Rheumatoid arthritis (RA) is an autoimmune disease associated with synovitis and cartilage destruction. Ultrasound (US)-driven sonodynamic therapy (SDT) possess a good application prospect in RA ...therapy because of its non-invasiveness and strong tissue penetration capabilities, which can kill activated synovial inflammatory cells. Nevertheless, the tiny accumulation of sonosensitizers in the joints and the hypoxic synovial microenvironment severely limit the therapeutic effect of SDT. Hence, we developed a sonosensitizer spafloxacin (SPX) doped and human serum albumin (HSA) loaded concave-cubic rhodium (Rh) nanozyme (Rh/SPX-HSA) to realize mutual-reinforcing SDT during ultrasonic activation. On the one hand, SPX would cause mitochondrial dysfunction by inducing excessive reactive oxygen species (ROS) production, thus suppressing fibroblast-like synoviocyte (FLS) under US conditions. On the other hand, concave-cubic rhodium was utilized as a nanozyme with endogenous peroxidase (POD) and catalase (CAT)-like enzyme activities, which not only relieved the hypoxia of the joint to resist angiogenesis, but also enormously ascended the SDT efficacy by rising 1O2 levels. Interestingly, the activity of nanozymes was also improved by the ultrasonic cavitation effect, thereby realizing mutual-reinforcing SDT. Overall, our strategy provided Rh-based to achieve effective SDT under hypoxic microenvironment, which offered a promising prospect for highly efficient treatment of RA.
The COVID-19 pandemic has significantly changed the understanding of the safety profile of therapies for immunoinflammatory rheumatic diseases (IRDs). This is primarily due to the negative impact of ...a number of basic anti-inflammatory drugs (DMARDs) and biological DMARDs on the course and outcomes of a new coronavirus infection. A number of studies have shown that anti-B-cell therapy (rituximab) gave a statistically significant increase in the risk of severe COVID-19 and an increase in mortality. At the same time, the analysis of real clinical practice data dictated the need to establish a number of restrictions on the use of certain classes of biological DMARDs and to search for alternative therapy programs to maintain control over disease activity.Purpose of the study – to evaluate the efficacy and safety of the drug Artlegia® (olokizumab), solution for subcuta neous injection, 160 mg/ml – 0.4 ml, manufactured by R-Pharm JSC, Russia) for the treatment of patients with rheuma toid arthritis in real clinical practice after switching with rituximab during the COVID-19 pandemic.Materials and methods. The study included 14 patients with a confirmed diagnosis of rheumatoid arthritis (RA), who were previously on rituximab therapy at a dose of 1000–500 mg twice with an interval of 2 weeks, who received at least one course of therapy with this drug. As RA worsened, patients were switched to olokizumab against the background of standard DMARDs. At 4, 8, 12 weeks after the switch, the severity of pain was assessed on the VAS scale, the number of painful and swollen joints (TJC28 and TSC28), the level of acute phase markers of inflammation, the DAS28 disease activity index calculated using ESR and CRP, and the CDAI (clinical activity index), functional state index HAQ, as well as assessment of the safety profile of therapy.Results. Data analysis was performed using median values (Me) were used for data analysis. A significant decrease of TJC28 was after the injection of olokizumab (Artlegia®) in 8 and 12 weeks (Me baseline = 10; Me 8 weeks = 4; Me 12 weeks = 4; p<0.05) and a decrease of TSC28 in 4, 8 and 12 weeks (Me baseline = 9; Me 4 weeks = 3.5; Me 8 weeks = 2.5; Me 12 weeks = 2.0; p<0.05). Laboratory markers of inflammation showed a decrease in CRP and ESR levels after 4 weeks of treatment (CRP: Me baseline = 21, Me 4 weeks = 1 (p<0.05); ESR: Me baseline = 31, Me 4 weeks = 7 (p<0.05)). Positive dynamics persisted at 8 and 12 weeks (CRP: Me 8 weeks = 1, Me 12 weeks = 0; ESR: Me 8 weeks = 4, Me 12 weeks = 5). The level of CRP by the fourth week 4 became within the normal range, regardless of the initial values. All activity indices improved from the fourth week in each evaluation period compared to baseline: DAS28-ESR: Me baseline = 5.52, Me 4 weeks = 3.59, Me 8 weeks = 3.33, Me 12 weeks = 3.22 (p<0.05); DAS28-CRP: Me baseline = 5.39, Me 4 weeks = 3.71, Me 8 weeks = 3.35, Me 12 weeks = 3.45 (p<0.05); CDAI: Me baseline = 28.5, Me 4 weeks = 18.0, Me 8 weeks = 16.5, Me 12 weeks = 16.0 (p<0.05). All patients showed a reduction in pain (VAS scale) by week 8. The functional status of patients, according to the HAQ index, showed a significant decrease only by the 12th week of the study: Me baseline = 1.62, Me 12 weeks = 1.31 (p<0.05).Conclusion. The study found that switching from rituximab to olokizumab was effective and safe during the COVID-19 pandemic.
Individuals with rheumatoid arthritis (RA) benefit from early diagnosis and initiation of therapy. There can be delays in both due to diagnostic uncertainties. Imaging modalities, including magnetic ...resonance imaging (MRI), can detect inflammation earlier than clinical examination alone in early RA patients. Furthermore, the predictive role of MRI for the future development of RA has recently been explored in ‘at-risk’ individuals. This review details the use of MRI in early and undifferentiated arthritis and summarises the studies to date in individuals at risk of RA.
Poor O2 supply to the infiltrated immune cells in the joint synovium of rheumatoid arthritis (RA) up-regulates hypoxia-inducible factor (HIF-1α) expression and induces reactive oxygen species (ROS) ...generation, both of which exacerbate synovial inflammation. Synovial inflammation in RA can be resolved by eliminating pro-inflammatory M1 macrophages and inducing anti-inflammatory M2 macrophages. Because hypoxia and ROS in the RA synovium play a crucial role in the induction of M1 macrophages and reduction of M2 macrophages, herein, we develop manganese ferrite and ceria nanoparticle-anchored mesoporous silica nanoparticles (MFC-MSNs) that can synergistically scavenge ROS and produce O2 for reducing M1 macrophage levels and inducing M2 macrophages for RA treatment. MFC-MSNs exhibit a synergistic effect on O2 generation and ROS scavenging that is attributed to the complementary reaction of ceria nanoparticles (NPs) that can scavenge intermediate hydroxyl radicals generated by manganese ferrite NPs in the process of O2 generation during the Fenton reaction, leading to the efficient polarization of M1 to M2 macrophages both in vitro and in vivo. Intra-articular administration of MFC-MSNs to rat RA models alleviated hypoxia, inflammation, and pathological features in the joint. Furthermore, MSNs were used as a drug-delivery vehicle, releasing the anti-rheumatic drug methotrexate in a sustained manner to augment the therapeutic effect of MFC-MSNs. This study highlights the therapeutic potential of MFC-MSNs that simultaneously generate O2 and scavenge ROS, subsequently driving inflammatory macrophages to the anti-inflammatory subtype for RA treatment.
Abstract
Objectives
To estimate prevalence rates and identify baseline predictors of adverse events (AEs) over the first year of treatment in patients with RA starting MTX.
Methods
Data came from the ...UK Rheumatoid Arthritis Medication Study (RAMS), a prospective cohort of patients with RA starting MTX. This analysis included patients aged ≥18 years with physician diagnosed RA and symptom duration ≤2 years, who were commencing MTX for the first time. AEs were recorded by interviewing patients at 6- and 12-month follow-up visits. The period prevalence rates of AEs are reported for 0–6 months, 6–12 months and 0–12 months of follow-up. The associations between baseline characteristics and AEs were assessed using multivariable logistic regression.
Results
A total of 1069 patients were included in the analysis. Overall, 77.5% experienced at least one AE. The most commonly reported AEs were: gastrointestinal (42.0%), neurological (28.6%), mucocutaneous (26.0%), pulmonary (20.9%), elevated alanine transaminase (18.0%) and haematological AEs (5.6%). Factors associated with increased odds of AEs were: women vs men (gastrointestinal, mucocutaneous, neurological) and alcohol consumption (nausea, alopecia, mucocutaneous). Older age, higher estimated glomerular filtration rate and alcohol consumption were associated with less reporting of haematological AEs.
Conclusions
AEs were common among patients over the first year of MTX, although most were not serious. Knowledge of the rates and factors associated with AE occurrence are valuable when communicating risks prior to commencing MTX. This can help patients make informed decisions whether to start MTX, potentially increasing adherence to treatment.
Background For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims ...to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments. Methods We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs. Results Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. Conclusions The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.
Biosimilars represent a novel category in the world of follow-up medicinal products with the requirement that they are highly similar but not identical to an approved originator biologic medicine, ...with no clinically meaningful differences in safety, purity, and potency. In this review, we discuss recent pivotal biosimilar developments for anti-inflammatory therapy in rheumatology, gastroenterology, and dermatology, and the influence of biosimilar availability on patients and payers. Finally, we provide our perspective on the evolution of biosimilar use in these indications in the United States (US) and in Europe and on where this evolution in biopharmaceuticals may lead in the future. Although biosimilars are commonly used in the European Union (EU), there will be an inevitable sea change of acceptance by clinicians, patients, payers, and regulators in the US. It is paramount to educate about biosimilarity, highlighting currently available data gathered from other geographies, in addition to gradually providing clinicians and patients with the necessary experience with these agents ultimately restoring competition in the biologics landscape.
Objective
Rheumatoid arthritis (RA) is a morbid, mortal, and costly condition without a cure. Treatments for RA have expanded over the last 2 decades, and direct medical costs may differ by types of ...treatments. There has not been a systematic literature review since the introduction of new RA treatments, including biologic disease‐modifying antirheumatic drugs (bDMARDs).
Methods
We conducted a systematic literature review with meta‐analysis of direct medical costs associated with RA patients cared for in the US since the marketing of the first bDMARD. Standard search strategies and sources were used, and data were extracted independently by 2 reviewers. The methods and quality of included studies were assessed. Total direct medical costs as well as RA‐specific costs were calculated using random‐effects meta‐analysis. Subgroups of interest included Medicare patients and those using bDMARDs.
Results
We found 541 potentially relevant studies, and 12 articles met the selection criteria. The quality of studies varied: one‐third were poor, one‐third were fair, and one‐third were good. Total direct medical costs were estimated at $12,509 (95% confidence interval 95% CI 7,451–21,001) for all RA patients using any treatment regimen and $36,053 (95% CI 32,138–40,445) for bDMARD users. RA‐specific costs were $3,723 (95% CI 2,408–5,762) for all RA patients using any treatment regimen and $20,262 (95% CI 17,480–23,487) for bDMARD users.
Conclusion
The total and disease‐specific direct medical costs for patients with RA is substantial. Among bDMARD users, the cost of RA care is more than half of all direct medical costs.
Background:Rheumatoid arthritis (RA) has extra-articular manifestations of cardiovascular diseases and is associated with a high mortality rate in Western populations. This study aimed to investigate ...the risk of acute coronary syndrome (ACS) and atrial fibrillation (AF) associated with RA in a Korean population.Methods and Results:Patients were selected from a senior cohort from the Korean National Health Insurance Service in 2002, and followed until 31 December 2015. Patients with newly developed ACS and AF were identified and compared with controls for a 10-year period using time-dependent propensity and risk-set matching. A total of 4,217 incident RA patients and their 8,432 controls comprised the incident RA and matched cohorts, respectively. ACS was identified during 24,642 person-years incidence rate (IR) 402 per 10,000 person-years, 95% confidence interval (CI) 330–489 among the RA cohort. In the matched cohort, 141 ACS patients were identified during 50,011 person-years (IR 282 per 100,000 person-years, 95% CI 239–333). RA patients were 1.43-fold more likely to develop ACS than the matched controls hazard ratio (HR) 1.43, 95% CI 1.10–1.84, but showed similar occurrence risk of AF (HR 1.06, 95% CI 0.83–1.35).Conclusions:A higher risk for ACS and a similar risk for AF were found by risk-set matched analysis in a senior RA cohort compared with the control, using Korean nationwide long-term data.
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