PROSPECTIVELY MEASURED RED-CELL FOLATE LEVELS IN METHOTREXATE-TREATEDPATIENTS WITH RHEUMATOID-ARTHRITIS - RELATION TO WITHDRAWAL AND SIDE-EFFECTS

Objective. To investigate whether red cell relate (RCF) levels relate to side effects, withdrawals, or disease activity during treatment wit h the folic acid antagonist methotrexate (MTX) for rheumatoid arthriti s (RA), Methods. Side effects were recorded monthly, RCF levels were m easured by lactoglobulin binding radioassays, and 8 variables for dise ase activity were measured in a placebo controlled double blind trial of 28 weeks' duration comparing efficacy of MTX (n = 23) and D-penicil lamine (n = 23), Results, From Week 20 RCF levels decreased only in th e MTX group (p < 0.02), and 5 MTX treated patients withdrew due to sid e effects, Withdrawals had lower RCF values at Weeks 0 and 9 compared to the remaining patients (p < 0.05), Folate deficiency evolved in 5 p atients: 2 of these developed cytopenia. Aberrations in the scheduled dosage increase were related to levier pretreatment values of RCF (p = 0.007). Side effect scores were inversely correlated to RCF values at Weeks 0, 9, and 28 (p < 0.05), RCF levels measured concomitantly with liver enzyme elevation were lower than the remaining values (p < 0.00 1), When side effects were reported, 96% of concomitantly measured RCF values were below SOD nmol/l. RCF values at entry did not correlate t o improvement in any variable for disease activity, or a graded overal l improvement. Conclusion. RCF levels decrease during MTX treatment an d relate to side effects, withdrawals, liver enzyme elevations and abe rrant MTX dosage increase, but not to the therapeutic effect, RCF abov e 800 nmol/l protects against side effects.