Prospectively measured red cell folate levels in methotrexate treated patients with rheumatoid arthritis: relation to withdrawal and side effects.
OBJECTIVE
To investigate whether red cell folate (RCF) levels relate to side effects, withdrawals, or disease activity during treatment with the folic acid antagonist methotrexate (MTX) for rheumatoid arthritis (RA).


METHODS
Side effects were recorded monthly, RCF levels were measured by lactoglobulin binding radioassays, and 8 variables for disease activity were measured in a placebo controlled double blind trial of 28 weeks' duration comparing efficacy of MTX (n = 23) and D-penicillamine (n = 23).


RESULTS
From Week 20 RCF levels decreased only in the MTX group (p < 0.02), and 5 MTX treated patients withdrew due to side effects. Withdrawals had lower RCF values at Weeks 0 and 9 compared to the remaining patients (p < 0.05). Folate deficiency evolved in 5 patients; 2 of these developed cytopenia. Aberrations in the scheduled dosage increase were related to lower 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 < 0.001). When side effects were reported, 96% of concomitantly measured RCF values were below 800 nmol/l. RCF values at entry did not correlate to improvement in any variable for disease activity, or a graded overall improvement.


CONCLUSIONS
RCF levels decrease during MTX treatment and relate to side effects, withdrawals, liver enzyme elevations and aberrant MTX dosage increase, but not to the therapeutic effect. RCF above 800 nmol/l protects against side effects.
Andersen
L S
LS
Department of Rheumatology, King Christian X Hospital, Gråsten, Denmark.
Hansen
E L
EL
Knudsen
J B
JB
Wester
J U
JU
Hansen
G V
GV
Hansen
T M
TM
D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004912:Erythrocytes / Q000737:chemistry* / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000032:analysis*; D005494:Folic Acid Deficiency / Q000139:chemically induced; D006801:Humans; D007782:Lactoglobulins / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D011446:Prospective Studies; D011869:Radioligand Assay; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D018501:Antirheumatic Agents; D007782:Lactoglobulins; D005492:Folic Acid; D008727:Methotrexate