Site hosted by Angelfire.com: Build your free website today!
Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis

Ortiz Z, Shea B, Suarez Almazor M, Moher D, Wells G, Tugwell P.

A substantive amendment to this systematic review was last made on 30 November 1997. Cochrane reviews are regularly checked and updated if necessary.

Data collection and analysis: Two observers extracted the data and assessed the quality of the trials. (BS, Z0) The overall treatment effect across trials was calculated using a fixed effect model. Disease activity was evaluated using standardized mean differences to ensure comparability across outcome measures. Results are presented with 95% Confidence Inervals (95% CI). Subgroup analyses were conducted evaluating different doses and sensitivity analysis looking at the quality of the trials. Publication bias was assessed with an inverted funnel plot technique. Heterogeneity of the trials was measured using a standard chi square test. Costs per month in different countries were compared.
Citation: Ortiz Z, Shea B, Suarez Almazor M, Moher D, Wells G, Tugwell P.
Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis (Cochrane Review). In: The Cochrane Library, Issue 3, 1999. Oxford: Update Software.

Background and objectives:Reviewers' 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.

Search strategy: We searched the Cochrane Musculoskeletal Group trials register and Medline up to Oct 1997, using the search strategy developed by the Cochrane Collaboration. (Dickersin 1994).

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 ( <20 mg / week) concurrently with folate supplementation.

Main results: Of the 12 trials retrieved, 7 met the inclusion criteria. The total sample included 307 patients, of which 147 were treated with folate supplementation, 80 patients with folinic acid and 67 patients with folic acid. A 79% reduction in mucosal and GI side effects was observed for folic acid [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.