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Pharmaceutics May 2024Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient's circulating drug levels. Using modelling and...
Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient's circulating drug levels. Using modelling and simulation, the aim of this study was to investigate whether adalimumab and etanercept biosimilar dosing intervals can be altered to achieve therapeutic drug levels at a faster/similar time compared to the recommended interval. RA patients starting subcutaneous Amgevita or Benepali (adalimumab and etanercept biosimilars, respectively) were recruited and underwent sparse serum sampling for drug concentrations. Drug levels were measured using commercially available kits. Pharmacokinetic data were analysed using a population approach (popPK) and potential covariates were investigated in models. Models were compared using goodness-of-fit criteria. Final models were selected and used to simulate alternative dosing intervals. Ten RA patients starting the adalimumab biosimilar and six patients starting the etanercept biosimilar were recruited. One-compartment PK models were used to describe the popPK models for both drugs; no significant covariates were found. Typical individual parameter estimates were used to simulate altered dosing intervals for both drugs. A simulation of dosing the etanercept biosimilar at a lower rate of every 10 days reached steady-state concentrations earlier than the usual dosing rate of every 7 days. Simulations of altered dosing intervals could form the basis for future personalised dosing studies, potentially saving costs whilst increasing efficacy.
PubMed: 38931826
DOI: 10.3390/pharmaceutics16060702 -
Pharmaceuticals (Basel, Switzerland) May 2024Rheumatoid arthritis (RA) is associated with significant systemic and local bone loss. The aim of this study was to assess whether or not 15-month tumor necrosis factor...
Rheumatoid arthritis (RA) is associated with significant systemic and local bone loss. The aim of this study was to assess whether or not 15-month tumor necrosis factor α inhibitor (TNFαI) therapy in combination with methotrexate (MTX) affects circulating levels of sclerostin (SOST) in female RA patients. Plasma levels of SOST were measured using immunoassays kits. Baseline SOST levels showed no significant differences between RA patients and control participants. Postmenopausal women with RA tended to have higher sclerostin levels than premenopausal woman with RA. After 15 months of treatment with TNFαI, plasma levels of SOST were decreased. Before starting biological therapy, circulating levels of SOST significantly correlated with the patient's age ( < 0.05) and the marker of inflammation, such as ESR ( < 0.05). Multivariate regression analysis showed that age was the only significant predictor for baseline SOST levels in women with RA (β = 0.008, = 0.028, R2 model = 0.293). Moreover, a positive correlation between SOST levels and the 28 joint disease activity score value based on the erythrocyte sedimentation rate (DAS28-ESR) was found at baseline ( < 0.05), as well as after 15 months of biological therapy ( < 0.05). Thus, plasma SOST levels may be helpful for monitoring the efficacy of TNFαI treatment in RA patients. According to our results, TNFαI, in combination with MTX, has a beneficial effect on bone turnover with a significant reduction in bone metabolism marker SOST.
PubMed: 38931334
DOI: 10.3390/ph17060666 -
Nutrients Jun 2024Osteoarthritis (OA) is a chronic degenerative joint disease that causes chronic pain, swelling, stiffness, disability, and significantly reduces the quality of life....
Osteoarthritis (OA) is a chronic degenerative joint disease that causes chronic pain, swelling, stiffness, disability, and significantly reduces the quality of life. Typically, OA is treated using painkillers and non-steroidal anti-inflammatory drugs (NSAIDs). While current pharmacologic treatments are common, their potential side effects have prompted exploration into functional dietary supplements. Recently, eggshell membrane (ESM) has emerged as a potential functional ingredient for joint and connective tissue disorders due to its clinical efficacy in relieving joint pain and stiffness. Despite promising clinical evidence, the effects of ESM on OA progression and its mechanism of action remain poorly understood. This study evaluated the efficacy of Ovomet, a powdered natural ESM, against joint pain and disease progression in a monosodium iodoacetate (MIA)-induced rodent model of OA in mice and rats. The results demonstrate that ESM significantly alleviates joint pain and attenuates articular cartilage destruction in both mice and rats that received oral supplementation for 5 days prior to OA induction and for 28 days thereafter. Interestingly, ESM significantly inhibited mRNA expression levels of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as inflammatory mediators, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase in the knee joint cartilage at the early stage of OA, within 7 days after OA induction. However, this effect was not observed in the late stage at 28 days after OA induction. ESM further attenuates the induction of protein expression for cartilage-degrading enzymes like matrix metalloproteinase (MMPs) 3 and 13, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), in the late-stage. In addition, MIA-induced reduction of the protein expression levels of cartilage components, cartilage oligomeric matrix protein (COMP), aggrecan (ACAN) and collagen type II α-1 chain (COL2α1), and cartilage extracellular matrix (ECM) synthesis promoting transcriptional factor SRY-Box 9 (SOX-9) were increased via ESM treatment in the cartilage tissue. Our findings suggest that Ovomet, a natural ESM powder, is a promising dietary functional ingredient that can alleviate pain, inflammatory response, and cartilage degradation associated with the progression of OA.
Topics: Animals; Egg Shell; Cartilage, Articular; Osteoarthritis; Male; Mice; Nitric Oxide Synthase Type II; Rats; Inflammation; Dietary Supplements; Cytokines; Disease Models, Animal; Rats, Sprague-Dawley; Arthralgia; Time Factors; Iodoacetic Acid; Anti-Inflammatory Agents
PubMed: 38931240
DOI: 10.3390/nu16121885 -
Molecules (Basel, Switzerland) Jun 2024The genus Strophantus belongs to the Apocynaceae family of flowering plants which grows primarily in tropical Africa. The plants are widely used in traditional herbal... (Review)
Review
The genus Strophantus belongs to the Apocynaceae family of flowering plants which grows primarily in tropical Africa. The plants are widely used in traditional herbal medicine. , in particular, is used for the treatment of, e.g., joint pain and rheumatoid arthritis, wound infections, head lice, diarrhea, snake bite, and eye conditions. Despite its widespread use, dedicated research characterizing its bioactive plant components is scarce. Investigations have focused mainly on its cardenolides because of their cardioactivity and historical use as cardiotonic. There are also studies concerning the antibacterial, antioxidant, and anti-inflammatory activity of plant extracts. This review summarizes the present knowledge surrounding the biochemical and analytical research on Strophantus, in general, and , in particular, and describes the current state of the field based on the available scientific literature.
Topics: Plant Extracts; Humans; Apocynaceae; Antioxidants; Animals; Anti-Inflammatory Agents; Phytochemicals; Anti-Bacterial Agents
PubMed: 38930911
DOI: 10.3390/molecules29122847 -
Molecules (Basel, Switzerland) Jun 2024Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on... (Review)
Review
Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl intoxication) has been verified over the past two decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes and type 2 diabetes, and in the prevention of intoxications. Low-dose ozone acts as a redox bioregulator: the restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase in the antioxidant repair markers, here mainly shown as a glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, and relevant data are displayed, evaluated and comprehensively discussed: the repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone-treated groups and depending on the indication, the stress markers are simultaneously reduced, and the redox system regains its balance.
Topics: Oxidative Stress; Ozone; Oxidation-Reduction; Humans; Mitochondria; Reactive Oxygen Species; Animals; Antioxidants; Biomarkers
PubMed: 38930804
DOI: 10.3390/molecules29122738 -
Microorganisms Jun 2024Prosthetic joint infection (PJI) is one of the most serious complications of joint replacement surgery among orthopedic surgeries and occurs in 1 to 2% of primary...
Prosthetic joint infection (PJI) is one of the most serious complications of joint replacement surgery among orthopedic surgeries and occurs in 1 to 2% of primary surgeries. Additionally, the cause of PJIs is mostly bacteria from the species, accounting for more than 98%, while fungi cause PJIs in only 1 to 2% of cases and can be difficult to manage. The current gold-standard microbiological method of culturing synovial fluid is time-consuming and produces false-negative and -positive results. This study aimed to identify a novel, accurate, and convenient molecular diagnostic method. The DreamDX primer-hydrolysis probe set was designed for the pan-bacterial and pan-fungal detection of DNA from pathogens that cause PJIs. The sensitivity and specificity of DreamDX primer-hydrolysis probes were 88.89% (95% CI, 56.50-99.43%) and 97.62% (95% CI, 87.68-99.88%), respectively, compared with the microbiological method of culturing synovial fluid, and receiver operating characteristic (ROC) area under the curve (AUC) was 0.9974 (*** < 0.0001). It could be concluded that the DreamDX primer-hydrolysis probes have outstanding potential as a molecular diagnostic method for identifying the causative agents of PJIs, and that host inflammatory markers are useful as adjuvants in the diagnosis of PJIs.
PubMed: 38930616
DOI: 10.3390/microorganisms12061234 -
Journal of Clinical Medicine Jun 2024: Lung ultrasound (LUS) is a tool of growing interest in Rheumatoid Arthritis (RA) oligo- symptomatic ILD to avoid. : We aimed to evaluate (i) the prevalence of pleural...
: Lung ultrasound (LUS) is a tool of growing interest in Rheumatoid Arthritis (RA) oligo- symptomatic ILD to avoid. : We aimed to evaluate (i) the prevalence of pleural (PLUS) and parenchymal (PAUS) abnormalities in LUS in the RA population and their possible correlation to biomarkers; (ii) the predictivity of gender, smoking habits, previous infections (past COVID-19 tuberculosis), and treatments; (iii) the differences in LUS between sexes. : We collected the data of 155 (15 early and 140 late) RA patients with mild respiratory symptoms, evaluating PLUS and PAUS, in fourteen lung areas and also summing the scores (LUS-T). : Only 13/155 (8.4%) were completely negative; LUS correlated to age (all parameters 0.0001), rheumatoid factor IgM (PLUS 0.0006, PAUS 0.02, LUS-T 0.001) and ACPA ( 0.001, 0.006, 0.001, respectively), and PLUS also correlated to IL6 ( 0.02). The male gender was predictive of all LUS evaluations ( 0.001, 0.05, 0.001, respectively), which were higher than in women ( 0.001, 0.01, 0.001, respectively). Other potential risk factors were independent, except biological treatments, which showed a low predictivity to PLUS ( < 0.05). We can conclude that LUS is a useful technique in RA low respiratory symptoms and correlates with age, the most important RA biomarkers, and male sex.
PubMed: 38930065
DOI: 10.3390/jcm13123534 -
Journal of Clinical Medicine Jun 2024Neuropsychiatric systemic lupus erythematosus (NPSLE) is a complication of systemic lupus erythematosus with diverse clinical presentations sharing common features with...
Neuropsychiatric systemic lupus erythematosus (NPSLE) is a complication of systemic lupus erythematosus with diverse clinical presentations sharing common features with variable neurologic disorders. Magnetic resonance imaging (MRI) may provide imaging evidence of structural brain abnormalities associated with symptoms of NPSLE. Serotonin syndrome is a toxidrome characterized by altered mental status, autonomic hyperactivity, and neuromuscular abnormalities. It is mostly caused by medications that increase serotonin and is rarely reported as a manifestation of neuropsychiatric lupus. We presented the case of a 24-year-old Taiwanese woman with a history of systemic lupus erythematosus diagnosed at 21 years of age. The initial clinical and laboratory presentations upon diagnosis included fever, arthritis, hypocomplementemia, positive antinuclear antibody, anti-double-stranded DNA antibody, and anti-ribosomal P antibody. Her condition once remained stable under oral glucocorticoids and immunosuppressants, but she developed sudden-onset consciousness disturbance, incoherent speech, and unsteady gait ten days before our assessment. A high fever of up to 39 °C with tremor and clonus occurred at the intensive care unit. Brain MRI revealed symmetric T2 hyperintensity without diffusion restriction over the bilateral globus pallidus. High-dose pulse glucocorticoid and rituximab were prescribed during her admission and the neuropsychiatric symptoms diminished upon treatment. No alternation in mental status or involuntary movements were noted at follow-up. Our patient was diagnosed with neuropsychiatric lupus, with clinical symptoms and image findings mimicking those of serotonin syndrome. Neuroimaging, such as MRI, detects various structural brain abnormalities and may provide pathophysiological evidence of clinical manifestations.
PubMed: 38930045
DOI: 10.3390/jcm13123516 -
Journal of Clinical Medicine Jun 2024The association between anti-Ro/SSA antibodies and the appearance of cardiac rhythm disorders in adults is discussed. We aim to study this relationship, together with...
The association between anti-Ro/SSA antibodies and the appearance of cardiac rhythm disorders in adults is discussed. We aim to study this relationship, together with active treatments and comorbidities, and its impact on daily clinical practice in adults with systemic autoimmune diseases (SADs). This cross-sectional single-center study was conducted in a tertiary hospital between January 2021 and March 2022. A sample of adult patients followed up in the SAD Unit with a diagnosis of a SAD and previously tested for anti-Ro/SSA and anti-La/SSB were recruited. All of them underwent a 12-lead electrocardiogram. 167 patients were included. 90 (53.9%) were positive for anti-Ro60, 101 (60.5%) for anti-Ro52, and 45 (26.9%) for anti-La/SSB; 52 (31.3%) were triple-negative. 84% were women, and the mean age was 59 years (standard deviation 12.8). The most common SAD was primary Sjögren's syndrome (34.8%), followed by systemic lupus erythematosus (24.6%) and rheumatoid arthritis (22.8%). A statistically significant relationship was found between anti-Ro52 positivity and cardiac rhythm disorders (relative risk = 2.007 [1.197-3.366]), specifically QTc prolongation (relative risk = 4.248 [1.553-11.615]). Multivariate regressions showed a significant association, with diabetes mellitus being the most related comorbidity. The association between anti-Ro52 antibodies and atrioventricular conduction disorders was not significant. The presence of anti-Ro52 antibodies in adult patients with SADs is associated with an increased risk of QTc prolongation. Electrocardiographic screening of patients with SAD, anti-Ro52 antibodies, and other risk factors, like diabetes mellitus or QT-prolonging drugs, seems advisable. Those with baseline electrocardiogram abnormalities or additional risk factors should undergo electrocardiographic monitoring.
PubMed: 38930039
DOI: 10.3390/jcm13123510 -
Journal of Clinical Medicine Jun 2024: To date, the literature concerning real-world data on the retention rate and safety of Janus kinase inhibitors (JAKis) is limited. To retrospectively evaluate the...
: To date, the literature concerning real-world data on the retention rate and safety of Janus kinase inhibitors (JAKis) is limited. To retrospectively evaluate the overall drug retention rate (DRR) of different JAKis in a monocentric cohort of patients with rheumatoid arthritis (RA). : Patients diagnosed with RA and treated with JAKis who were evaluated at our outpatient clinic from March 2017 to December 2023 were included in the study. Demographic, clinical characteristics, and comorbidities were recorded. The DRR was evaluated as the time to drug discontinuation, and baseline predictors of drug discontinuation were investigated through Cox regression after adjusting for baseline confounders. : The global DRR for JAKis was 51.3%. The DRR was 37.5% for tofacitinib, 46.6% for baricitinib, 69.4% for upadacitinib, and 53.5% for filgotinib. Considering all JAKis, the only significant predictor of drug discontinuation was the use of JAKis as a first-line treatment (HR 95% CI [0.25 (0.13-0.46)]. When considering each JAKi individually, a longer disease duration predicted TOF discontinuation (HR95% CI [1.05 (1.01-1.09)], while seropositivity protected against TOF being withdrawn (HR95% CI [0.41 (0.17-0.97)]. No independent predictors emerged for other JAKis. : the use of JAKis as a first-line treatment as well as disease duration and serology may impact the DRR of JAKis, which may inform tailored treatment strategies in clinical practice.
PubMed: 38930022
DOI: 10.3390/jcm13123494