mediated disease This notion may be illustrated by the following observations: We recently lost two patients with rheumatoid arthritis (RA) treated with RTX to lethal COVID-19 The first patient, a 71-year-old man with rheumatoid factor positive, …

110 citations

Journal ArticleDOI
TL;DR: Prednisone chronotherapy with the MR tablet was safe and well tolerated and provided a sustained improvement which resulted in a better benefit to risk ratio of low-dose glucocorticoid treatment for at least 12 months.
Abstract: Objective This 9-month open-label extension of the Circadian Administration of Prednisone in Rheumatoid Arthritis Study (CAPRA 1) investigated the long-term safety and efficacy of prednisone chronotherapy with a novel modified-release (MR) prednisone for up to 12 months. Methods Of 288 patients with rheumatoid arthritis originally randomised to MR or immediate-release (IR) prednisone, 249 continued with prednisone chronotherapy (2–10 mg/day) in the 9-month open-label extension. Duration of morning stiffness of the joints (MS), disease activity scores (DAS28), American College of Rheumatology (ACR20) responses and plasma levels of interleukin 6 (IL-6) were assessed. Safety was analysed from adverse event reports and laboratory investigations. Results During the 3-month double-blind phase, patients in the MR group achieved a reduction in MS of 33.1% while no change was observed in the IR group. After 6 months of treatment, MS was reduced in the IR/MR group by 54% and in the MR/MR group by 56%. MS reduction after 12 months was 45% (IR/MR group) and 55% (MR/MR group). Plasma levels of IL-6 declined on MR treatment. DAS28 was reduced from 5.8 to 4.8 (MR/MR group) and 4.9 (IR/MR group), respectively. 37% of the 219 patients who completed the 12-month study achieved improvement according to the ACR20 criteria. Adverse events did not differ from the known profile of low-dose prednisone. Conclusions Prednisone chronotherapy with the MR tablet was safe and well tolerated and provided a sustained improvement which resulted in a better benefit to risk ratio of low-dose glucocorticoid treatment for at least 12 months.

101 citations

Journal ArticleDOI
TL;DR: MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering, and if combined with ACPA testing, allowed prediction of relapse in more than 80% of the patients.
Abstract: Objective To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial. Methods MBDA scores (scale 1–100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse. Results Moderate-to-high MBDA scores were found in 33% of patients with RA overall. Twice as many patients who relapsed (58%) had moderate/high MBDA compared with patients who remained in remission (21%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in patients who were MBDA−/ACPA−, moderate in patients who were MBDA+/ACPA− (33.3%) and MBDA−ACPA+ (31.8%) and high in patients who were MBDA+/ACPA+ (76.4%). Conclusions MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80% of the patients. Trial registration number EudraCT 2009-015740-42.

79 citations

Journal ArticleDOI
TL;DR: In patient populations with low rates of TB incidence and BCG vaccination, the use of both TST and IGRA may maximise sensitivity in detecting LTBI but may also reduce specificity.
Abstract: Objectives To characterise optimal screening strategies for latent tuberculosis infection (LTBI) prior to the initiation of anti-tumour necrosis factor therapy. Methods Patients in 62 German rheumatology centres were evaluated for LTBI. Each patient was screened with a tuberculin skin test (TST) and one form of an interferon-γ release assay (IGRA), either TSPOT.TB (TSPOT) or Quantiferon TB Gold (QFT). Results A total of 1529 patients with rheumatological disease were tested with a TST, 844 with TSPOT and 685 with QFT. TST was positive in 11.3% (n=173). The prevalence of LTBI was 8.0% when defined as a positive TST and no previous Bacille Calmette-Guerin (BCG) vaccination and 7.9% when based on a positive IGRA. Combining both estimates increased the prevalence of LTBI to 11.1%. Clinical risk factors for LTBI were found in 122 patients (34 with a history of prior TB, 81 close contacts and 27 with suggestive chest x-ray lesions). A compound risk factor (CRF) was defined as the presence of at least one of these three risk factors. Statistical analyses were conducted to examine the association between CRF and LTBI test outcomes. In multivariate analysis, TST was influenced by CRF (OR 6.2; CI 4.08 to 9.44, p Conclusion LTBI test results in an individual patient need to be considered in the context of prior BCG vaccination and clinical risk factors. In patient populations with low rates of TB incidence and BCG vaccination, the use of both TST and IGRA may maximise sensitivity in detecting LTBI but may also reduce specificity.

73 citations


Cited by
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Journal ArticleDOI
TL;DR: Twenty-five carefully worded recommendations have been generated based on a critical appraisal of existing guidelines, a systematic review of research evidence and the consensus opinions of an international, multidisciplinary group of experts for the management of hip and knee osteoarthritis.

2,616 citations

Journal ArticleDOI
TL;DR: It becomes apparent that understanding the effects of specific immune interventions can elucidate definitive molecular or cellular nodes that are essential to maintain complex inflammatory networks that subserve diseases like rheumatoid arthritis.

812 citations

Journal ArticleDOI
Cindy Stahn1, Frank Buttgereit1
TL;DR: Improved understanding of mechanisms of glucocorticoid action could enable the development of novel drugs with which to treat patients with inflammatory and autoimmune disease.
Abstract: The strong anti-inflammatory and immunosuppressive effects of glucocorticoids are mediated primarily by the cytosolic glucocorticoid receptors. These receptors are members of the steroid hormone receptor family, a superfamily of ligand-inducible transcription factors, and exert genomic effects that can result in increased expression of regulatory-including anti-inflammatory-proteins (transactivation), or decreased production of proinflammatory proteins (transrepression). Transactivation is thought to be responsible for numerous adverse effects of glucocorticoids; transrepression is thought to be responsible for many of the clinically desirable anti-inflammatory and immunosuppressive effects of glucocorticoids. Optimized glucocorticoids, such as selective glucocorticoid receptor agonists, are being developed to try to minimize the adverse effects many patients experience. Glucocorticoids also exert their effects via rapid, nongenomic mechanisms that can be classified as involving nonspecific interactions of glucocorticoids with cellular membranes, nongenomic effects that are mediated by cytosolic glucocorticoid receptors, or specific interactions with membrane-bound glucocorticoid receptors. Increased understanding of these mechanisms of glucocorticoid action could enable the development of novel drugs with which to treat patients with inflammatory and autoimmune disease.

511 citations

Journal ArticleDOI
TL;DR: The circadian timing system is composed of molecular clocks, which drive 24-h changes in xenobiotic metabolism and detoxification, cell cycle events, DNA repair, apoptosis, and angiogenesis, so that they tick in synchrony in the host tissues that can be damaged by anticancer agents.
Abstract: The circadian timing system is composed of molecular clocks, which drive 24-h changes in xenobiotic metabolism and detoxification, cell cycle events, DNA repair, apoptosis, and angiogenesis. The cellular circadian clocks are coordinated by endogenous physiological rhythms, so that they tick in synchrony in the host tissues that can be damaged by anticancer agents. As a result, circadian timing can modify 2- to 10-fold the tolerability of anticancer medications in experimental models and in cancer patients. Improved efficacy is also seen when drugs are given near their respective times of best tolerability, due to (a) inherently poor circadian entrainment of tumors and (b) persistent circadian entrainment of healthy tissues. Conversely, host clocks are disrupted whenever anticancer drugs are administered at their most toxic time. On the other hand, circadian disruption accelerates experimental and clinical cancer processes. Gender, circadian physiology, clock genes, and cell cycle critically affect outcome on cancer chronotherapeutics. Mathematical and systems biology approaches currently develop and integrate theoretical, experimental, and technological tools in order to further optimize and personalize the circadian administration of cancer treatments.

367 citations

Journal ArticleDOI
TL;DR: Anti-inflammatory cytokines counterbalance the chronic activation of innate and adaptive immune cells in rheumatoid arthritis anducing anti-inflammatory pathways and the resolution of inflammation is an attractive therapeutic option for patients with RA to achieve long-term disease control.
Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a failure of spontaneous resolution of inflammation. Although the pro-inflammatory cytokines and mediators that trigger RA have been the focus of intense investigations, the regulatory and anti-inflammatory cytokines responsible for the suppression and resolution of disease in a context-dependent manner have been less well characterized. However, knowledge of the pathways that control the suppression and resolution of inflammation in RA is clinically relevant and conceptually important for understanding the pathophysiology of the disease and for the development of treatments that enable long-term remission. Cytokine-mediated processes such as the activation of T helper 2 cells by IL-4 and IL-13, the resolution of inflammation by IL-9, IL-5-induced eosinophil expansion, IL-33-mediated macrophage polarization, the production of IL-10 by regulatory B cells and IL-27-mediated suppression of lymphoid follicle formation are all involved in governing the regulation and resolution of inflammation in RA. By better understanding these immune-regulatory signalling pathways, new therapeutic strategies for RA can be envisioned that aim to balance and resolve, rather than suppress, inflammation.

357 citations