Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial.
OBJECTIVE
To determine the effect of two different weekly doses of folic acid on the toxicity and efficacy of low-dose methotrexate therapy for rheumatoid arthritis.


METHODS
Randomized, double-blind, placebo-controlled study.


METHODS
79 persons between 19 and 78 years of age who fulfilled the American Rheumatism Association's criteria for rheumatoid arthritis.


METHODS
Participants were randomly assigned to visually identical placebo or to 5 mg or 27.5 mg of folic acid each week.


METHODS
Duration, intensity, and clinical severity of toxic events; efficacy (indices of joint tenderness and swelling and grip strength); plasma and erythrocyte folate levels; and other laboratory variables.


RESULTS
Folic acid supplementation at either dose did not affect the efficacy of methotrexate therapy as judged by joint indices and patient and physician assessments of disease. Patients given folic acid supplements had lower toxicity scores than did participants given placebo (P < or = 0.001). Low blood folate levels and increased mean corpuscular volumes were associated with substantial methotrexate toxicity, whereas daily dietary intakes of more than 900 nmol (400 micrograms) of folic acid were associated with little methotrexate toxicity.


CONCLUSIONS
Folic acid, an inexpensive vitamin, is safe in a broad range of doses and protects patients with rheumatoid arthritis who are taking methotrexate from toxicity while preserving the efficacy of methotrexate.
Birmingham Veteran's Administration Hospital, Alabama.
S L
SL
Morgan
J E
JE
Baggott
W H
WH
Vaughn
J S
JS
Austin
T A
TA
Veitch
J Y
JY
Lee
W J
WJ
Koopman
C L
CL
Krumdieck
G S
GS
Alarcón
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D004032:Diet; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D010352:Patient Dropouts; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000008:administration & dosage
D005492:Folic Acid; D014805:Vitamin B 12; D008727:Methotrexate