Major Findings

A review of six clinical trials found that concurrent use of folic acid or folinic acid in patients with rheumatoid arthritis receiving methotrexate (MTX) resulted in a reduction in mucosal, gastrointestinal, hepatic, and hematologic side effects, as well as a decrease in the rate of MTX discontinuation.

Reasons for Side Effects

MTX suppresses the immune system by inhibiting the growth of normal cells, which helps to improve rheumatoid arthritis symptoms. However, it can affect rapidly dividing cells, such as those found in the gastrointestinal tract, liver, and blood cells, potentially causing side effects. Folic acid or folinic acid are vitamins necessary for cell growth, and they can help mitigate these side effects caused by MTX.

Common Side Effects

Gastrointestinal Side Effects

Gastrointestinal side effects from MTX were reduced by 26% (9% absolute risk reduction) with the concurrent use of folic acid or folinic acid. These side effects include nausea, vomiting, and abdominal pain.

Hepatic Dysfunction

Hepatic dysfunction caused by MTX was reduced by 76.9% (16% absolute risk reduction) with the concurrent use of folic acid or folinic acid. Hepatic dysfunction is measured by elevated serum transaminase levels.

Hematologic Side Effects

While there was some evidence suggesting that folic acid or folinic acid could reduce hematologic side effects from MTX, the data quality was low and did not allow for a firm conclusion.

Strategies for Managing Side Effects

Managing Gastrointestinal Side Effects

Concurrent use of folic acid or folinic acid is recommended to mitigate gastrointestinal side effects from MTX.

Managing Hepatic Dysfunction

Concurrent use of folic acid or folinic acid is recommended to mitigate hepatic dysfunction from MTX.

Managing Hematologic Side Effects

Concurrent use of folic acid or folinic acid is recommended to mitigate hematologic side effects from MTX, but the low data quality does not allow for a firm conclusion.

Comparison Across Studies

Similarities in Studies

All studies were double-blind, placebo-controlled, randomized trials that involved patients with rheumatoid arthritis receiving MTX treatment.

Differences in Studies

There were variations across studies in the type of folic acid or folinic acid used, the dosage, the method of administration, and the duration of the study.

Practical Implications and Cautions

Patients with rheumatoid arthritis who are receiving MTX treatment may benefit from the concurrent use of folic acid or folinic acid to reduce side effects. However, the use of these supplements should be under the guidance of a healthcare professional. Avoid self-medication and consult with your doctor before taking folic acid or folinic acid.

Limitations of Current Research

All studies in this review involved patients with rheumatoid arthritis receiving MTX treatment. Further research is required to assess the effects of MTX treatment in other diseases and therapeutic settings.

Future Research Directions

Further research is needed to determine whether concurrent use of folic acid or folinic acid influences the therapeutic effectiveness of MTX in patients with rheumatoid arthritis. Additionally, further investigation is necessary to determine the optimal dosage and administration methods for folic acid or folinic acid.

Conclusion

The findings of this review suggest that concurrent use of folic acid or folinic acid in patients with rheumatoid arthritis receiving MTX treatment may lead to a reduction in mucosal, gastrointestinal, hepatic, and hematologic side effects, as well as a decrease in the rate of MTX discontinuation. However, further research is warranted.