Resistance to methotrexate and other rheumatic drugs

Heijden of the Netherlands, etc., suggested that resistance to rheumatoid drugs (DMARD) used in rheumatoid arthritis treatments could lead to poor treatment or treatment failure(Nat Clin Pract Rheumatol 2007, 3:26)At present, as one of the reasons for the failure of treatment, drug resistance has received sufficient attention in the treatment oftumorand anti-infection, but has just been recognized in the treatment of rheumatoid arthritisThe authors suggest that an important phenomenon in the application of DMARD to rheumatoid arthritis is that the efficacy of the drug will gradually declineThe root cause of the failure of anti-rheumatic drugs is not yet fully understood, but it may or may be mediated in part by cell resistanceCell resistance can be divided into two types: primary and secondary resistanceSecondary drug resistance refers to the drug resistance that the cells were originally sensitive to but occurred during treatmentIn the treatment of rheumatoid arthritis, a study by Morgan et alshowed that 5% to 10% of rheumatoid arthritis patients were resistant to DMARDPossible drug resistance mechanisms include impaired drug-to-target cell delivery, drug intake disorders, increased drug discharge, changes in intracellular drug activity, inhibition of active targets, or moreThe discharge of a large number of drugs is an important mechanism of drug resistanceAt present, the study is more clear is the drug resistance mechanism of methotrexate, that is, due to the expression of carrier protein on the cell membrane reduced or transshipment energy changes, resulting in methotrexate intake of cells and reduced concentration of drugs in the cell, thereby affecting the efficacy of the drugIn addition, methotrexate in cells is converted into the form of polyglutamate salts is also a reason for drug resistanceThe possible mechanism of drug resistance in lyuniating sulphate is an increase in drug dischargeRheumatoid arthritis takes a long time to take medication, and maintaining the efficacy of anti-rheumatoid drugs is a challenge Increasing the dose of the drug only may restore the effect, but it may also increase the side effects of the drug and lead to the interruption of treatment