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Objective To determine the effects of changing from oral to subcutaneous (SC) methotrexate (MTX) in patients with rheumatoid arthritis (RA) on red blood cell MTX polyglutamate (RBC MTXGlun) concentrations, disease activity, and adverse effects.
Methods Thirty patients were changed from oral to SC MTX. Trough RBC MTXGlun concentrations were measured for 24 weeks and concentrations fitted to a first-order accumulation model. Disease activity was assessed by 28-joint Disease Activity Score (DAS28).
Results MTXGlu3, MTXGlu4, and MTXGlu5 concentrations, but not MTXGlu1 and MTXGlu2, increased significantly over 24 weeks, reaching 90% of new steady-state concentrations by about 40 weeks. A decrease in DAS28 was associated with increased RBC MTXGlu5 (p = 0.035) and RBC MTXGlu3-5 (p = 0.032). No change in adverse effect frequency occurred.
Conclusion Changing to SC MTX results in increased long-chain MTXGlun. However, it takes at least 6 months for RBC steady-state concentrations to be achieved. Increased long-chain MTXGlun concentrations were significantly associated with reduced disease activity.