Article type
Year
Abstract
Introduction: MTX is an antimetabolite used in the treatment of RA and is considered to be the second-line drug of first choice. MTX's side effects occur in about 60% of patients. Some side effects mimic complicated folate deficiency. Several studies have been conducted to determine if folate supplementation has a beneficial effect reducing MTX side-effects, without altering its efficacy, but the answer remains uncertain.
Objective: To determine the efficacy of FA and FNA to reduce gastrointestinal and haematologic side effects of low-dose MTX in patients with RA, and whether or not folate supplementation alters MTX efficacy.
Methods: Using the Cochrane Musculoskeletal Group search strategy, we selected all double-blind, placebo-controlled randomised clinical trials in patients who fulfilled the American Rheumatism Association's criteria for RA, older than 18 years, treated with low dose MTX (less than 20 mg/week) concurrently with folate supplementation. The outcomes were the reduction of GI and/or haematologic side effects, and the efficacy of MTX in patients who received folate supplementation. Treatment effect was calculated using a fixed effect model (Peto). Sensitivity analysis was done to compare the results with different doses and different quality of trials.
Results: Six RCTs fulfilled the inclusion criteria. Haematologic side effects could not be analysed. A significant reduction in the odds of GI side effects of 68% was shown. Considering trials that use a dose of FA or FNA less than 10mg/week, there was a significant reduction in GI side effects of 75%.
Discussion: Folate supplementation has a protective effect, reducing MTX related GI side effects, without affecting MTX efficacy. No evidence has shown that FA or FNA is the most effective.
Objective: To determine the efficacy of FA and FNA to reduce gastrointestinal and haematologic side effects of low-dose MTX in patients with RA, and whether or not folate supplementation alters MTX efficacy.
Methods: Using the Cochrane Musculoskeletal Group search strategy, we selected all double-blind, placebo-controlled randomised clinical trials in patients who fulfilled the American Rheumatism Association's criteria for RA, older than 18 years, treated with low dose MTX (less than 20 mg/week) concurrently with folate supplementation. The outcomes were the reduction of GI and/or haematologic side effects, and the efficacy of MTX in patients who received folate supplementation. Treatment effect was calculated using a fixed effect model (Peto). Sensitivity analysis was done to compare the results with different doses and different quality of trials.
Results: Six RCTs fulfilled the inclusion criteria. Haematologic side effects could not be analysed. A significant reduction in the odds of GI side effects of 68% was shown. Considering trials that use a dose of FA or FNA less than 10mg/week, there was a significant reduction in GI side effects of 75%.
Discussion: Folate supplementation has a protective effect, reducing MTX related GI side effects, without affecting MTX efficacy. No evidence has shown that FA or FNA is the most effective.