Genetically proxied IL-1 receptor antagonism and risk of polymyalgia rheumatica.
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ABSTRACT:
SUBMITTER: Zhao SS
PROVIDER: S-EPMC10836967 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
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Genetically proxied IL-1 receptor antagonism and risk of polymyalgia rheumatica.
Zhao Sizheng Steven SS Rajeswaran Thurkka T Mackie Sarah L SL Yarmolinsky James J
Rheumatology (Oxford, England) 20240201 2
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Project description:BackgroundPolymyalgia rheumatica is one of the most common inflammatory rheumatologic conditions in older adults. Other inflammatory rheumatologic disorders are associated with an excess risk of vascular disease. We investigated whether polymyalgia rheumatica is associated with an increased risk of vascular events.MethodsWe used the General Practice Research Database to identify patients with a diagnosis of incident polymyalgia rheumatica between Jan. 1, 1987, and Dec. 31, 1999. Patients were matched by age, sex and practice with up to 5 patients without polymyalgia rheumatica. Patients were followed until their first vascular event (cardiovascular, cerebrovascular, peripheral vascular) or the end of available records (May 2011). All participants were free of vascular disease before the diagnosis of polymyalgia rheumatica (or matched date). We used Cox regression models to compare time to first vascular event in patients with and without polymyalgia rheumatica.ResultsA total of 3249 patients with polymyalgia rheumatica and 12 735 patients without were included in the final sample. Over a median follow-up period of 7.8 (interquartile range 3.3-12.4) years, the rate of vascular events was higher among patients with polymyalgia rheumatica than among those without (36.1 v. 12.2 per 1000 person-years; adjusted hazard ratio 2.6, 95% confidence interval 2.4-2.9). The increased risk of a vascular event was similar for each vascular disease end point. The magnitude of risk was higher in early disease and in patients younger than 60 years at diagnosis.InterpretationPatients with polymyalgia rheumatica have an increased risk of vascular events. This risk is greatest in the youngest age groups. As with other forms of inflammatory arthritis, patients with polymyalgia rheumatica should have their vascular risk factors identified and actively managed to reduce this excess risk.
| S-EPMC4162802 | biostudies-literature
Project description:Polymyalgia rheumatica (PMR) and giant-cell arteritis (GCA) with symptoms of PMR share some pathophysiologic features. Interleukin 6 (IL-6) levels are elevated in both groups. We investigated the effect of tocilizumab (TCZ), an IL-6 inhibitor, in both populations and whether there were any differences regarding effectiveness and safety between them. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by searching the following databases: PubMed, PMC, Medline, Scopus, Cochrane Library, and ClincalTrials.gov. We found eight articles including one systematic review, one randomized controlled trial (RCT), one posthoc analysis of an RCT, and five observational studies. A total of 668 patients were included in this study. After a comprehensive analysis, we can only infer that there is insufficient evidence to suggest TCZ as monotherapy. Nevertheless, using TCZ in combination with glucocorticoid can be an effective therapeutic option.
| S-EPMC9435397 | biostudies-literature
Project description:Polymyalgia rheumatica (PMR) is a chronic inflammatory disease which affects the connective vascular tissue, characterized by pain accompanied by morning stiffness, predominantly of the neck muscles, hip and shoulder girdle. Usually, patients with this disease are >50 years of age and biological inflammatory syndrome is present with an increase in both the erythrocyte sedimentation rate and C-reactive protein levels, aspects similar to giant cell arteritis. The aim of the present review was to depict the current pathogenic hypothesis, diagnostic and treatment approach for patients with PMR, and novelties since the development of the currently used 2012 European League Against Rheumatism and American College of Rheumatology provisional classification criteria. PMR is a prevalent disease that can occasionally prove difficult to diagnose and treat. Possibly, the most abundant type of evidence and data revealed over the past decade have been acquired through musculoskeletal imaging, with implications in diagnosis, disease monitoring and relapse, prognosis and changes with treatment. Further research on pathophysiology is required to gain a deeper understanding of the underlying processes, which will serve as the foundation for future personalized treatments. In addition, there is an increasing demand for improved diagnostic techniques, which should include a further development of various imaging modalities, in order to provide accurate diagnosis and appropriate therapy.
| S-EPMC10623218 | biostudies-literature
Project description:ObjectivesTo compare clinical characteristics, imaging findings and treatment requirements of patients with immune checkpoint inhibitor-mediated polymyalgia rheumatica (ICI-PMR) and primary PMR.MethodsThis single centre, retrospective cohort study compared ICI-PMR in patients with cancer (n = 15) to patients with primary PMR (n = 37). A comparison was made between clinical symptoms, laboratory markers, ultrasonography, 18F-FDG-PET/CT findings and treatment requirements related to PMR.ResultsPatients with ICI-PMR less frequently fulfilled the EULAR/ACR classification criteria for PMR (66.7%) than patients with primary PMR (97.3%). Morning stiffness, weight loss and elevation of the ESR were less frequently seen in patients with ICI-PMR. No differences were observed regarding the presence of inflammatory lesions on ultrasound of the shoulders and hips between the two groups. The Leuven and the Leuven/Groningen 18F-FDG-PET/CT scores were significantly lower in the ICI-PMR group. Finally, the ICI-PMR group could be managed with lower glucocorticoid doses than the primary PMR group, while this treatment could be discontinued more quickly.ConclusionOur findings indicate that ICI-PMR may have a milder course with less intense inflammation than primary PMR. ICI-PMR can be managed with a relatively low glucocorticoid dose. Our study underscores that ICI-PMR should be regarded as a PMR-like syndrome.
| S-EPMC11781573 | biostudies-literature
Project description:To assess the rate of PMR who, during the follow-up, undergo a diagnostic shift as well as to assess which clinical, laboratory and US findings are associated to a diagnostic shift and predict the long-term evolution of PMR. All PMR followed-up for at least 12 months were included. According to the US procedures performed at diagnosis, patients were subdivided into four subgroups. Clinical data from follow-up visits at 12, 24, 48 and 60 months, including a diagnostic shift, the number of relapses and immunosuppressive and steroid treatment, were recorded. A total of 201 patients were included. During the follow-up, up to 60% had a change in diagnosis. Bilateral LHBT was associated with persistence in PMR diagnosis, whereas GH synovitis and RF positivity to a diagnostic shift. Patients undergoing diagnostic shift had a higher frequency of GH synovitis, shoulder PD, higher CRP, WBC, PLT and Hb and longer time to achieve remission, while those maintaining diagnosis had bilateral exudative LHBT and SA-SD bursitis, higher ESR, lower Hb and shorter time to remission. Cluster analysis identified a subgroup of older patients, with lower CRP, WBC, PLT and Hb, lower PD signal or peripheral synovitis who had a higher persistence in PMR diagnosis, suffered from more flares and took more GCs. Most PMR have their diagnosis changed during follow-up. The early use of the US is associated with a lower dosage of GCs. Patients with a definite subset of clinical, laboratory and US findings seem to be more prone to maintain the diagnosis of PMR.
| S-EPMC10543828 | biostudies-literature
Project description:Background and aimComorbidities are known to exist in many rheumatological conditions. Polymyalgia rheumatica (PMR) is a common inflammatory rheumatological condition affecting older people which, prior to effective treatment, causes severe disability. Our understanding of associated comorbidities in PMR is based only on case reports or series and small cohort studies. The objective of this study is to review systematically the existing literature on the comorbidities associated with PMR.MethodsMEDLINE, EMBASE, PsycINFO and CINAHL databases were searched for original observational research from inception to November 2016. Papers containing the words 'Polymyalgia Rheumatica' OR 'Giant Cell Arteritis' OR the terms 'PMR' OR 'GCA' were included. Article titles were reviewed based on pre-defined criteria by two reviewers. Following selection for inclusion, studies were quality assessed using the Newcastle-Ottawa tool and data were extracted.ResultsA total of 17,329 papers were reviewed and 41 were incorporated in this review, including three published after the search took place. Wide variations were found in study design, comorbidities reported and populations studied. Positive associations were found between PMR diagnosis and stroke, cardiovascular disease, peripheral arterial disease, diverticular disease and hypothyroidism. Two studies reported a positive association between PMR and overall malignancy rate. Seven studies reported an association between PMR and specific types of cancer, such as leukaemia, lymphoma, myeloproliferative disease and specified solid tumours, although nine studies found either no or negative association between cancer and PMR.ConclusionQuantification of the prevalence of comorbidities in PMR is important to accurately plan service provision and enable identification of cases of PMR which may be more difficult to treat. This review highlights that research into comorbidities in PMR is, overall, methodologically inadequate and does not comprehensively cover all comorbidities. Future studies should consider a range of comorbidities in patients with a validated diagnosis of PMR in representative populations.
| S-EPMC6247740 | biostudies-literature
Project description:ObjectivePlatelet activation is thought to participate in polymyalgia rheumatica (PMR) pathogenesis. Upon platelet activation, mitochondria are expelled into the extracellular space. However, whether extracellular mitochondria are present in patients with PMR and whether they can induce platelet activation is not known.MethodsTo investigate this, we measured markers of platelet activation (thrombospondin-1 [TSP-1]), mitochondrial-derived N-formyl methionine peptide (fMET), and autoantibodies directed toward specific mitochondrial antigen mitofusin-1 (MFN1) by enzyme-linked immunosorbent assay in plasma of healthy controls (HCs, n = 30) and patients with PMR without giant cell arteritis (GCA) (n = 45) and patients with PMR with GCA (n = 9) before and after treatment with glucocorticoid therapy. Ultrapure mitochondria were opsonized with plasma from patients with PMR without GCA (n = 45) or HCs (n = 10) and were subsequently incubated with HC platelets. Platelet activation was assessed by P-selectin levels using flow cytometry.ResultsPlasma levels of anti-MFN1 IgG were elevated in patients with PMR with and without GCA before glucocorticoid therapy when compared with HCs (P < 0.01 for both groups). Levels of anti-MFN1 IgG significantly reduced after treatment with glucocorticoids in both groups (P < 0.01). Levels of fMET were also significantly higher in patients with PMR with and without GCA before glucocorticoid therapy in comparison with HCs (P < 0.001 and P < 0.01, respectively). However, the levels of fMET only dropped significantly after therapy in patients with PMR without GCA (P < 0.001). Plasma levels of TSP-1 were elevated in patients with PMR with and without GCA before glucocorticoid therapy when compared to HC (P < 0.001 for both groups). After glucocorticoid therapy, plasma levels of TSP-1 decreased significantly only in patients with PMR without GCA (P = 0.023). Mitochondria opsonized with plasma from patients with PMR without GCA induced higher platelet activation regardless of treatment status as compared with plasma from HCs (P < 0.0001 and P < 0.01 for pretreatment and posttreatment).ConclusionOur results indicate increased platelet activation and the presence of mitochondrial antigens and antibodies in the circulation of patients with PMR. Blocking mitochondrial-mediated platelet activation may reduce inflammation in patients with PMR, with potential therapeutic implications.
| S-EPMC11897803 | biostudies-literature
Project description:BackgroundPrevious studies have assessed the association between antidiabetic drugs and stroke risk, but the results are inconsistent. Mendelian randomization (MR) was used to assess effects of antidiabetic drugs on stroke risk.MethodsWe selected blood glucose-lowering variants in genes encoding antidiabetic drugs targets from genome-wide association studies (GWAS). A two-sample MR and Colocalization analyses were applied to examine associations between antidiabetic drugs and the risk of stroke. For antidiabetic agents that had effect on stroke risk, an independent blood glucose GWAS summary data was used for further verification.ResultsGenetic proxies for sulfonylureas targets were associated with reduced risk of any stroke (OR=0.062, 95% CI 0.013-0.295, P=4.65×10－4) and any ischemic stroke (OR=0.055, 95% CI 0.010-0.289, P=6.25×10－4), but not with intracranial hemorrhage. Colocalization supported shared casual variants for blood glucose with any stroke and any ischemic stroke within the encoding genes for sulfonylureas targets (KCNJ11 and ABCC8) (posterior probability>0.7). Furthermore, genetic variants in the targets of insulin/insulin analogues, glucagon-like peptide-1 analogues, thiazolidinediones, and metformin were not associated with the risk of any stroke, any ischemic stroke and intracranial hemorrhage. The association was consistent in the analysis of sulfonylureas with stroke risk using an independent blood glucose GWAS summary data.ConclusionsOur findings showed that genetic proxies for sulfonylureas targets by lowering blood glucose were associated with a lower risk of any stroke and any ischemic stroke. The study might be of great significance to guide the selection of glucose-lowering drugs in individuals at high risk of stroke.
| S-EPMC10544120 | biostudies-literature
Project description: Not available
| S-EPMC7225140 | biostudies-literature
Project description: Not available
| S-EPMC10942171 | biostudies-literature