Correlation between serum methotrexate-polyglutamate 3 (MTX-PG3) level and disease activity in rheumatoid arthritis patients: A prospective cohort study

Background: Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, characterized by systemic inflammation, joint destruction and disability. Methotrexate (MTX) is used as the primary treatment for RA patients. However, the response to MTX therapy is highly varied and difficult to predict. This study sought to determine the role of MTX by measuring the MTX polyglutamate 3 (MTX-PG3) levels and the disease activity score 28 based on C-reactive protein (DAS28-CRP) of RA patients. Method: A prospective cohort study was conducted at the Rheumatology Polyclinic of Dr. Cipto Mangunkusumo General Hospital. Thirty-four patients with RA were included and followed up to 12 weeks. The RA patients were treated with MTX 10 mg per week and an increased dose of 5 mg per week every month. DAS28-CRP and MTX-PG3 level were assessed at week 8 and 12. Multivariate logistic regression analysis was used to determine the correlation between MTX-PG3 and DAS28-CRP. Result: A total of 34 RA patients were followed and the MTX was well tolerated in which no increase of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and glomerular filtration rate (GFR) were observed. The mean scores of DAS28-CRP decreased following the MTX-treatment: 3.93, 3.22 and 2.82 at week 0, 8 and 12, respectively. In contrast, the median concentration of MTX-PG3 increased from week 8 to week 12 followed by increasing the dose of MTX. Our analysis suggested there was a moderate positive correlation between MTX-PG3 levels and DAS28-CRP score at week 8 and week 12 post-MTX treatment. Conclusion: The level of MTX-PG3 is correlated with DAS28-CRP score suggesting that MTX-PG3 could be used as an indicator to assess the disease activity in RA patients. Nevertheless, a prospective study with a higher number of patients is needed to confirm this finding.