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Frank Buttgereit

Bio: Frank Buttgereit is an academic researcher from Charité. The author has contributed to research in topics: Rheumatoid arthritis & Medicine. The author has an hindex of 66, co-authored 392 publications receiving 19854 citations. Previous affiliations of Frank Buttgereit include Leibniz Association & Humboldt State University.


Papers
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Journal ArticleDOI
TL;DR: These recommendations intend informing rheumatologists, patients, national rheumology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.
Abstract: In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at

4,730 citations

Journal ArticleDOI
TL;DR: The recommendations for the management of LVV have been updated to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.
Abstract: BACKGROUND Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. METHODS Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations. RESULTS Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons. CONCLUSIONS We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.

564 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
01 Mar 2003-Immunity
TL;DR: The macroEconomics of protein synthesis and degradation and the microeconomics of producing MHC class I associated peptides from viral translation products are quantitated and the efficiency of complex formation is similar in dendritic cells and macrophages, which play a critical role in activating T cells in vivo.

502 citations

Journal ArticleDOI
TL;DR: Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo.
Abstract: Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose glucocorticoid treatment show that few of the commonly held beliefs about their incidence, prevalence, and impact are supported by clear scientific evidence. Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo.

472 citations


Cited by
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Journal ArticleDOI
TL;DR: These recommendations intend informing rheumatologists, patients, national rheumology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.
Abstract: In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at

4,730 citations

01 Jan 2011
TL;DR: Recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA based on evidence and expert opinion.
Abstract: Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-à-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.

3,485 citations

Journal ArticleDOI
TL;DR: The wide range of immune-related adverse effects associated with immune checkpoint blockade can complicate this effective therapy and limit its use in patients with cancer.
Abstract: Side Effects of Immune Checkpoint Blockade The wide range of immune-related adverse effects associated with immune checkpoint blockade can complicate this effective therapy and limit its use in patients with cancer. This review surveys the adverse effects and their management.

2,658 citations

Journal ArticleDOI
TL;DR: To develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA), a large number of patients with RA are referred to a single clinic for treatment with these medications.
Abstract: Objective To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). Methods We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. Results The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. Conclusion This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

2,083 citations