INFO - Folic acid and folinic acid (leucovorin) for reducing side effects in patients receiving MTX for RA

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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

This is a Cochrane review abstract and plain language summary,

prepared and maintained by The Cochrane Collaboration, currently

published in The Cochrane Database of Systematic Reviews 2008 Issue 1,

Copyright © 2008 The Cochrane Collaboration. Published by Wiley

and Sons, Ltd.. The full text of the review is available in The

Cochrane Library (ISSN 1464-780X).

This version first published online: January 26. 1998

Date of last subtantive update: July 14. 1999

Abstract

Background

Methotrexate (MTX) is classified pharmacologically as an

antimetabolite due to its antagonistic effect on folic acid

metabolism. Although its mechanism of action is uncertain, it has

become the second line drug of choice for many rheumatologists

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contacted in order to look for unpublished literature.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 (<20 mg / week) concurrently with folate supplementation.

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 Intervals

(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.

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.

Authors' 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.

http://www.cochrane.org/reviews/en/ab000951.html

--

Not an MD

[Guest guest]

Thanks for this info. Very interesting..... Barbara

[ ] INFO - Folic acid and folinic acid (leucovorin) for

reducing side effects in patients receiving MTX for RA

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

This is a Cochrane review abstract and plain language summary,

prepared and maintained by The Cochrane Collaboration, currently

published in The Cochrane Database of Systematic Reviews 2008 Issue 1,

Copyright © 2008 The Cochrane Collaboration. Published by Wiley

and Sons, Ltd.. The full text of the review is available in The

Cochrane Library (ISSN 1464-780X).

This version first published online: January 26. 1998

Date of last subtantive update: July 14. 1999

Abstract

Background

Methotrexate (MTX) is classified pharmacologically as an

antimetabolite due to its antagonistic effect on folic acid

metabolism. Although its mechanism of action is uncertain, it has

become the second line drug of choice for many rheumatologists

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

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 Intervals

(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.

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.

Authors' 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.

http://www.cochrane .org/reviews/ en/ab000951. html

--

Not an MD

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