Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis.

Abstract:

OBJECTIVES: To assess the effects of folic acid and folinic acid in reducing the mucosal and gastrointestinal (GI) and haematologic side effects of low-dose of Methotrexate (MTX) in patients with Rheumatoid Arthritis (RA) and to determine whether or not folate supplementation alters MTX efficacy.

SEARCH STRATEGY: We searched the Cochrane Controlled Clinical Trial's Register (CCTR), the Cochrane Musculoskeletal Group Specialized Register and Medline up to and including June 1999, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). We also handsearched the following: (i) bibliographic references; (ii) current contents of the last 6 months; (iii) abstracts of the rheumatology meetings; and (iv) all issues of four journals; Journal of Rheumatology, Arthritis & Rheumatism, Clinical and Experimental Rheumatology, and British Journal of Rheumatology. All languages were included. Principal investigators were also contacted in order to look for unpublished literature.

SELECTION CRITERIA: We selected all double-blind, randomized, placebo-controlled, clinical trials (RCTs), in which adult RA patients were treated with a low dose of MTX ((OR = 0.21 (95% CI 0.10 to 0.44)).

For folinic acid, a clinically but non-statistically significant reduction of 43% was found [OR = 0. 57 (95% CI 0.28 to 1.15)]. No major differences were observed between low and high doses of folic or folinic acid. Haematologic side effects could not be analyzed, since details of each haematologic side effect by patients were not provided. No consistent differences in disease activity parameters were observed when comparing placebo and folic or folinic acid at low or high doses, although patients on high dose folinic acid had an increase in the number of tender joints, but not swollen joints. Large differences in costs across countries were found, but folinic acid was more expensive in all.

REVIEWER'S CONCLUSIONS: The results support the protective effect of folate supplementation in reducing MTX side effects related to the oral and GI systems. We could not determine if folic was different from folinic acid. Therefore, for folinic acid to be considered cost-effective it must be found more effective than folic acid at reducing MTX side effects.