Background
Glucocorticoids are of substantial therapeutic importance in the treatment of inflammatory diseases, but are also associated with bone mineral density loss, osteoporosis, and fractures, ...especially with long-term use.
Objective
To develop recommendations for the management of glucocorticoid-induced osteoporosis (GIOP) in adult patients on long-term glucocorticoid (GC) treatment.
Methods
A systematic literature search (SLR) was conducted to synthesize the evidence for GIOP prevention and treatment options. Recommendations were developed based on SLR/level of evidence and by previously defined questions and in a structured group consensus process.
Results
Recommendations include supplementation with calcium and vitamin D under long-term GC therapy in adults. If specific osteologic treatment is indicated, we recommend bisphosphonates or denosumab as first-line treatment. If fracture risk is high, we recommend teriparatide as primary specific osteologic treatment. Denosumab should be used in cases of severe renal insufficiency, and specific osteologic treatment should not be given in pregnancy. For patients who have not reached the treatment goal, a switch to another class of specific osteologic drugs should be performed. We recommend re-evaluation after a treatment duration of 3–5 years or after termination of long-term GC treatment.
Conclusion
This work aims to provide evidence-based and consensus-based recommendations for the best possible management of GIOP in Germany and to support treatment decisions.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Glucocorticoids are of substantial therapeutic importance in the treatment of inflammatory diseases, but are also associated with bone mineral density loss, osteoporosis, and fractures, especially ...with long-term use.
To develop recommendations for the management of glucocorticoid-induced osteoporosis (GIOP) in adult patients on long-term glucocorticoid (GC) treatment.
A systematic literature search (SLR) was conducted to synthesize the evidence for GIOP prevention and treatment options. Recommendations were developed based on SLR/level of evidence and by previously defined questions and in a structured group consensus process.
Recommendations include supplementation with calcium and vitamin D under long-term GC therapy in adults. If specific osteologic treatment is indicated, we recommend bisphosphonates or denosumab as first-line treatment. If fracture risk is high, we recommend teriparatide as primary specific osteologic treatment. Denosumab should be used in cases of severe renal insufficiency, and specific osteologic treatment should not be given in pregnancy. For patients who have not reached the treatment goal, a switch to another class of specific osteologic drugs should be performed. We recommend re-evaluation after a treatment duration of 3-5 years or after termination of long-term GC treatment.
This work aims to provide evidence-based and consensus-based recommendations for the best possible management of GIOP in Germany and to support treatment decisions.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
EULAR highlighted the essential role of digital health in increasing self-management and improving clinical outcomes in patients with arthritis. The objective of this study was to evaluate the ...efficacy and safety of the digital health application (DHA) in patients with inflammatory arthritis. We assessed demographic parameters, treatment regimen, disease activity, and other patient-reported outcomes at baseline and after 4 weeks of DHA use added to standard care treatment. Of 17 patients, who completed the study, 7 (41.2%) patients were male, ranging from 19 to 63 (40.5 ± 12.2) years. No significant change in antirheumatic treatment was observed during the study. Statistically significant improvements (p < 0.05) were noted for health-related quality of life (increase in Physical Component Summary of Short Form-36 (SF-36) by 23.6%) and disease activity (decrease of Clinical Disease Activity Index and Simple Disease Activity Index by 38.4% and 39.9%, respectively). Clinically significant improvement was demonstrated for SF-36 Total Score (+ 14.4%), disease activity (Rheumatoid Arthritis Disease Activity Index− 5 to 15.9%), and depression (Patient Health Questionnaire− 9 to 13.5%). None of the efficacy parameters showed negative trends. No adverse events were reported throughout the study. The usability level was high i.e., the mean mHealth Application Usability Questionnaire Score of 5.96 (max.: 7.0) demonstrated a high level of application usability. This suggests that using a personalized disease management program based on DHA significantly improves several measures of patient-reported outcomes and disease activity in patients with inflammatory arthritis in a timely manner. These findings highlight the potential of complementary digital therapy in patients with inflammatory arthritis.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Symptom checkers are increasingly used to assess new symptoms and navigate the health care system. The aim of this study was to compare the accuracy of an artificial intelligence (AI)-based symptom ...checker (Ada) and physicians regarding the presence/absence of an inflammatory rheumatic disease (IRD). In this survey study, German-speaking physicians with prior rheumatology working experience were asked to determine IRD presence/absence and suggest diagnoses for 20 different real-world patient vignettes, which included only basic health and symptom-related medical history. IRD detection rate and suggested diagnoses of participants and Ada were compared to the gold standard, the final rheumatologists’ diagnosis, reported on the discharge summary report. A total of 132 vignettes were completed by 33 physicians (mean rheumatology working experience 8.8 (SD 7.1) years). Ada’s diagnostic accuracy (IRD) was significantly higher compared to physicians (70 vs 54%,
p
= 0.002) according to top diagnosis. Ada listed the correct diagnosis more often compared to physicians (54 vs 32%,
p
< 0.001) as top diagnosis as well as among the top 3 diagnoses (59 vs 42%,
p
< 0.001). Work experience was not related to suggesting the correct diagnosis or IRD status. Confined to basic health and symptom-related medical history, the diagnostic accuracy of physicians was lower compared to an AI-based symptom checker. These results highlight the potential of using symptom checkers early during the patient journey and importance of access to complete and sufficient patient information to establish a correct diagnosis.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In atherosclerotic lesions, macrophages are exposed to CSFs and various microenvironmental cues, which ultimately drive their polarization state. We studied the expression of different CSFs in artery ...specimen and cultured vascular cells and assessed whether concurrent stimulation (CS) of monocytes with CSF1 and polarizing cytokines generated macrophages (CSM1 and CSM2) that were phenotypically and functionally different from classically polarized M1 and M2 macrophages. We also assessed the influence of acetylsalicylic acid (ASA) on the capacity of polarized macrophages to stimulate T‐cell proliferation. CSF1 was the most prominent CSF expressed in arteries and cultured vascular cells. M1 and CSM1 macrophages differed in CD86 and CD14 expression, which was up‐regulated respectively down‐regulated by LPS. M2 and CSM2 macrophages were phenotypically similar. Cyclooxygenase expression was different in CSM1 (COX‐1− and COX‐2+ after LPS stimulation) and CSM2 (COX‐1+ and COX‐2−) macrophages. TNFα production was more pronounced in CSM1 macrophages, whereas IL‐10 was produced at higher levels by CSM2 macrophages. Proliferation of allogeneic T cells was strongly supported by CSM2, but not by CSM1 polarized macrophages. Although ASA did not affect anti‐CD3/CD28‐mediated proliferation, it significantly reduced CSM2 and CSM1‐mediated T‐cell proliferation. Supernatants of LPS‐stimulated CSM2 but not of CSM1 macrophages could overcome the inhibition by ASA. Hence, we demonstrate that CSM1 and CSM2 macrophages are phenotypically and to some extent functionally distinct from classically polarized M1 and M2 macrophages. CSM2 macrophages produce a COX‐1‐dependent soluble factor that supports T‐cell proliferation, the identity hereof is still elusive and warrants further studies.
Graphical
Concurrent stimulation of monocytes with CSF1 and IL‐4 generates polarized M2 macrophages that support T‐cell proliferation in a COX‐1 dependent manner upon LPS stimulation.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To analyse the clinical patterns of sarcoidosis triggered by immune checkpoint inhibitors (ICIs) in patients with cancer.
The ImmunoCancer International Registry is a big data–sharing ...multidisciplinary network from 18 countries dedicated to evaluating the clinical research of immune-related adverse events related to cancer immunotherapies.
We identified 32 patients with biopsy-proven sarcoidosis. Underlying cancer included mainly melanoma (n = 24). Cancer immunotherapy consisted of monotherapy in 19 cases (anti-PD-1 in 18 and ipilimumab in 1) or combined ipilimumab + nivolumab in 13. The time median interval between initiation of ICI and sarcoidosis diagnosis was 3 months (range, 2–29 months). The use of combined ICI was associated with a shorter delay in developing sarcoidosis symptoms. The disease was symptomatic in 19 (59%) cases with mostly cutaneous, respiratory and general symptoms. The organs involved included mainly the mediastinal lymph nodes (n = 32), the lungs (n = 11), the skin (n = 10) and the eyes (n = 5). Pulmonary computed tomography studies showed bilateral hilar lymphadenopathy in all cases. There was no severe manifestation. Specific systemic therapy was required in only 12 patients (37%): oral glucocorticoids in 9, and hydroxychloroquine in 3. ICIs were held in 25 patients (78%) and definitively discontinued in 18 (56%) patients. Seven patients continued ICI treatment with a second flare in one case. In six additional patients, an ICI was reintroduced with no harm, and sarcoidosis relapsed in one of them.
Our study shows that ICI-related sarcoidosis seems to have a specific profile, possibly more benign than that of idiopathic sarcoidosis, and does not necessarily imply ICI discontinuation.
•ICI readministration in ICI-related sarcoidosis was not specifically evaluated.•Patients with lung involvement of ICI-related sarcoidosis have a mild presentation.•No patient presented with extrathoracic involvement only.•There was no severe extrathoracic disease.•Stopping ICI in the setting of ICI-induced sarcoidosis is not always necessary.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Prior to surgical interventions physicians and patients with inflammatory rheumatic diseases remain concerned about interrupting or continuing anti-inflammatory medication. For this reason, the ...German Society for Rheumatology has updated its recommendations from 2014.
After a systematic literature search including publications up to 31 August 2021, the recommendations on the use of of glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics (bDMARDs) were revised and recommendations on newer drugs and targeted synthetic (ts)DMARDs were added.
The glucocorticoid dose should be reduced to as low as possible 2-3 months before elective surgery (in any case <10 mg/day) but should be kept stable 1-2 weeks before and on the day of surgery. In many cases csDMARDs can be continued, exceptions being a reduction of high methotrexate doses to ≤15 mg/week and wash-out of leflunomide if there is a high risk of infection. Azathioprine, mycophenolate and ciclosporin should be paused 1-2 days prior to surgery. Under bDMARDs surgery can be scheduled for the end of each treatment interval. For major interventions Janus kinase (JAK) inhibitors should be paused for 3-4 days. Apremilast can be continued. If interruption is necessary, treatment should be restarted as soon as possible for all substances, depending on wound healing.
Whether bDMARDs increase the perioperative risk of infection and the benefits and risks of discontinuation remain unclear based on the currently available evidence. To minimize the risk of a disease relapse under longer treatment pauses, in the updated recommendations the perioperative interruption of bDMARDs was reduced from at least two half-lives to one treatment interval.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Evidence suggests that the anti‐inflammatory nucleoside adenosine can shape immune responses by shifting the regulatory (Treg)/helper (Th17) T‐cell balance in favour of Treg. Since this observation ...is based on in vivo and in vitro studies mostly confined to murine models, we comprehensively analysed effects of adenosine on human T‐cells. Proliferation, phenotype and cytokine production of stimulated T‐cells were assessed by flow cytometry, multiplex assay and ELISA, gene expression profiling was determined by microarray. We found that the pan‐adenosine agonist 5′‐N‐ethylcarboxamidoadenosine (NECA) skews human CD3+ T‐cell responses towards non‐inflammatory Th17 cells. Addition of NECA during T‐cell activation increased the development of IL‐17+ cells with a CD4+ RORγt+ phenotype and enhanced CD161 and CD196 surface expression. Remarkably, these Th17 cells displayed non‐inflammatory cytokine and gene expression profiles including reduced Th1/Th17 transdifferentiation, a stem cell‐like molecular signature and induced surface expression of the adenosine‐producing ectoenzymes CD39 and CD73. Thus, T‐cells cultured under Th17‐inducing conditions together with NECA were capable of suppressing responder T‐cells. Finally, genome‐wide gene expression profiling revealed metabolic quiescence previously associated with non‐pathogenic Th17 cells in response to adenosine signalling. Our data suggest that adenosine induces non‐inflammatory Th17 cells in human T‐cell differentiation, potentially through regulation of metabolic pathways.
Activation of human CD3+ T‐cells in the presence of adenosinergic signalling skewed T‐cell responses towards IL‐17 production and Th17 differentiation. These Th17 cells displayed non‐inflammatory cytokine and gene expression profiles including reduced Th1/Th17 transdifferentiation, a stem cell‐like molecular signature and CD39/CD73 surface expression. T‐cells cultured under Th17‐inducing conditions together with NECA were capable of suppressing responder T‐cells. Finally, genome‐wide expression profiling revealed metabolic quiescence and induction of FOXO signalling pathway as potential underlying changes.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
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.