Pos0480 Sufficient Methotrexate-Polyglutamate Concentrations Is Associated With Future Improvement in Joint Inflammation Detected by Ultrasonography in Patients With Rheumatoid Arthritis： Subanalysis From the Magik Study

Background: Methotrexate (MTX) is widely used as an anchor drug in the treatment of rheumatoid arthritis (RA) because of its established efficacy. However, a part of patients shows poor response regardless of MTX dose escalation or experience adverse events, which can be partly ascribed to the difference in MTX metabolism. Intracellular MTX-polyglutamates (PGs) concentrations, active form of MTX metabolites, are associated with improvement in clinically assessed disease activity. In recent years, musculoskeletal ultrasonography (MSUS) has been increasingly used to assess synovitis sensitively, however, the association of increased MTX-PG concentrations and synovitis on MSUS has not been clarified. Objectives: To investigate the relationship of MTX-PG levels with effectiveness of MTX detected with MSUS in MTX-naïve patients with RA. Methods: We prospectively enrolled 79 patients in this analysis from the MAGIK study, which was a 76-week cohort study measuring MTX-PG concentrations in patients with RA. Among them, twenty-six patients were completely assessed for 40 joints of MSUS at baseline, week 12, and week 36 after MTX initiation. Patients who started biological agents within 36-week were excluded, resulting in 14 patients included in the analyses. Erythrocyte MTX-PG levels were measured by mass spectrometry. The associations of MTX-PG concentrations with disease activity including DAS28 and grayscale (GS)/power doppler signal (PD) score of MSUS were analysed. Results: Characteristics of patients included in the analysis were following: a median age was 65 years, 85.7% were female, and a median DAS28 of 4.03 (Table 1). The mean concentrations of total MTX-PG levels were elevated with MTX dose escalation, while MTX-PG3 concentrations showed a slow, delayed increase after 12-week. The mean number of swollen joints by examination at baseline and week 36 were 3.07 and 0.88, respectively, while the mean number of GS-positive joints and PD-positive joints with MSUS were 4.79 and 3.79 at baseline and 2.17 and 1.08 at week 36, respectively. Linear regression analysis revealed no relationship between MTX-PG concentrations and the changes in DAS28, swollen/tender joint counts, and serum CRP levels. In contrast, higher MTX-PG3 and total MTX-PG concentrations at 24-week were significantly associated with greater improvement in the number of PD-positive joint detected with MSUS at 36-week (r=0.66, p=0.0133 and r=0.69, p=0.0088, respectively) and total MSUS scores of 40 and 28 joints at 36-week, especially in the total PD score (Table 2). Conclusion: In patients with RA treated with MTX monotherapy, sufficient MTX-PG3 and total MTXPG concentration can lead to future improvement in joint inflammation detected sensitively with MSUS. REFERENCES: [1] Takahashi C, et al. RMD Open. 2017;3(1):e000363. Acknowledgements: NIL. Disclosure of Interests: None declared.