Guest guest Posted June 19, 2010 Report Share Posted June 19, 2010 Institute of Pharmacology Polish Academy of Sciences Pharmacological Reports 2006 " Methotrexate in rheumatoid arthritis " Excerpt: Folate supplementation during MTX therapy Folic acid and folinic acid reduce some adverse events (gastrointestinal intolerance, stomatitis, hepatotoxicity, hyperhomocysteinaemia, alopecia) associated with MTX, so most of rheumatologists recommended all patients taking MTX to take them as well even though this may be accompanied by a slight reduction in efficacy. A very important report on folic acid supplementation was published by et al. [76]. The patients received placebo or 5 or 27.5 mg of folic acid weekly. This study demonstrated that folate intake leads to a reduction in side effects without reduced efficacy. In a 48-week trial, Hoekstra et al. analyzed the toxicity of MTX in patients who received either folic acid or placebo. The addition of folate was strongly associated with a lack of hepatotoxicity [43]. Van Ede et al. demonstrated in a randomized controlled trial that treatment with either folate regimen resulted in a reduction in the incidence of liver enzyme elevations [111]. Patients receiving folate were less likely to discontinue MTX than patients in the placebo group, but folate supplementation was associated with higher mean doses of MTX. Another reason to use folic acid in MTX-treated patients is for its effectiveness in reducing plasma homocysteine levels. Hyperhomocysteinemia is an independent risk factor for coronary artery disease, and premature mortality in patients with RA is caused by accelerated atherosclerosis. Slot demonstrated in a small study that Phomocysteine concentrations negatively correlated with erythrocyte folate after four weeks. P-homocysteine and erythrocyte folate were measured before the start of MTX treatment, after four weeks of MTX treatment, and after further four weeks of treatment with MTX supplemented with folic acid (15 mg per week). The author concluded that treatment with MTX induced a significant rise in P-homocysteine that was neutralized by folic acid supplementation [103]. After a meta-analysis, Whittle at al. proposed that folic acid supplements be prescribed routinely to all patients receiving MTX for the treatment of RA. They recommended 5 mg of oral folic acid given in the morning following the day of MTX administration. The folic acid dose can be increased if the side effects continue. Folate supplements do not appear to significantly reduce the effectiveness of MTX in the treatment of RA, so the benefits outweights the risk [119]. In patients in whom folic acid is not adequate, one can try using folinic acid (initial dose: 5 mg/week) administrated 24 h after MTX. Discussions about the necessity of folic acid supplementation were resumed after the publication of a post hoc analysis of two randomized, controlled studies by Khanna et al. Nine to 21% fewer MTX treated RA patients taking folic acid had American College of Rheumatology (ACR) 20%, 50%, or 70% improvement at 52 weeks compared with those who did not receive folic acid, so some rheumatologists believe that prophylactic prescription of folic or folinic acid to all RApatients receiving MTX is not required [26, 52]. *************************************** Read the full article here: http://www.if-pan.krakow.pl/pjp/pdf/2006/4_473.pdf Not an MD Quote Link to comment Share on other sites More sharing options...
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