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CMAJ : Canadian Medical Association... Jan 2021
Topics: Female; Hand; Humans; Methotrexate; Middle Aged; Psoriasis
PubMed: 33667188
DOI: 10.1503/cmaj.200517-f -
Pharmacological Reports : PR 2006A variety of disease-modifying antirheumatic drugs (DMARDs) are available to control the clinical activity of rheumatoid arthritis (RA). Methotrexate (MTX), an analogue... (Review)
Review
A variety of disease-modifying antirheumatic drugs (DMARDs) are available to control the clinical activity of rheumatoid arthritis (RA). Methotrexate (MTX), an analogue of folic acid and of aminopterin, is the most commonly used DMARD and is now prescribed worldwide to at least 500,000 patients with RA. The mechanism by which MTX used at a low dose modulates inflammation in RA is still unknown. Monitoring of the therapy in terms of MTX concentration in patients with RA seems not to have a significant influence on the effectiveness of the treatment. Two meta-analyses showed that MTX has one of the best efficacy/toxicity ratios. It should be the first DMARD used in the majority of patients with RA at this time. However, a significant number of patients treated only with MTX fail to achieve optimal disease control, so there are many combinations of DMARD regimes. It is hoped that more aggressive use of conventional DMARDs and biological agents will result in less disability and a higher proportion of patients achieving remission. The therapy of RA is a dynamic process and requires maintaining a delicate balance between benefits and risks. Even with the newer biological agents, MTX continues to serve as a reference point and there is still a role for MTX in the treatment of RA patients.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Humans; Meta-Analysis as Topic; Methotrexate; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 16963793
DOI: No ID Found -
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 -
The Journal of Dermatological Treatment Dec 2024Methotrexate is an off-label therapy for atopic dermatitis. A lack of consensus on dosing regimens poses a risk of underdosing and ineffective treatment or overdosing... (Review)
Review
Methotrexate is an off-label therapy for atopic dermatitis. A lack of consensus on dosing regimens poses a risk of underdosing and ineffective treatment or overdosing and increased risk of side effects. This systematic review summarizes the available evidence on dosing regimens.A literature search was conducted, screening all randomized controlled trials (RCTs) and guidelines published up to 6 July 2023, in the MEDLINE, Embase, and Cochrane Library databases.Five RCTs and 21 guidelines were included. RCTs compared methotrexate with other treatments rather than different methotrexate dosing regimens. The start and maintenance doses in RCTs varied between 7.5-15 mg/week and 14.5-25 mg/week, respectively. Despite varied dosing, all RCTs demonstrated efficacy in improving atopic dermatitis signs and symptoms. Guidelines exhibited substantial heterogeneity but predominantly proposed starting doses of 5-15 mg/week for adults and 10-15 mg/m/week for children. Maintenance doses suggested were 7.5-25 mg/week for adults and 0.2-0.7 mg/kg/week for children. One guideline suggested a test dose and nearly half advised folic acid supplementation.This systematic review highlights the lack of methotrexate dosing guidelines for atopic dermatitis. It identifies commonly recommended and utilized dosing regimens, serving as a valuable resource for clinicians prescribing methotrexate off-label and providing input for an upcoming consensus study.
Topics: Adult; Child; Humans; Methotrexate; Dermatitis, Atopic
PubMed: 38124505
DOI: 10.1080/09546634.2023.2292962 -
CMAJ : Canadian Medical Association... Jul 1987
Topics: Breast Neoplasms; Drug Hypersensitivity; Female; Humans; Methotrexate
PubMed: 3594340
DOI: No ID Found -
Journal of the American Chemical Society Nov 2018The efficacy and tolerability of systemically administered anticancer agents are limited by their off-target effects. Precise spatiotemporal control over their cytotoxic...
The efficacy and tolerability of systemically administered anticancer agents are limited by their off-target effects. Precise spatiotemporal control over their cytotoxic activity would allow improving chemotherapy treatments, and light-regulated drugs are well suited to this purpose. We have developed phototrexate, the first photoswitchable inhibitor of the human dihydrofolate reductase (DHFR), as a photochromic analogue of methotrexate, a widely prescribed chemotherapeutic drug to treat cancer and psoriasis. Quantification of the light-regulated DHFR enzymatic activity, cell proliferation, and in vivo effects in zebrafish show that phototrexate behaves as a potent antifolate in its photoactivated cis configuration and that it is nearly inactive in its dark-relaxed trans form. Thus, phototrexate constitutes a proof-of-concept to design light-regulated cytotoxic small molecules and a step forward to develop targeted anticancer photochemotherapies with localized efficacy and reduced adverse effects.
Topics: Animals; Antineoplastic Agents; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Humans; Methotrexate; Models, Molecular; Molecular Structure; Photochemical Processes; Photochemotherapy; Structure-Activity Relationship; Tetrahydrofolate Dehydrogenase; Zebrafish
PubMed: 30346152
DOI: 10.1021/jacs.8b08249 -
Clinical Chemistry and Laboratory... Mar 2021
Topics: Administration, Oral; Crystallization; Humans; Male; Methotrexate; Middle Aged; Urinary Calculi
PubMed: 33090966
DOI: 10.1515/cclm-2020-1268 -
Inflammatory Bowel Diseases Aug 2010Low-dose methotrexate is a widely used and efficacious therapy in chronic inflammatory disorders such as psoriasis and rheumatoid arthritis. Prospective randomized... (Review)
Review
BACKGROUND
Low-dose methotrexate is a widely used and efficacious therapy in chronic inflammatory disorders such as psoriasis and rheumatoid arthritis. Prospective randomized controlled trials have demonstrated the efficacy of parenteral methotrexate in Crohn's disease (CD). We performed a systematic review of the efficacy of methotrexate in ulcerative colitis (UC) and discuss the results in the context of the known pharmacokinetics and adverse events of methotrexate therapy in inflammatory bowel diseases and other inflammatory conditions.
MATERIALS AND METHODS
We performed a systematic review of the literature in Medline, Embase, and Web of Science. All publications describing patients with UC treated with methotrexate were included.
RESULTS
We identified 12 studies or retrospective case series and 5 meeting abstracts that met the inclusion criteria. Only 1 study reported a prospective randomized placebo-controlled trial using methotrexate at a dose of 12.5 mg orally with no significant clinical benefit. However, the majority of uncontrolled retrospective analyses suggest a clinical response to methotrexate therapy in a range of 30%-80% when the drug is applied by parenteral route in doses between 20-25 mg.
CONCLUSIONS
The only randomized controlled trial of methotrexate in UC employed oral dosing and doses lower than those shown to be effective in CD and did not demonstrate efficacy, whereas uncontrolled, retrospective studies using doses and routes of administration similar to those employed in CD suggest benefit. Well-designed, prospective, placebo-controlled trials of methotrexate in UC are needed.
Topics: Colitis, Ulcerative; Female; Folic Acid Antagonists; Humans; Male; Methotrexate; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome
PubMed: 20186931
DOI: 10.1002/ibd.21246 -
Arthritis & Rheumatology (Hoboken, N.J.) May 2017
Topics: Arthritis, Rheumatoid; Humans; Methotrexate
PubMed: 28217918
DOI: 10.1002/art.40061 -
Advanced Science (Weinheim,... Jul 2022The continual growth of tumor cells requires considerable nutrient consumption. Methotrexate (MTX) is used to treat certain types of cancer by blocking the DNA and RNA...
The continual growth of tumor cells requires considerable nutrient consumption. Methotrexate (MTX) is used to treat certain types of cancer by blocking the DNA and RNA productions through interfering one-carbon metabolism and de novo purine and pyrimidine synthesis. However, treatment of MTX may cause many serious adverse effects, which hamper its clinical application. Herein, the authors synthesize ferrous ions, histidine, and MTX assembled nanoparticles (FHM) to deliver MTX at tumor site and enhance the sensitivity of tumor cells to MTX with histidine catabolism. Furthermore, fasting-mimicking diet (FMD) is applied to intervene in the one-carbon metabolism and enhance the cytotoxicity of MTX. Meanwhile, FMD treatment can significantly augment the cellular uptake and tumor accumulation of FHM nanoparticles. Due to the triple inhibitions of the one-carbon metabolism, the proliferation of tumor cells is strongly disturbed, as which is highly replying on DNA and RNA production. Taken together, a 95% lower dose of MTX adopted in combined therapy significantly inhibits the growth of two types of murine tumors without evident systemic toxicity. This strategy may provide a promising nucleotide metabolism-based nanomedicine for cancer therapy.
Topics: Animals; Carbon; DNA; Histidine; Humans; Methotrexate; Mice; Nanoparticles; Neoplasms; Nucleotides; Nutrients; RNA
PubMed: 35508896
DOI: 10.1002/advs.202200482