title: Effects of changing from oral to subcutaneous methotrexate on red blood cell methotrexate polyglutamate concentrations and disease activity in patients with rheumatoid arthritis.
abstract: 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 MTXGlu(n)) concentrations, disease activity, and adverse effects.
  
  
  METHODS
  Thirty patients were changed from oral to SC MTX. Trough RBC MTXGlu(n) 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
  MTXGlu(3), MTXGlu(4), and MTXGlu(5) concentrations, but not MTXGlu(1) and MTXGlu(2), 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 MTXGlu(5) (p = 0.035) and RBC MTXGlu(3-5) (p = 0.032). No change in adverse effect frequency occurred.
  
  
  CONCLUSIONS
  Changing to SC MTX results in increased long-chain MTXGlu(n). However, it takes at least 6 months for RBC steady-state concentrations to be achieved. Increased long-chain MTXGlu(n) concentrations were significantly associated with reduced disease activity.
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand. lisa.stamp@cdhb.govt.nz
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Stamp
authors.forename: Murray L
authors.initials: ML
authors.lastname: Barclay
authors.forename: John L
authors.initials: JL
authors.lastname: O'Donnell
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Jill
authors.initials: J
authors.lastname: Drake
authors.forename: Christopher
authors.initials: C
authors.lastname: Frampton
authors.forename: Peter T
authors.initials: PT
authors.lastname: Chapman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D004912:Erythrocytes / Q000737:chemistry*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008727:Methotrexate / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D018501:Antirheumatic Agents; D011099:Polyglutamic Acid; C014085:methotrexate polyglutamate; D008727:Methotrexate