title: Reduction in Serum Uric Acid May Be Related to Methotrexate Efficacy in Early Rheumatoid Arthritis: Data from the Canadian Early Arthritis Cohort (CATCH).
abstract: OBJECTIVE
  The mechanism of action of methotrexate in rheumatoid arthritis (RA) is complex. It may increase adenosine levels by blocking its conversion to uric acid (UA). This study was done to determine if methotrexate lowers UA in early RA (ERA).
  
  
  METHODS
  Data were obtained from Canadian Early Arthritis Cohort, an incident ERA cohort. All ERA patients with serial UA measurements were included, comparing those with methotrexate use vs. no methotrexate exposure (controls). Analyses were exploratory. Patients with concomitant gout or taking UA-lowering therapies were excluded.
  
  
  RESULTS
  In total, 49 of the 2,524 ERA patients were identified with data available for both pre-methotrexate UA levels and post-methotrexate UA levels (300 µmol/L and 273 µmol/L, respectively; P = 0.035). The control group not taking methotrexate had a mean baseline UA level of 280 µmol/L and a follow-up level of 282 µmol/L (P = 0.448); mean change in UA with methotrexate was -26.8 µmol/L vs. 2.3 µmol/L in the no methotrexate group (P = 0.042). Methotrexate users with a decrease in UA had a disease activity score of 2.37 for 28 joints when compared with the controls (3.26) at 18 months (P = 0.042). Methotrexate users with decreased UA had a lower swollen joint count (SJC) of 0.9 at 18 months, whereas methotrexate users without lowering of UA had an SJC of 4.5 (P = 0.035). Other analyses were not significant.
  
  
  CONCLUSIONS
  Methotrexate response is associated with lowering of serum UA in ERA compared to nonusers. This may be due to changes in adenosine levels. Methotrexate response is associated with lower UA and fewer swollen joints compared to nonresponders.
authors.affiliation: Rheumatology, Western University, London, ON, Canada.; Clinical Pharmacology, Western University, London, ON, Canada.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Rheumatology, Hospital for Special Surgery, New York City, NY, USA.
authors.forename: Vivian P
authors.initials: VP
authors.lastname: Bykerk
authors.affiliation: Clinical Pharmacology, Western University, London, ON, Canada.
authors.forename: George K
authors.initials: GK
authors.lastname: Dresser
authors.affiliation: Rheumatology, Universite de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: Boire
authors.affiliation: Rheumatology, Institut de Rhumatologie, Montreal, QC, Canada.
authors.forename: Boulos
authors.initials: B
authors.lastname: Haraoui
authors.affiliation: Rheumatology, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Carol
authors.initials: C
authors.lastname: Hitchon
authors.affiliation: Rheumatology, Southlake Regional Health Centre, Newmarket, ON, Canada.
authors.forename: Carter
authors.initials: C
authors.lastname: Thorne
authors.affiliation: Rheumatology, Southlake Regional Health Centre, Newmarket, ON, Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Tin
authors.affiliation: Rheumatology, Vancouver Coastal Health, Vancouver, BC, Canada.
authors.forename: Shahin
authors.initials: S
authors.lastname: Jamal
authors.affiliation: Rheumatology, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Keystone
authors.affiliation: Rheumatology, Western University, London, ON, Canada.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Pope
keywords: Nested case-control; early rheumatoid arthritis; methotrexate; uric acid