Treatment with adalimumab in patients with chronic inflammatory rheumatic diseases: a study of treatment trajectories on a patient level in routine care
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PROVIDER: S-EPMC10492472 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe mechanism explaining low cholesterol concentrations in chronic inflammatory rheumatic disease (CIRD) is incompletely understood. We hypothesized that chronic inflammation impairs the functionality of high-density lipoprotein (HDL), for example, by oxidative processes.ObjectivesAssessment of oxidized HDL (HDLox), a marker of dysfunctional HDL, in newly diagnosed patients with CIRD before and after initiation of immunosuppressive therapy and comparison of HDLox values of patients with CIRD to non-CIRD controls.DesignProspective observational trial.MethodsThe study was conducted on 44 newly diagnosed CIRD patients, who were initiated on immunosuppressive therapy (baseline). A total of 136 patients without CIRD served as control. Lipid profiles including HDLox levels and C-reactive protein (CRP) were measured in both groups at baseline. In CIRD patients, measurements were repeated 12 weeks after baseline. Validated outcome tools for disease activity and function were assessed at baseline and 12 weeks.ResultsA total of 33 (75%) patients with rheumatoid arthritis, 7(16%) with axial spondyloarthritis, and 4 (9%) with systemic lupus erythematosus were included. Groups were comparable for age and BMI. CIRD patients had higher HDLox concentrations (1.57 versus 0.78, p = 0.02) and tended to have lower low-density lipoprotein cholesterol, HDL cholesterol, and cholesterol concentrations compared to controls. HDLox (1.57 versus 1.4, p = 0.26) and CRP levels (2.1 versus 0.7 mg/dl, p < 0.01) decreased in CIRD patients from baseline to follow-up.ConclusionCIRD is associated with an impairment of the anti-inflammatory properties of HDL as reflected by an increase in HDLox concentrations. This effect may contribute to the increased cardiovascular risk in chronic inflammatory diseases.
| S-EPMC10462425 | biostudies-literature
Project description:ObjectiveTo explore how patients with chronic inflammatory rheumatic diseases (CIRDs) coped with their disease during the COVID-19 pandemic and to identify possible predictive factors of SARS-CoV-2 infection in this population.MethodsPatients followed in a single rheumatology department in France or registered on the Spondy+ platform, a secure e-health platform for spondyloarthritis patients, were invited to complete a questionnaire focused on their experiences around COVID19 symptoms, testing and medications access during the lockdown period. Descriptive statistics were used to report questionnaire's results. Factors associated with COVID-19 or with treatment discontinuation were assessed by logistic regression.ResultsWe obtained 655 answers from the 2,081 contacted patients: 474 with spondyloarthritis, 129 with rheumatoid arthritis and 52 with psoriatic arthritis. The population was predominantly female (61.8%) with a mean age of 51.0±13.4 years. Incidence of COVID-19 was 6.9% (95%CI: 5.1-9.2%), including 12 confirmed and 33 highly suspicious cases. No death was observed and five patients needed to be hospitalized. Factors independently associated with an increased risk of infection were SARS-CoV-2 exposure, younger age and non-smoking. More than 30% of the patients suspended or decreased the dosage of one of their drugs during the lockdown period. This was followed in 63.4% of them by increased disease activity. Modifications were mostly motivated by fear of contagion (79.3%).ConclusionWe did not observe any increase of incidence or severity of COVID-19 in patients suffering of the 3 most common CIRDs. This survey also adds evidence of the safety of anti-rheumatic drugs use regarding COVID-19.
| S-EPMC7605756 | biostudies-literature
Project description:Inflammatory rheumatic diseases (IRDs), encompassing a broad spectrum of chronic disorders, typically necessitate prolonged therapeutic intervention. Nevertheless, these diseases can sometimes manifest as severe emergencies requiring prompt and extensive medical intervention. Urgent intervention is essential for effectively recognizing and managing these situations, as they have the potential to be life-threatening and can result in severe morbidity and mortality. Emergencies in IRDs can occur with different frequencies and manifestations, including nervous system issues, severe infections, thrombosis-emboli, renal crises, gastrointestinal issues, and cardiovascular events. The fact that these events can occur across different IRDs underscores the necessity for heightened awareness and readiness among healthcare professionals. The pathophysiologic mechanisms that cause rheumatic emergencies are complex and involve multiple factors. These emergencies frequently arise due to the interplay between the inflammatory characteristics of rheumatic diseases and different systemic triggers. Early detection and treatment can have a substantial impact on an individual's prognosis in cases of severe and life-threatening disorders that require prompt recognition. Rapid decision-making and urgent care are required to effectively address rheumatic emergencies, as well as the implementation of a diagnostic flowchart. This article provides an overview of the emergencies linked to IRDs, classifying and assessing them individually. This article aims to enhance healthcare professionals' knowledge and awareness of critical situations by examining current recommendations and pathophysiological information. Implementing standardized diagnostic and treatment methods, providing patient education, and conducting continuing research into the underlying mechanisms are essential for enhancing the management of these critical situations and improving patient outcomes.
| S-EPMC11343811 | biostudies-literature
Project description:BackgroundIn pediatric rheumatic diseases (PRD), adalimumab is dosed using fixed weight-based bands irrespective of methotrexate co-treatment, disease activity (DA) or other factors that might influence adalimumab pharmacokinetics (PK). In rheumatoid arthritis (RA) adalimumab exposure between 2-8 mg/L is associated with clinical response. PRD data on adalimumab is scarce. Therefore, this study aimed to analyze adalimumab PK and its variability in PRD treated with/without methotrexate.MethodsA two-center prospective study in PRD patients aged 2-18 years treated with adalimumab and methotrexate (GA-M) or adalimumab alone (GA) for ≥ 12 weeks was performed. Adalimumab concentrations were collected 1-9 (maximum concentration; Cmax), and 10-14 days (minimum concentration; Cmin) during ≥ 12 weeks following adalimumab start. Concentrations were analyzed with enzyme-linked immunosorbent assay (lower limit of quantification: 0.5 mg/L). Log-normalized Cmin were compared between GA-M and GA using a standard t-test.ResultsTwenty-eight patients (14 per group), diagnosed with juvenile idiopathic arthritis (71.4%), non-infectious uveitis (25%) or chronic recurrent multifocal osteomyelitis (3.6%) completed the study. GA-M included more females (71.4%; GA 35.7%, p = 0.13). At first study visit, children in GA-M had a slightly longer exposure to adalimumab (17.8 months [IQR 9.6, 21.6]) compared to GA (15.8 months [IQR 8.5, 30.8], p = 0.8). Adalimumab dosing was similar between both groups (median dose 40 mg every 14 days) and observed DA was low. Children in GA-M had a 27% higher median overall exposure compared to GA, although median Cmin adalimumab values were statistically not different (p = 0.3). Cmin values ≥ 8 mg/L (upper limit RA) were more frequently observed in GA-M versus GA (79% versus 64%). Overall, a wide range of Cmin values was observed in PRD (0.5 to 26 mg/L).ConclusionThis study revealed a high heterogeneity in adalimumab exposure in PRD. Adalimumab exposure tended to be higher with methotrexate co-treatment compared to adalimumab monotherapy although differences were not statistically significant. Most children showed adalimumab exposure exceeding those reported for RA with clinical response, particularly with methotrexate co-treatment. This highlights the need of further investigations to establish model-based personalized treatment strategies in PRD to avoid under- and overexposure.Trial registrationNCT04042792 , registered 02.08.2019.
| S-EPMC10763375 | biostudies-literature
Project description:BackgroundMethotrexate (MTX) is the most commonly prescribed disease-modifying drug in the treatment of rheumatic diseases. Regular laboratory testing is recommended to recognize side effects, such as hepatotoxicity and myelotoxicity as well as decreases in renal function that may cause toxic MTX accumulation. Additionally, folic acid is recommended as prophylaxis against specific side effects. In this study we investigated whether laboratory monitoring and prescription of folic acid took place according to published recommendations.Material and methodsClaims data from the statutory health insurance from 1 January 2009 to 31 December 2013 were retrospectively analyzed. A total of 40,087 adults with a rheumatic diagnosis (ICD10 codes M05-M18), no malignant disease and no previous MTX prescription within 12 months were extracted from the InGef (Institute for Applied Health Research in Berlin, formerly Health Risk Institute) research database. The frequency of recommended laboratory testing, appointments with rheumatologists and the prescription of folic acid prophylaxis were investigated.ResultsOf the patients 12,451 began treatment with MTX in the observation period. Between 42% and 46% of recommended blood counts, liver values and kidney function tests and 14% of urinalyses were performed according to recommendations. Of the patients 84% were seen regularly by a rheumatologist and 74% received a prescription for prophylactic folic acid. Serious conditions potentially resulting from MTX treatment were observed in 0.7-3.5 cases/1000 person years.DiscussionLaboratory monitoring in the context of MTX treatment is carried out less frequently than recommended in the literature. Potential MTX-associated serious complications are rare from a practice perspective. On the one hand solutions are needed for a better coordination of laboratory monitoring. On the other hand more empirical evidence is needed regarding the benefits of laboratory monitoring and the appropriate intervals thereof.
| S-EPMC8189943 | biostudies-literature
Project description:Objective. Colchicine is an alkaloid that is used to alleviate acute gout and to prevent acute attacks of familial Mediterranean fever (FMF). However, it is not beneficial when given during the occurrence of an acute episode of FMF. It is believed that colchicine exerts its anti-inflammatory effect through direct interaction with microtubules. We aim to study the molecular basis of colchicine action by analysing the effect of this drug on global gene expression of HUVEC (human umbilical vein endothelial cell line) cells. Methods. HUVEC cells were exposed to various concentrations of colchicine and were harvested at different time points. Ribonucleic acid was extracted, amplified, reverse transcribed and hybridized to complementary deoxyribonucleic acid microarrrays containing more than 40,000 probes to human expressed sequence tags. This approach enabled us to have a global look at the transcriptional response induced by colchicine treatment. Results. Colchicine changed the expression of many genes in HUVEC cells following exposure to a concentration of 100 ng/ml or higher. Following short exposure (30 or 120 min), colchicine affected genes known to be involved in the cell cycle and its regulation. However, change in expression of genes involved in neutrophil migration or other inflammatory processes were observed mainly after 12 to 24 h. Conclusions. The anti-inflammatory effect of colchicine may be mediated not only through direct interaction with microtubules but also through changes at the transcriptional level. This latter effect apparently requires a higher concentration and a longer time to occur. This can explain the observation that colchicine does not have an immediate effect when given during an acute attack of FMF. A dose response design type examines the relationship between the size of the administered dose and the extent of the response of the organism(s). Using regression correlation
2006-01-24 | E-GEOD-4090 | biostudies-arrayexpress
Project description:Objective. Colchicine is an alkaloid that is used to alleviate acute gout and to prevent acute attacks of familial Mediterranean fever (FMF). However, it is not beneficial when given during the occurrence of an acute episode of FMF. It is believed that colchicine exerts its anti-inflammatory effect through direct interaction with microtubules. We aim to study the molecular basis of colchicine action by analysing the effect of this drug on global gene expression of HUVEC (human umbilical vein endothelial cell line) cells. Methods. HUVEC cells were exposed to various concentrations of colchicine and were harvested at different time points. Ribonucleic acid was extracted, amplified, reverse transcribed and hybridized to complementary deoxyribonucleic acid microarrrays containing more than 40,000 probes to human expressed sequence tags. This approach enabled us to have a global look at the transcriptional response induced by colchicine treatment. Results. Colchicine changed the expression of many genes in HUVEC cells following exposure to a concentration of 100 ng/ml or higher. Following short exposure (30 or 120 min), colchicine affected genes known to be involved in the cell cycle and its regulation. However, change in expression of genes involved in neutrophil migration or other inflammatory processes were observed mainly after 12 to 24 h. Conclusions. The anti-inflammatory effect of colchicine may be mediated not only through direct interaction with microtubules but also through changes at the transcriptional level. This latter effect apparently requires a higher concentration and a longer time to occur. This can explain the observation that colchicine does not have an immediate effect when given during an acute attack of FMF. A dose response design type examines the relationship between the size of the administered dose and the extent of the response of the organism(s). Keywords: dose_response_design
2006-01-25 | GSE4090 | GEO
Project description:ObjectiveCurrent management of patients with pediatric rheumatic diseases (PRD) should aim at achieving the best possible well-being. To identify sociodemographic/clinical characteristics, needed paramedical services and school accommodations associated with well-being in patients at inclusion in a French health network Réseau pour les Rhumatismes Inflammatoires Pédiatriques (RESRIP) that supports coordination of the patient's health pathway. To evaluate the evolution of well-being over time in this patients benefiting from such support.MethodsPatients > 3 years old enrolled in RESRIP (2013-2020) were included. At enrollment, data were collected on sociodemographic/clinical characteristics, ongoing medications, and paramedical and educational actions to be implemented by RESRIP. Well-being during the last 6 months was reported with a standardized questionnaire at enrollment and every 6 months. A well-being score was calculated with scores ranging from 0 to 18, 18 corresponding to absolute well-being. Patients were followed up from inclusion until June 2020.ResultsIn total, 406 patients were included and followed up for 36 months on average: 205 juvenile idiopathic arthritis, 68 connective tissue diseases, 81 auto-inflammatory diseases and 52 other diseases. The well-being score did not differ between the groups and improved significantly, by 0.04 score units, every 6 months (95% confidence interval [0.03; 0.06]). At inclusion, use of homeopathy, need for implementation of hypnosis or psychological support, occupational therapy or for adjustment of school tests were associated with worse well-being score.ConclusionWell-being seems associated more with the impact of chronic illness than the type of PRD underlining the importance of a comprehensive patient care.
| S-EPMC9990204 | biostudies-literature
Project description:The aim of this review is to focus attention on high quality diagnostics of systemic inflammatory rheumatic diseases. Though many steps in the diagnostic process from the first visit in a doctor's office till a final diagnosis have been established a lot of things still must be done to improve quality assurance and secure fast and safe transmission of data from one step to the next. Some procedures inherent in early high quality diagnostics need to be worked out. A number of elements can be improved, some stumble stones can be removed, and a tighter collaboration between actors at different levels in the line of action in clinical and laboratory medicine can be organized. Several proposals have been made by international working groups such as the IUIS International Autoantibody Standardization Committee, and the EASI steering group in collaboration with their national EASI teams. Practical exercises carried out for more than three decades by the European Consensus Finding Study Group have proven to very useful. The review points at several principles worked out by these international expert groups can be useful in actual daily practice also in rheumatology. The hope is that the presentation will give rise to a continued discussion on how to link different parts of the diagnostic process together and strengthen collaboration between all teams involved in the diagnostic chain. The ultimate measure of success will be better clinical outcomes for patients and increased satisfaction in their families.
| S-EPMC4389069 | biostudies-other
Project description:BackgroundThe course of novel coronavirus disease 2019 (COVID-19) has been of special concern in patients with inflammatory rheumatic diseases (IRDs) due to the immune dysregulation that may be associated with these diseases and the medications used for IRDs, that may affect innate immune responses.ObjectiveIn this cohort study, we aimed to report the disease characteristics and variables associated with COVID-19 outcome among Turkish patients with IRDs.MethodsBetween April and June, 2020, 167 adult IRD patients with COVID-19 were registered from 31 centers in 14 cities in Turkey. Disease outcome was classified in 4 categories; (i) outpatient management, (ii) hospitalization without oxygen requirement, (iii) hospitalization with oxygen requirement, and (iv) intensive care unit (ICU) admission or death. Multivariable ordinal logistic regression analysis was conducted to determine variables associated with a worse outcome.Results165 patients (mean age: 50 ± 15.6 years, 58.2% female) were included. Twenty-four patients (14.5%) recovered under outpatient management, 141 (85.5%) were hospitalized, 49 (30%) required inpatient oxygen support, 22 (13%) were treated in the ICU (17 received invasive mechanic ventilation) and 16 (10%) died. Glucocorticoid use (OR: 4.53, 95%CI 1.65-12.76), chronic kidney disease (OR: 12.8, 95%CI 2.25-103.5), pulmonary disease (OR: 2.66, 95%CI 1.08-6.61) and obesity (OR: 3.7, 95%CI 1.01-13.87) were associated with a worse outcome. Biologic disease-modifying antirheumatic drugs (DMARDs) do not seem to affect COVID-19 outcome while conventional synthetic DMARDs may have a protective effect (OR: 0.36, 95%CI 0.17-0.75). Estimates for the associations between IRD diagnoses and outcome were inconclusive.ConclusionsAmong IRD patients with COVID-19, comorbidities and glucocorticoid use were associated with a worse outcome, while biologic DMARDs do not seem to be associated with a worse outcome.
| S-EPMC8086428 | biostudies-literature