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British Journal of Clinical Pharmacology Oct 2019Methotrexate at low doses (5-25 mg/week) is first-line therapy for rheumatoid arthritis. However, there is inter- and intrapatient variability in response, with... (Review)
Review
Methotrexate at low doses (5-25 mg/week) is first-line therapy for rheumatoid arthritis. However, there is inter- and intrapatient variability in response, with contribution of variability in concentrations of active polyglutamate metabolites, associated with clinical efficacy and toxicity. Prescribing remains heterogeneous across population groups, disease states and regimens. This review examines current knowledge of dose-response of oral methotrexate in the setting of rheumatoid arthritis, and how this could help inform dosage regimens.
Topics: Administration, Oral; Antirheumatic Agents; Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Humans; Methotrexate; Polyglutamic Acid; Practice Patterns, Physicians'
PubMed: 31276602
DOI: 10.1111/bcp.14057 -
Rheumatology (Oxford, England) Mar 2024Biologic and targeted synthetic DMARDs (b/tsDMARDs) have revolutionized the management of multiple rheumatic inflammatory conditions. Among these, polyarticular JIA... (Review)
Review
Biologic and targeted synthetic DMARDs (b/tsDMARDs) have revolutionized the management of multiple rheumatic inflammatory conditions. Among these, polyarticular JIA (pJIA) and RA display similarities in terms of disease pathophysiology and response pattern to b/tsDMARDs. Indeed, the therapeutic efficacy of novel targeted drugs is variable among individual patients, in both RA and pJIA. The mechanisms and determinants of this heterogeneous response are diverse and complex, such that the development of true 'precision'-medicine strategies has proven highly challenging. In this review, we will discuss pathophysiological, patient-specific, drug-specific and environmental factors contributing to individual therapeutic response in pJIA in comparison with what is known in RA. Although some biomarkers have been identified that stratify with respect to the likelihood of either therapeutic response or non-response, few have proved useful in clinical practice so far, likely due to the complexity of treatment-response mechanisms. Consequently, we propose a pragmatic, patient-centred and clinically based approach, i.e. personalized instead of biomarker-based precision medicine in JIA.
Topics: Adult; Humans; Arthritis; Precision Medicine; Inflammation; Antirheumatic Agents
PubMed: 37725352
DOI: 10.1093/rheumatology/kead490 -
RMD Open Mar 2021We summarised four pivotal Randomised Controlled Trials (RCTs) with antirheumatic drugs on the secondary prevention of cardiovascular events. The favourable effects of... (Review)
Review
We summarised four pivotal Randomised Controlled Trials (RCTs) with antirheumatic drugs on the secondary prevention of cardiovascular events. The favourable effects of canakinumab and colchicine confirm (low-grade) inflammation as an independent risk factor for cardiovascular events. While colchicine might be the first drug in the clinic, we expect that this is only the first in a future series of anti-inflammatory drugs used in secondary prevention of cardiovascular events.
Topics: Anti-Inflammatory Agents; Antirheumatic Agents; Cardiovascular Diseases; Colchicine; Humans; Inflammation
PubMed: 33727219
DOI: 10.1136/rmdopen-2020-001560 -
Frontiers in Immunology 2023Alterations in the composition or function of the gut microbiota are associated with the etiology of human diseases. Drug-microbiota interactions can affect drug... (Review)
Review
Alterations in the composition or function of the gut microbiota are associated with the etiology of human diseases. Drug-microbiota interactions can affect drug bioavailability, effectiveness, and toxicity through various routes. For instance, the direct effect of microbial enzymes on drugs can either boost or diminish their efficacy. Thus, considering its wide range of metabolic capabilities, the gut microbiota is a promising target for pharmacological modulation. Furthermore, drugs can alter the microbiota and the mechanisms by which they interact with their host. Individual variances in microbial profiles can also contribute to the different host responses to various drugs. However, the influence of interactions between the gut microbiota and drugs on treatment efficacy remains poorly elucidated. In this review, we will discuss the impact of microbiota dysbiosis in the pathogenesis of rheumatoid arthritis (RA), and we will attempt to elucidate the crosstalk between the gut microbiota and disease-modifying anti-rheumatic drugs (DMARDs), with an emphasis on how drug-microbiota interactions affect the treatment efficacy in RA. We speculate that improved knowledge of these critical interactions will facilitate the development of novel therapeutic options that use microbial markers for predicting or optimizing treatment outcomes.
Topics: Humans; Gastrointestinal Microbiome; Arthritis, Rheumatoid; Antirheumatic Agents; Microbiota; Treatment Outcome
PubMed: 37841256
DOI: 10.3389/fimmu.2023.1189036 -
Cells Apr 2022Autophagy is a lysosomal pathway for the degradation of damaged proteins and intracellular components that promotes cell survival under specific conditions. Apoptosis... (Review)
Review
Autophagy is a lysosomal pathway for the degradation of damaged proteins and intracellular components that promotes cell survival under specific conditions. Apoptosis is, in contrast, a critical programmed cell death mechanism, and the relationship between these two processes influences cell fate. Recent evidence suggests that autophagy and apoptosis are involved in the self-tolerance promotion and in the regulatory mechanisms contributing to disease susceptibility and immune regulation in rheumatic diseases. The aim of this review is to discuss how the balance between autophagy and apoptosis may be dysregulated in multiple rheumatic diseases and to dissect the role of autophagy in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome. Furthermore, to discuss the potential capacity of currently used disease-modifying antirheumatic drugs (DMARDs) to target and modulate autophagic processes.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Autophagy; Humans; Rheumatic Diseases; Sjogren's Syndrome
PubMed: 35456038
DOI: 10.3390/cells11081359 -
Advances in Therapy Sep 2020Caring for women in the postnatal period can be challenging. One of the most important aspects is ensuring disease control as there is a risk of flare in the postpartum... (Review)
Review
Caring for women in the postnatal period can be challenging. One of the most important aspects is ensuring disease control as there is a risk of flare in the postpartum period. Other aspects of care also need to be addressed with the mother in mind such as breastfeeding or with the neonate in mind such as vaccinations or complications of the maternal condition affecting the neonate. This article highlights aspects of care that need to be addressed in the postpartum period such as flare rates, maternal wellbeing, thromboembolism, vaccinations, contraception and breast feeding.
Topics: Adult; Aftercare; Antirheumatic Agents; Breast Feeding; Contraception; Female; Humans; Infant, Newborn; Postnatal Care; Postpartum Period; Pregnancy; Rheumatic Diseases; Risk Factors
PubMed: 32729009
DOI: 10.1007/s12325-020-01448-1 -
Seminars in Arthritis and Rheumatism Feb 2023This systematic review (SR) describes the efficacy and safety of biologic disease modifying anti-rheumatic drugs (bDMARDs) for patients with adult-onset Still's disease... (Review)
Review
This systematic review (SR) describes the efficacy and safety of biologic disease modifying anti-rheumatic drugs (bDMARDs) for patients with adult-onset Still's disease (AOSD). Three randomised controlled trials (RCTs), one retrospective case series of multiple interventions, and 17 case series of single interventions met the inclusion criteria for this SR. Comparisons of biologic therapy in AOSD were only available against conventional DMARDs in one RCT and against placebo in two RCTs. There was a lack of common assessment criteria, meaning treatment efficacy across studies could not be compared. Uncontrolled retrospective case series suggested that bDMARDs have an effect for patients with AOSD, but these studies did not provide comparative data to show whether bDMARDs were more effective than other interventions or, whether any bDMARD was more effective than another bDMARD. However, there was evidence that bDMARDs could reduce steroid dose. Safety data from all included studies showed that bDMARDs appear to be a safe alternative to conventional DMARDs. This SR has highlighted the need for larger comparative studies in AOSD and has shown the need to standardize the definition of therapeutic response in AOSD. This would allow comparisons between studies in order to gain clarity on which bDMARDs may be more effective treatments for AOSD.
Topics: Adult; Humans; Still's Disease, Adult-Onset; Antirheumatic Agents; Biological Factors; Treatment Outcome; Biological Products
PubMed: 36442231
DOI: 10.1016/j.semarthrit.2022.152139 -
Clinical and Experimental Rheumatology 2019A disease-modifying osteoarthritis drug (DMOAD) is a drug that modifies the underlying OA pathophysiology and potentially inhibits the structural damage to prevent or... (Review)
Review
A disease-modifying osteoarthritis drug (DMOAD) is a drug that modifies the underlying OA pathophysiology and potentially inhibits the structural damage to prevent or reduce long-term disability with potential symptomatic relief. The focus of this narrative review is on describing the state of the field for disease-modifying pharmacologic agents that are in late-stage development-specifically phase 2/3.
Topics: Antirheumatic Agents; Biological Products; Humans; Osteoarthritis
PubMed: 31621568
DOI: No ID Found -
British Journal of Clinical Pharmacology Oct 2019Available evidence indicates that a therapeutic drug monitoring strategy leads to major cost savings related to the anti-tumour necrosis factor-α therapy in both... (Review)
Review
Available evidence indicates that a therapeutic drug monitoring strategy leads to major cost savings related to the anti-tumour necrosis factor-α therapy in both inflammatory bowel disease and rheumatoid arthritis (RA) patients, with no negative impact on efficacy. However, although the systematic use of therapeutic drug monitoring could potentially be beneficial and economically acceptable to drug dose optimization, it is not justifiable for all drugs. Infliximab (IFX) is a chimeric monoclonal immunoglobulin G1 targeting tumour necrosis factor. It has been approved for the treatment of immuno-inflammatory diseases, including RA, ankylosing spondylitis, psoriatic arthritis, Crohn's disease and ulcerative colitis. IFX's pharmacokinetics is highly variable and influences clinical response in chronic inflammatory diseases. Clinical response increases with IFX trough concentrations in RA, ankylosing spondylitis, inflammatory bowel disease and psoriatic patients. Target concentrations predictive of good clinical response were proposed in RA, Crohn's disease and ulcerative colitis. The purpose of this article is to review the current literature surrounding IFX serum concentrations and their related parameters with disease activity in patients with spondyloarthritis. Gathering information about the efficacy of IFX in patients with spondyloarthritis and relating IFX serum concentrations to disease activity were the main goals of this study.
Topics: Antirheumatic Agents; Drug Monitoring; Humans; Infliximab; Spondylarthritis; Tumor Necrosis Factor-alpha
PubMed: 31315147
DOI: 10.1111/bcp.14062 -
Frontiers in Immunology 2023There is an increased risk of malignancies in patients with many systemic rheumatic diseases, which negatively impact on their quality of life. The risk and types of... (Review)
Review
There is an increased risk of malignancies in patients with many systemic rheumatic diseases, which negatively impact on their quality of life. The risk and types of malignancies can differ by the type of rheumatic diseases. Possible mechanisms linking them are dynamic and complicated, including chronic inflammation and damage in rheumatic disease, inability to clear oncogenic infections, shared etiology and some anti-rheumatic therapies. Although certain disease-modifying anti-rheumatic drugs (DMARDs) have been proved to be potentially carcinogenic, the majority of them were not associated with increased risk of most malignancies in patients with systemic rheumatic diseases.
Topics: Humans; Quality of Life; Rheumatic Diseases; Antirheumatic Agents; Inflammation; Neoplasms
PubMed: 36926334
DOI: 10.3389/fimmu.2023.1095526