title: Treatment strategies in patients with rheumatoid arthritis for whom methotrexate monotherapy has failed: data from the NOR-DMARD register.
abstract: OBJECTIVE
  To compare the effectiveness of adding synthetic disease-modifying antirheumatic drugs (sDMARDs) versus tumour necrosis factor α inhibitors (TNFi) to methotrexate (MTX) in patients with rheumatoid arthritis (RA) who were MTX inadequate responders (IR). Second, to examine outcomes in patients receiving MTX+TNFi for whom the MTX+sDMARD combination had also failed.
  
  
  METHODS
  Patients with RA (disease duration ≤ 5 years, MTX IR and naïve to other DMARDs) starting treatment with MTX+TNFi or MTX+sDMARDs were included. From the latter group a subgroup of patients who went on to receive MTX+TNFi was identified.
  
  
  RESULTS
  Patients receiving MTX+TNFi (n=98) and MTX+sDMARDs (n=129) had similar baseline disease activity when starting combination therapy (mean Disease Activity Score 28 (DAS28) = 4.90 and 4.96, respectively). Three- and 6-month effectiveness and 2-year drug survival were better for MTX+TNFi than for MTX+sDMARDs: mean DAS28 was -1.61 versus -0.85 after 3 months (p<0.001) and -1.91 versus -1.03 after 6 months (p=0.01); DAS28<2.6 was reached by 29.0% versus 11.6% after 3 and 34.5% versus 12.9% after 6 months. Effectiveness was somewhat better with triple therapy than other MTX+sDMARD combinations but was generally inferior compared with MTX+TNFi. For the patients who received MTX+TNFi as a third step after MTX+sDMARDs had failed (n=38) there was a tendency towards lower remission rates, worse disease activity states and inferior drug survival compared with patients who received MTX+TNFi directly after the failure of MTX.
  
  
  CONCLUSIONS
  Effectiveness was better for MTX+TNFi than for MTX+sDMARDs. Patients who started MTX+TNFi after two synthetic DMARD regimens had failed had a tendency to less favourable disease states after 3 months than patients who switched directly from MTX to MTX+TNFi.
authors.affiliation: Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. elisabeth_lie@yahoo.no
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lie
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
authors.forename: Till
authors.initials: T
authors.lastname: Uhlig
authors.forename: Knut
authors.initials: K
authors.lastname: Mikkelsen
authors.forename: Synøve
authors.initials: S
authors.lastname: Kalstad
authors.forename: Cecilie
authors.initials: C
authors.lastname: Kaufmann
authors.forename: Erik
authors.initials: E
authors.lastname: Rødevand
authors.forename: Tore K
authors.initials: TK
authors.lastname: Kvien
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D055118:Medication Adherence; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D017211:Treatment Failure; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate