Methotrexate and folic acid supplementation in rheumatoid arthritis: A Japanese claims database and 538,985 patients from April 2015 to November 2020.

OBJECTIVES

To assess the use of laboratory monitoring, folic acid supplementation, and folinate calcium therapy in patients with rheumatoid arthritis (RA) receiving first-line methotrexate (MTX) according to the 2019 Japan College of Rheumatology safety updates and using a large Japanese claims database (DeSC).

MATERIALS AND

METHODS

Patient data for the period 2015 - 2020 were retrieved from the database, and patients were identified who had presented with active disease. The number of patients commencing with MTX treatment and receiving concomitant disease-modifying antirheumatic drug and folic acid supplementation were determined together with information on recommended laboratory testing (blood tests, serum creatinine, chest radiography, and KL-6) in the year prior to MTX initiation. The impact of the 2019 Japan College of Rheumatology guidelines was assessed by comparing the extent of folic acid supplementation before and after publication of the guidelines.

RESULTS

Of the 1,574 patients identified with active RA, 919 (58.4%) started MTX. Folic acid was co-administered in 85.1% of MTX users, with no significant change in supplementation rates before and after the introduction of the 2019 guidelines (81.8 vs. 82.2%, p = 0.56), indicating that these safety protocols were already well-established. Baseline blood tests were carried out in 99.8% and chest radiography in 69.2% of patients. After commencing MTX treatment, the monitoring of serum creatinine (87.2 vs. 93.7%, p < 0.05) and KL-6 (15.2 vs. 28.4%, p < 0.05) increased significantly. The frequency of chest radiography decreased to 56.0% (p < 0.05), reflecting a shift toward more sensitive diagnostic tools in clinical practice. No patients required folinate calcium rescue therapy.

CONCLUSION

MTX prescribing and monitoring in RA is generally carried out in accordance with clinical guidelines. Although folic acid supplementation is recommended and widely implemented, ~ 20% of patients do not receive it. Monitoring is generally carried out rigorously, but safety data indicate that these measures should receive more attention in high-risk elderly populations who were probably under-represented in this study.