CORRELATION BETWEEN METHOTREXATE PLASMA CONCENTRATION AND CLINICAL EFFICACY IN RHEUMATOID ARTHRITIS: A 6-MONTH PROSPECTIVE STUDY

Background: Methotrexate (MTX) is the first-line disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA), with therapeutic efficacy often attributed to optimal systemic exposure. However, interindividual variability in MTX plasma concentration can influence treatment response. Objective: To evaluate the correlation between plasma MTX concentrations and clinical efficacy over a 6-month period in patients with RA, using ESR, CRP, and pain scores as markers of therapeutic response. Methods: A prospective observational study was conducted on 72 newly diagnosed RA patients receiving oral MTX (15 mg/week). Plasma samples were collected at 2 hours post-dose to estimate MTX concentration using validated HPLC. Disease activity was assessed at baseline and after 6 months using ESR, CRP, and visual analogue scale (VAS) pain scores. Pearson’s correlation was used to assess associations between MTX levels and clinical parameters. Results: The mean MTX plasma concentration at 6 months was 1.29 ± 0.39 µmol/L. Reductions in mean ESR (from 34.4 to 19.9 mm/hr), CRP (from 13.2 to 6.0 mg/L), and pain score (from 6.53 to 1.98) were noted. However, weak and statistically non-significant correlations were found between MTX concentration and ESR (r = +0.16, p = 0.17), CRP (r = -0.21, p = 0.07), and pain score (r = -0.08, p = 0.47). Conclusion: While MTX therapy led to significant clinical improvement in RA patients over 6 months, plasma concentration alone did not strongly predict therapeutic response. Intracellular MTX metabolites and other pharmacodynamic factors may play a more dominant role, indicating the need for more comprehensive monitoring strategies.