Background Many rheumatologists would now consider methotrexate (MTX) as the disease modifying anti-rheumatic drug (DMARD) of choice in the treatment of rheumatoid arthritis (RA). Despite having the best efficacy-toxicity profile of the DMARDs, up to 30% of patients will discontinue treatment within the first year because of adverse effects.
The mechanism of toxicity remains unclear but folate metabolism is thought to play a part. Studies have shown that folic acid (FA) is superior to folinic acid in that high (>10 mg/wk) or low dose FA reduces gastroenterological toxicity by 80%1 without loss of efficacy, and is cheaper than folinic acid. Haemotological toxicity is also more common in patients who have not received any folate supplementaion.
Various authors have suggested different FA regimes2,3 but there remains a lack of consensus on whether FA should be prescribed universally to patients taking methotrexate, whether it should be initiated only if side effects occur and what is the most effective regime?
Objectives To observe the variation in FA prescription amongst rheumatologists in Wales.
Methods A survey was conducted amongst all rheumatologists in Wales at consultant, specialist registrar, staff grade and clinical assistant levels, based at 11 district general hospitals and 1 University hospital. We asked if FA was prescribed routinely in all patients starting MTX; if so, what was the dose and frequency? If FA was prescribed daily, did it include the day of MTX administration?
Results Of the 35 rheumatologists contacted, there were 25 responses. 19 out of 25 prescribed FA routinely (76%) when initiating MTX. 3 (12%) did not prescribe FA routinely and 3 (12%) sometimes prescribed FA.
14 out of 19 (74%) who prescribed FA routinely used a dose of 5 mg/wk given 2–3 days after MTX. 2 (11%) prescribed 5 mg/day, excluding the day of MTX; 1 (5%) prescribed 10 mg/wk; 1 (5%) prescribed 5 mg twice/wk; 1 (5%) did not specify a dose. Of the 3 rheumatologists who sometimes prescribed FA,1 used a dose of 5 mg/wk; 1 prescribed 5 mg/day, excluding day of and day after MTX; 1 prescribed 1 mg/day, excluding day of MTX.
Conclusion Amongst 25 rheumatologists in Wales there are at least 6 variations in FA prescribing patterns, the most common regime being 5 mg/wk given 2–3 days after MTX. As there are no published guidelines, it would be reasonable to assume that the variation reflects the individual’s personal preference and also reflects the lack of consensus.
We are now completing a further study comparing which of these regimes appears to be most effective in reducing adverse effects of MTX amongst RA patients newly started on therapy. The results of this study are expected in July 2001.
Oritz Z, Shea B, Suarez-Alamazor ME, Moher D, Wells GA, Tugwell P. The efficacy of folic acid and folinic acid in reducing methotrexate gastroenterological toxicity in rheumatoid arthritis. A metanalysis of randomised controlled trials. J Rheumatol. 1998;25(1):36–43
Coleiro B, Mallia C. Toxicity profile of methotrexate in rheumatoid arthritis. A preliminary survey. Adv Exp Med Biol. 1999;455:359–65
Gutierrez-Urena S, Molina JF, Garcia CO, Cuellar ML, Espinoza LR. Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis. Arthritis Rheum. 1996;39(2):272–76
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