The feasibility and pharmacokinetic study of using loading dose methotrexate in rheumatoid arthritis patients. - Trial ANZCTR12623000420640

Timeline & Enrollment

Primary Outcome

Pharmacokinetic of methotrexate polyglutamate inside the red blood cell: the pharmacokinetic parameters for methotrexate polyglutamates inside red blood cell will be calculated via the Monolix software. The parameters for each polyglutamate (eg MTX-Glu1, MTX-Glu2 etc..) will be calculated individually, and also modelled together using multi-compartmental analysis. The parameters of interest will be steady state concentration, half-life, clearance, time to steady state (defined as 90% of the steady state concentration), area under the concentration time curve and time to detection of methotrexate polyglutamates in red blood cell. ;; Tolerance to, and safety of triple DMARD therapy that includes a methotrexate loading dose for initial treatment of RA. The patients will be presented with a list of possible side effects (such as upper and lower GI, rash, shortness of breath etc.) in the Vital Activities and Lifestyle Index (VALI) Follow-up form. The patients will be asked to tick any side effect that they experienced with the dosing. Further assessment and review regarding the severity of side effect will be performed in the consultation process. The incidence and severity of Adverse Events (AEs)/Serious Adverse Events (SAEs) will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (Version 5). Any change from baseline in physical examination findings, and from baseline in vital signs (Blood pressure and heart rate measured using a sphygmomanometer, respiratory rate using manual breath count and temperature by tympanic thermometer) will also be recorded.

Summary

Loading doses of methotrexate (where high dose methotrexate injection is given once weekly for three weeks at the start to control the disease activity of rheumatoid arthritis, followed by lower dose of oral methotrexate as maintenance) have been used sporadically by rheumatologists in practice, but the research evidence for the loading dose of methotrexate is limited. This study is aimed to investigate how the concentration of methotrexate and its active metabolites differ compared to the standard dose regimen. Also, this study is also aimed to assess the feasibility to implement this loading dose regimen in real life, and the patient's attitude towards this new dosing regimen.

ICD-10 Classifications