title: Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large population-based study.
abstract: BACKGROUND
  Use of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) may prevent joint damage and potentially reduce joint replacement surgeries. We assessed the association between RA drug use and joint replacement in Quebec, Canada.
  
  
  METHODS
  A cohort of new-onset RA patients was identified from Quebec's physician billing and hospitalization databases from 2002-2011. The outcome was defined using procedure codes submitted by orthopedic surgeons. Medication use was obtained from pharmacy databases. We used alternative Cox regression models with time-dependent variables measuring the cumulative effects of past use during different time windows (one model focussing on the first year after cohort entry) for methotrexate (MTX), and other DMARDs. Models were adjusted for baseline sociodemographics, co-morbidity and prior health service use, time-dependent cumulative use of other drugs (anti-tumor necrosis factor [anti-TNF] agents, other biologics, cyclooxygenase-2 inhibitors [COXIBs], nonselective nonsteroidal antiinflammatory drugs [NSAIDs], and systemic steroids), and markers of disease severity.
  
  
  RESULTS
  During follow-up, 608 joint replacements occurred among 11,333 patients (median follow-up: 4.6 years). The best-fitting model relied on the cumulative early use (within the first year after cohort entry) of MTX and of other DMARDs, with an interaction between MTX and other DMARDs. In this model, greater exposure within the first year, to either MTX (adjusted hazard ratio, HR = 0.95 per 1 month, 95% confidence interval, 95% CI 0.93-0.97) or other DMARDs (HR = 0.97, 95% CI 0.95-0.99) was associated with longer time to joint replacement.
  
  
  CONCLUSIONS
  Our results suggest that longer exposure to either methotrexate (MTX) or other DMARDs within the first year after RA diagnosis is associated with longer time to joint replacement surgery.
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. cristiano.soaresdemoura@mail.mcgill.ca.|Division of Clinical Epidemiology, McGill University Health Centre, 687 Pine Avenue West, V-Building (V2.09), Montreal, QC, H3A 1A1, Canada. cristiano.soaresdemoura@mail.mcgill.ca.
authors.forename: Cristiano S
authors.initials: CS
authors.lastname: Moura
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. michal.abrahamowicz@clinepi.mcgill.ca.|Division of Clinical Epidemiology, McGill University Health Centre, 687 Pine Avenue West, V-Building (V2.09), Montreal, QC, H3A 1A1, Canada. michal.abrahamowicz@clinepi.mcgill.ca.
authors.forename: Michal
authors.initials: M
authors.lastname: Abrahamowicz
authors.affiliation: Division of Clinical Epidemiology, McGill University Health Centre, 687 Pine Avenue West, V-Building (V2.09), Montreal, QC, H3A 1A1, Canada. marie-eve.beauchamp@clinepi.mcgill.ca.
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Beauchamp
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, BC, Canada. dlacaille@arthritisresearch.ca.
authors.forename: Diane
authors.initials: D
authors.lastname: Lacaille
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. yishu.wang@mail.mcgill.ca.
authors.forename: Yishu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada. gilles.boire@usherbrooke.ca.
authors.forename: Gilles
authors.initials: G
authors.lastname: Boire
authors.affiliation: Division of Rheumatology, Department of Medicine, Université Laval, Quebec City, QC, Canada. paul.fortin@crchudequebec.ulaval.ca.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Fortin
authors.affiliation: Division of Rheumatology, Department of Medicine, Université Laval, Quebec City, QC, Canada. louis.bessette@crchudequebec.ulaval.ca.
authors.forename: Louis
authors.initials: L
authors.lastname: Bessette
authors.affiliation: Division of Rheumatology, University of Toronto, Toronto, ON, Canada. claire.bombardier@utoronto.ca.
authors.forename: Claire
authors.initials: C
authors.lastname: Bombardier
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, ON, Canada. jessica.widdifield@utoronto.ca.
authors.forename: Jessica
authors.initials: J
authors.lastname: Widdifield
authors.affiliation: Division of Rheumatology, Department of Medicine, Dalhousie University, Halifax, NS, Canada. john.hanly@cdha.nshealth.ca.
authors.forename: John G
authors.initials: JG
authors.lastname: Hanly
authors.affiliation: École de Réadaptation, Université de Montréal, Montreal, QC, Canada. debbie.feldman@umontreal.ca.
authors.forename: Debbie
authors.initials: D
authors.lastname: Feldman
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, AB, Canada. walter.maksymowych@ualberta.ca.
authors.forename: Walter
authors.initials: W
authors.lastname: Maksymowych
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada. cpeschken@hsc.mb.ca.
authors.forename: Christine
authors.initials: C
authors.lastname: Peschken
authors.affiliation: Department of Medicine, University of Calgary, Calgary, AB, Canada. ccbarnab@ucalgary.ca.|Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada. ccbarnab@ucalgary.ca.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Barnabe
authors.affiliation: Department of Medicine, University of Calgary, Calgary, AB, Canada. sedworth@ucalgary.ca.|Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada. sedworth@ucalgary.ca.
authors.forename: Steve
authors.initials: S
authors.lastname: Edworthy
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. sasha.bernatsky@mcgill.ca.|Division of Clinical Epidemiology, McGill University Health Centre, 687 Pine Avenue West, V-Building (V2.09), Montreal, QC, H3A 1A1, Canada. sasha.bernatsky@mcgill.ca.
authors.forename: Sasha
authors.initials: S
authors.lastname: Bernatsky
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D019643:Arthroplasty, Replacement; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D011159:Population Surveillance; D011792:Quebec / Q000453:epidemiology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate