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 Article uri icon

abstract

  • 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%25 and 25.5%25, respectively, and a global frequency of adverse events of 37%25. 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. © 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley %26 Sons Ltd.
  • 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%25 and 25.5%25, respectively, and a global frequency of adverse events of 37%25. 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. © 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.

publication date

  • 2022-01-01