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Expert Review of Clinical Immunology Mar 2024Atopic dermatitis is a prevalent skin condition causing dry, pruritic, inflammatory skin lesions that can result in patient distress. Various emerging classes of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Atopic dermatitis is a prevalent skin condition causing dry, pruritic, inflammatory skin lesions that can result in patient distress. Various emerging classes of therapy, including biologics and Janus kinase inhibitors, have been developed in recent years.
AREAS COVERED
A literature search of PubMed was conducted to explore existing literature and clinical trials. Treatment options and adverse effects were summarized by class and severity. JAK inhibitors and biologics are efficacious options for adults with severe atopic dermatitis. Using the Eczema Area and Severity Index (EASI) from 11 randomized control trials, the highest efficacy was seen with upadacitinib 30 mg with 70% of patients achieving EASI-75. Older, immune-inhibiting treatment options are still appropriate options to improve patient conditions. A meta-analysis of 39 randomized control trials concluded high dose cyclosporine is more effective at improving quality of life and itch when compared to azathioprine and methotrexate. Newly developed topical and systemic medications improve disease and itch severity and can be considered in patients without adequate control with their initial treatment regimen. Adverse effects must be considered when using the newer options, although major adverse events were not seen.
EXPERT OPINION
Current management options are efficacious, but adherence is required for any effect.
Topics: Adult; Humans; Dermatitis, Atopic; Quality of Life; Cyclosporine; Methotrexate; Biological Products; Treatment Outcome; Severity of Illness Index
PubMed: 38037822
DOI: 10.1080/1744666X.2023.2291038 -
Clinical Oral Implants Research Sep 2023To review the current evidence on the relationship between agents that affect bone homeostasis and dental implant failures. (Review)
Review
OBJECTIVES
To review the current evidence on the relationship between agents that affect bone homeostasis and dental implant failures.
MATERIALS AND METHODS
Electronic searches for bisphosphonates, denosumab, methotrexate, corticosteroids, romosozumab, sunitinib, and bevacizumab were performed using PubMed, MEDLINE (OVID), EMBASE (OVID), Cochrane Central Register of Controlled Trials (Cochrane Library), Cochrane Oral Health Group Trials Register (Cochrane Library) and Web of Science (Thomson Reuters). Manual searches were also conducted to complement the digital searches for recent issues.
RESULTS
Previous publications suggested that bisphosphonates do not compromise the survival of dental implants. However, one study documented an increased risk of implant failure in patients who had received high-dose of intravenous bisphosphonate therapy after implant rehabilitation. There has been an issue of MRONJ around implants in patients who have successfully received implant therapy before and after antiresorptive therapy, leading to late implant failure. Despite evidence on the detrimental effects of denosumab, methotrexate and corticosteroids on bone metabolism, their role in implant survival is not conclusive.
CONCLUSIONS
At present, there is insufficient evidence to establish a potential connection between agents that affects bone homeostasis and implant failure. However, some studies have reported negative results for implant therapy. In addition, implant-related sequestration in patients who received anti-resorptive therapy, despite of successful osseointegration, is also noticeable. Although limited studies are available at present, clinicians should still carefully consider the potential hazards and take appropriate precautions to minimize the risks associated with the medications and implant therapy.
Topics: Humans; Denosumab; Methotrexate; Homeostasis; Diphosphonates
PubMed: 37750523
DOI: 10.1111/clr.14144 -
Expert Opinion on Drug Metabolism &... Apr 2024High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to...
INTRODUCTION
High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to identify early risk factors associated with HDMTX-induced toxicities, paving the way for personalized treatment.
AREAS COVERED
A systematic review of PubMed and Cochrane databases was conducted for articles from inception to July 2023. Eligible studies included reviews, clinical trials, and real-world analyses. Irrelevant studies were excluded, and manual searches and citation reviews were performed. Factors such as MTX exposure, drug interactions, demographics, serum albumin, urine pH, serum calcium, and genetic polymorphisms affecting MTX transport (e.g. SLCO1B1), intracellular folate metabolism (MTHFR), cell development (ARID5B), metabolic pathways (UGT1A1, PNPLA3), as well as epigenetics were identified.
EXPERT OPINION
This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.
Topics: Humans; Antimetabolites, Antineoplastic; Dose-Response Relationship, Drug; Drug Interactions; Hematologic Neoplasms; Methotrexate; Polymorphism, Genetic; Precision Medicine; Risk Factors
PubMed: 38501267
DOI: 10.1080/17425255.2024.2332366 -
Journal of the European Academy of... Jan 2024Treating atopic dermatitis (AD) in pregnant or breastfeeding women, and in women and men with AD aspiring to be parents is difficult and characterized by uncertainty, as... (Review)
Review
Treating atopic dermatitis (AD) in pregnant or breastfeeding women, and in women and men with AD aspiring to be parents is difficult and characterized by uncertainty, as evidence to inform decision-making on systemic anti-inflammatory treatment is limited. This project mapped consensus across dermatologists, obstetricians and patients in Northwestern Europe to build practical advice for managing AD with systemic anti-inflammatory treatment in men and women of reproductive age. Twenty-one individuals (sixteen dermatologists, two obstetricians and three patients) participated in a two-round Delphi process. Full consensus was reached on 32 statements, partial consensus on four statements and no consensus on four statements. Cyclosporine A was the first-choice long-term systemic AD treatment for women preconception, during pregnancy and when breastfeeding, with short-course prednisolone for flare management. No consensus was reached on second-choice systemics preconception or during pregnancy, although during breastfeeding dupilumab and azathioprine were deemed suitable. It may be appropriate to discuss continuing an existing systemic AD medication with a woman if it provides good disease control and its benefits in pregnancy outweigh its risks. Janus kinase (JAK) inhibitors, methotrexate and mycophenolate mofetil should be avoided by women during preconception, pregnancy and breastfeeding, with medication-specific washout periods advised. For men preconception: cyclosporine A, azathioprine, dupilumab and corticosteroids are appropriate; a 3-month washout prior to conception is desirable for methotrexate and mycophenolate mofetil; there was no consensus on JAK inhibitors. Patient and clinician education on appropriate (and inappropriate) AD treatments for use in pregnancy is vital. A shared-care framework for interdisciplinary management of AD patients is advocated and outlined. This consensus provides interdisciplinary clinical guidance to clinicians who care for patients with AD before, during and after pregnancy. While systemic AD medications are used uncommonly in this patient group, considerations in this article may help patients with severe refractory AD.
Topics: Pregnancy; Male; Humans; Female; Cyclosporine; Methotrexate; Breast Feeding; Dermatitis, Atopic; Azathioprine; Mycophenolic Acid; Consensus; Anti-Inflammatory Agents
PubMed: 37818828
DOI: 10.1111/jdv.19512 -
Clinical and Experimental Rheumatology May 2024We investigated the effectiveness and safety of filgotinib in a real-life multicentre cohort of rheumatoid arthritis (RA) patients. (Observational Study)
Observational Study
OBJECTIVES
We investigated the effectiveness and safety of filgotinib in a real-life multicentre cohort of rheumatoid arthritis (RA) patients.
METHODS
RA patients were evaluated at baseline and after 12 and 24 weeks and were stratified based on previous treatments as biologic disease-modifying anti-rheumatic drug (bDMARD)-naive and bDMARD-insufficient responders (IR). Concomitant usage of methotrexate (MTX) and oral glucocorticoids (GC) was recorded. At each timepoint we recorded disease activity, laboratory parameters and adverse events.
RESULTS
126 patients were enrolled. 15.8% were bDMARD-naive (G0), while 84% were bDMARD-IR (G1). In G0, 45% of patients were in monotherapy (G2) and 55% were taken MTX (G3). In G1, 50% of patients were in monotherapy (G4) and 50% used MTX (G5).A significant reduction in all parameters at 12 weeks was observed; in the extension to 24 weeks the significant reduction was maintained for patient global assessment (PGA), examiner global assessment (EGA), visual analogue scale (VAS) pain, VAS fatigue, disease activity score (DAS)28- C-reactive protein (CRP) and CRP values. Filgotinib in monotherapy showed better outcomes in bDMARD-naive patients, with significant differences for patient reported outcomes (PROs) and DAS28-CRP. At 12 weeks, low disease activity (LDA) and remission were achieved in a percentage of 37.2 % and 10.7 % by simplified disease activity index (SDAI), 42.6 % and 5.7 % by clinical disease activity index (CDAI), 26.8 % and 25.2 % by DAS28-CRP, respectively. A significant decrease in steroid dose was evidenced in all patients. We observed a major adverse cardiovascular event in one patient and an increase in transaminase in another. No infections from Herpes Zoster were reported.
CONCLUSIONS
Our real-world data confirm the effectiveness and safety of filgotinib in the management of RA, especially in bDMARD-naive patients.
Topics: Humans; Arthritis, Rheumatoid; Male; Female; Middle Aged; Antirheumatic Agents; Treatment Outcome; Aged; Methotrexate; Adult; Drug Therapy, Combination; Triazoles; Remission Induction; Severity of Illness Index; Time Factors; Glucocorticoids; Protein Kinase Inhibitors
PubMed: 38197190
DOI: 10.55563/clinexprheumatol/k78ug3 -
Clinical Rheumatology Dec 2023Rheumatoid arthritis is a systemic disease characterized by progressive chronic inflammation resulting in destruction of synovial joints. In addition to joint...
OBJECTIVE
Rheumatoid arthritis is a systemic disease characterized by progressive chronic inflammation resulting in destruction of synovial joints. In addition to joint involvement, abnormal blood lipid indexes have also been found in RA patients. The correlation between various blood lipid indexes and the treatment effects were assessed in patients with rheumatoid arthritis, for the purposes to find a better medication strategy for RA.
METHODS
One hundred nineteen rheumatoid arthritis patients were recruited and divided into two groups, 45 patients with significant drug treatment effect and 45 patients with insignificant drug treatment effect through the nearest neighbor matching method in propensity score. The correlation between various blood lipid indexes and drug treatment effect of rheumatoid arthritis patients was analyzed. A mouse model of rheumatoid arthritis was constructed in the laboratory; methotrexate was treated as a positive drug. We observe and record the onset of rheumatoid arthritis in mice, as well as the proportion of immune cells, the expression of inflammatory factors, and the changes in blood lipid profiles was done.
RESULTS
The levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), and erythrocyte sedimentation rate (ESR) in rheumatoid arthritis patients were significantly different between the two groups (P < 0.05). There was no significant difference in other indexes between the two groups (P > 0.05). Methotrexate had a good therapeutic effect on CIA model mice, and the levels of TC and HDL-C in the treatment group were higher than those in the model group.
CONCLUSION
There is a high correlation between the levels of TC and HDL-C in rheumatoid arthritis patients and the effect of drug treatment. In the clinical treatment of rheumatoid arthritis, we should focus on improving the blood lipid indexes such as TC and HDL-C, and explore more targeted individualized administration, so as to achieve better and faster treatment effect in patients with rheumatoid arthritis. Key Points • In this research, we found that the TC and HDL-C level in RA patients' blood is highly related with the therapeutic effect, and a lower level of TC and HDL-C is better for therapeutic effect of RA.
Topics: Humans; Animals; Mice; Methotrexate; Retrospective Studies; Arthritis, Rheumatoid; Lipids; Lipoproteins, HDL; Treatment Outcome; Cholesterol, HDL
PubMed: 37488372
DOI: 10.1007/s10067-023-06683-9 -
Journal of the European Academy of... Nov 2023
Review
Topics: Humans; Methotrexate; Vitiligo; Retrospective Studies; Hypopigmentation; Treatment Outcome
PubMed: 37571807
DOI: 10.1111/jdv.19400 -
The British Journal of Dermatology Aug 2023
Topics: Humans; Methotrexate; Adalimumab; Biological Products; Cohort Studies; Dermatologists; Psoriasis; Immunologic Factors; Adjuvants, Immunologic
PubMed: 37421659
DOI: 10.1093/bjd/ljad231 -
Current Opinion in Rheumatology May 2024This review discusses updates in the prediction and prevention of future rheumatoid arthritis (RA). (Review)
Review
PURPOSE OF REVIEW
This review discusses updates in the prediction and prevention of future rheumatoid arthritis (RA).
RECENT FINDINGS
In individuals with musculoskeletal symptoms and elevated antibodies to citrullinated proteins (ACPA) without clinical inflammatory arthritis (IA), a 'simple' score has a positive predictive value (PPV) of ∼28% for clinical IA/RA within 1 year, and a comprehensive score (including ultrasound) has a PPV of ∼71% for clinical RA within 5 years. Controlled clinical trials in individuals at-risk for future RA have been performed using corticosteroids, rituximab, atorvastatin, methotrexate, hydroxychloroquine and abatacept. Abatacept modestly reduced rates of incident clinical RA and imaging inflammation within the trials, rituximab delayed clinical IA, and methotrexate improved function, symptoms and imaging inflammation. Vitamin D with or without omega 3 fatty acids reduced incidence of autoimmune diseases, including RA. While not proven in controlled clinical trials, observational studies suggest exercise, weight loss and smoking cessation may reduce progression to clinical RA.
SUMMARY
Prediction and prevention of RA is advancing although there are no currently approved interventions for prevention. Future studies should include deeper evaluation of the pathophysiology of RA development to improve prediction and identify key pathways to target in future clinical trials, as well as develop infrastructure to support prevention-related research.
Topics: Humans; Methotrexate; Abatacept; Rituximab; Arthritis, Rheumatoid; Inflammation
PubMed: 38441488
DOI: 10.1097/BOR.0000000000001013 -
BMC Complementary Medicine and Therapies Oct 2023Methotrexate (MTX) is a common chemotherapeutic drug that inhibits DNA synthesis and induces apoptosis. Treatment with MTX increased CD73 expression, which leads to...
BACKGROUND
Methotrexate (MTX) is a common chemotherapeutic drug that inhibits DNA synthesis and induces apoptosis. Treatment with MTX increased CD73 expression, which leads to higher levels of extracellular adenosine. Adenosine levels are also high in the tumor microenvironment through Cancer cells metabolism. That promotes the survival of cancer cells and contributes to tumor immune evasion through the Adenosine 2a Receptor. A2A receptor antagonists are an emerging class of agents that treat cancers by enhancing immunotherapy, both as monotherapy and in combination with other therapeutic agents. Caffeine is an adenosine receptor antagonist. Herein, we demonstrate the ability of a novel well prepared and characterized nano formula CAF-FA-CS-NPs (D4) for A2aR blockade when combination with MTX to improve its antitumor efficacy by enhancing the immune system and eliminating immune suppression.
METHODS
CAF-FA-CS-NPs (D4) were prepared and characterized for particle size, loading efficiency, and release profile. Molecular docking was used to validate the binding affinity of caffeine and folic acid to A2A receptor. The effects of the nano formula were evaluated on human liver cancer cells (HepG2), breast cancer cells (MCF-7), and MDA-MB-231, as well as normal human cells (WI-38). Different combination ratios of MTX and D4 were studied to identify the optimal combination for further genetic studies.
RESULTS
Molecular docking results validated that caffeine and folic acid have binding affinity to A2A receptor. The CS-NPs were successfully prepared using ionic gelation method, with caffeine and folic acid being loaded and conjugated to the nanoparticles through electrostatic interactions. The CAF loading capacity in D4 was 77.9 ± 4.37% with an encapsulation efficiency of 98.5 ± 0.37. The particle size was optimized through ratio variations. The resulting nanoparticles were fully characterized. The results showed that (D4) had antioxidant activity and cytotoxicity against different cancer cells. The combination of D4 with MTX (IC50 D4 + 0.5 IC50 MTX) resulted in the downregulation of Bcl-2, FOXP3, CD39, and CD73 gene expression levels and upregulation of Bax and A2AR gene expression levels in HepG2 cells.
CONCLUSIONS
This study suggests that CAF-FA-CS-NPs (D4) in combination with MTX may be a promising candidate for cancer immunotherapy, by inhibiting A2aR signaling and leading to improved immune activation and anti-tumor activity of MTX.
Topics: Humans; Methotrexate; Folic Acid; Chitosan; Receptor, Adenosine A2A; Caffeine; Molecular Docking Simulation; Neoplasms; Nanoparticles; Immunotherapy; Adenosine; Tumor Microenvironment
PubMed: 37891562
DOI: 10.1186/s12906-023-04212-4