Weekly split‐dose regimen for oral methotrexate reduced polyglutamation in red blood cells in patients with rheumatoid arthritis compared with single‐dose regimen: Results from a multicentered randomized control trial

Nagaoka, Shinya; Katayama, Kou; Kasama, Tsuyoshi; Sato, Masao; Ohno, Shigeru; Amasaki, Yoshiharu; Kataoka, Hiroshi; Furusaki, Akira; Kon, Yujiro; Okamoto, Masahiro; Sasano, Minoru; Sagawa, Akira

doi:10.1111/1756-185x.13931

Cited by 2 publications

(1 citation statement)

References 25 publications

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“…32 Additionally, previous studies have reported the high incidence of medication error associated with the weekly dose of MTX. 14,20,21 Despite there are a few studies that modify the standard dosing method of MTX, [19][20][21]33 the current one evaluates daily administration of a low dose of MTX compared to an identical weekly dosage. Pandya et al found that in patients under weekly dosage scheme, remission was achieved after 4 weeks on treatment, with a decrease of the basal swollen joint count of (mean AE SD) 6.6 AE 6.6 to 4.10 AE 6.14; however, this response was not sustained in the follow-up.…”

Section: Discussionmentioning

confidence: 99%

Disease activity and therapeutic drug monitoring of polyglutamates of methotrexate after daily or weekly administration of low‐dose methotrexate in patients recently diagnosed with rheumatoid arthritis

Rodríguez-Báez

Huerta-García

Medellín‐Garibay

et al. 2022

Basic Clin Pharma Tox

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Low‐dose methotrexate can be challenging to treat rheumatoid arthritis due to side effects, lack of adherence and risk of medication errors. The aim of this study was to explore the safety and efficacy of low‐dose methotrexate administered daily or weekly in patients with rheumatoid arthritis. Patients were randomized according to a total oral dose of 12.5 mg of methotrexate administered: (A) divided in 5 days/week and (B) once per week. Patients were assessed along 24 weeks after starting treatment. Polyglutamates of methotrexate were quantified by ultrahigh‐performance liquid chromatography coupled to tandem mass spectrometer. Patients from groups A and B showed a good response to methotrexate treatment in 29% and 25.5%, respectively, and a global frequency of adverse events of 37%. Methotrexate polyglutamate 3 concentrations were higher in normal weight (body mass index 18.5–24.9 kg/m2) than in obese (body mass index 30 kg/m2) patients with a median (interquartile range) of 28 (17.95–45.15) and 10.35 (5.22–30.88) nM without differences between dosage groups. Daily dosage regimen represents a therapeutic alternative without compromising the efficacy and safety of methotrexate treatment and with similar adherence patterns than weekly dosage regimen; further, methotrexate polyglutamate 3 concentrations could be a useful tool for therapeutic drug monitoring purposes.

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Section: Discussionmentioning

confidence: 99%

Disease activity and therapeutic drug monitoring of polyglutamates of methotrexate after daily or weekly administration of low‐dose methotrexate in patients recently diagnosed with rheumatoid arthritis

Rodríguez-Báez

Huerta-García

Medellín‐Garibay

et al. 2022

Basic Clin Pharma Tox

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Oral Versus Subcutaneous Methotrexate in Immune-Mediated Inflammatory Disorders: an Update of the Current Literature

Vermeer,

Hebing,

van de Meeberg

et al. 2023

Curr Rheumatol Rep

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Purpose This review aims to critically evaluate the potential benefit of either oral or subcutaneous administration of methotrexate (MTX) in various immune-mediated inflammatory disorders (IMIDs) through analysis of efficacy, toxicity, pharmacokinetics and pharmacodynamics of both administration routes. Recent Findings Recent studies comparing the efficacy of oral versus subcutaneous MTX administration in IMIDs have revealed contradicting results. Some reported higher efficacy with subcutaneous administration, while others found no significant difference. Regarding toxicity, some studies have challenged the notion that subcutaneous administration is better tolerated than oral administration, while others have supported this. Pharmacokinetic studies suggest higher plasma bioavailability and increased accumulation of MTX-polyglutamates (MTX-PGs) in red blood cells (RBCs) with subcutaneous administration during the initial treatment phase. However, after several months, similar intracellular drug levels are observed with both administration routes. Summary There is no conclusive evidence supporting the superiority of either oral or subcutaneous MTX administration in terms of efficacy and adverse events in IMIDs. Subcutaneous administration leads to higher plasma bioavailability and initial accumulation of MTX-PGs in RBCs, but the difference seems to disappear over time. Given the variable findings, the choice of administration route may be based on shared decision-making, offering patients the option of either oral or subcutaneous administration of MTX based on individual preferences and tolerability. Further research is needed to better understand the impact of MTX-PGs in various blood cells and TDM on treatment response and adherence to MTX therapy.

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Weekly split‐dose regimen for oral methotrexate reduced polyglutamation in red blood cells in patients with rheumatoid arthritis compared with single‐dose regimen: Results from a multicentered randomized control trial

Cited by 2 publications

References 25 publications

Disease activity and therapeutic drug monitoring of polyglutamates of methotrexate after daily or weekly administration of low‐dose methotrexate in patients recently diagnosed with rheumatoid arthritis

Disease activity and therapeutic drug monitoring of polyglutamates of methotrexate after daily or weekly administration of low‐dose methotrexate in patients recently diagnosed with rheumatoid arthritis

Oral Versus Subcutaneous Methotrexate in Immune-Mediated Inflammatory Disorders: an Update of the Current Literature

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