Friday, August 10, 2001

Folate Lowers Toxicity of Arthritis Drug

NEW YORK (Reuters Health) - Patients taking a drug commonly prescribed for rheumatoid arthritis can lower their risk for drug-related liver damage by taking folate supplements, researchers report.

- 2001/08/10

The investigators found that patients who took folic acid or folinic acid supplements along with the arthritis drug methotrexate were less likely to have a malfunctioning liver than those taking just methotrexate. As a result, patients taking the folate supplements were able to continue their drug therapy for longer periods. The folate supplements did not affect the incidence, severity and duration of methotrexate's other side effects, such as nausea, dizziness, diarrhea and fatigue, according to the report in the July issue of Arthritis & Rheumatism. Rheumatoid arthritis is an autoimmune disease that most often strikes people in their 30s and 40s, especially women. The illness causes the immune system to attack tissues that line the joints, which can cause pain, inflammation and joint destruction. Methotrexate is the standard drug used to treat the condition, but about 30% of patients discontinue treatment early due to toxicity. To investigate whether folic acid and folinic acid could decrease the drug's toxic side effects, the researchers gave more than 400 patients methotrexate in addition to either 1 milligram (mg) daily of folic acid, 2.5 mg weekly of folinic acid, or an inactive placebo. Doses of methotrexate began at 7.5 mg weekly and increased to a maximum of 25 mg a week. After 48 weeks, 38% of patients taking the placebo had stopped treatment with methotrexate, compared with 17% of patients taking folic acid and 12% of patients taking folinic acid. Patients taking the placebo had higher levels of liver enzymes than patients taking folate supplements, the report indicates. High levels of liver enzymes indicate toxicity to the liver. ``Both folate supplementation regimens reduced the incidence of elevated liver enzyme levels during methotrexate therapy and, as a consequence, methotrexate was discontinued less frequently in these patients,'' conclude Dr. Annelies E. van Ede from University Medical Center St. Radboud in Nijmegen, the Netherlands, and colleagues. The researchers add that any possible negative effect of folate supplementation on the efficacy of the drug can be overcome by increasing the dosage. Indeed, by the end of the study, patients taking folate needed higher amounts of methotrexate to achieve the same impact on their arthritis as patients taking methotrexate with placebo.

SOURCE: Arthritis & Rheumatism 2001;44:1515-1524.