title: Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis.
abstract: OBJECTIVE
  To study the impacts of 1) the delay from the onset of symptoms to the institution of disease-modifying antirheumatic drug (DMARD) therapy, 2) two treatment strategies (treatment with a combination of DMARDs or with a single drug), and 3) the presence of HLA-DRB1 alleles (shared epitope) on the prediction of disease remission after 2 years in patients with early rheumatoid arthritis (RA).
  
  
  METHODS
  In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial, 195 patients with recent-onset RA (median duration 6 months) were randomly assigned to receive either 1) a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or 2) a single DMARD with or without prednisolone. The presence of a shared epitope was tested for in 165 of the 178 patients completing the study. The additional variables of age, sex, presence of rheumatoid factor, number of fulfilled American College of Rheumatology criteria for the classification of RA, and length of delay from onset of symptoms to institution of therapy were entered into a logistic regression model to determine the significant predictors for remission at 2 years.
  
  
  RESULTS
  The delay to therapy (cut point of 4 months) was the only significant predictor for remission in patients treated using the single-DMARD strategy, while no variable was a significant predictor for remission in those treated using the combination-DMARD strategy. The frequency of achieving remission in the combination-DMARD group after 2 years was similar in patients with short (0-4 months) and long (>4 months) delay periods (11 of 26 patients and 22 of 53 patients, respectively [approximately 42% in each group]), while the corresponding frequencies in the single-DMARD group were 8 of 23 patients (35%) and 7 of 63 patients (11%) (P = 0.021). The presence of a shared epitope was not related to the induction of remission.
  
  
  CONCLUSIONS
  The delay of a few months from the onset of symptoms to institution of therapy decreases the ability of the traditional single-drug strategy to induce remission in early RA.
authors.affiliation: Department of Medicine, Turku University Central Hospital, Turku, Finland. timo.mottonen@tyks.fi
authors.forename: Timo
authors.initials: T
authors.lastname: Möttönen
authors.forename: Pekka
authors.initials: P
authors.lastname: Hannonen
authors.forename: Markku
authors.initials: M
authors.lastname: Korpela
authors.forename: Martti
authors.initials: M
authors.lastname: Nissilä
authors.forename: Hannu
authors.initials: H
authors.lastname: Kautiainen
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Leena
authors.initials: L
authors.lastname: Laasonen
authors.forename: Oili
authors.initials: O
authors.lastname: Kaipiainen-Seppänen
authors.forename: Per
authors.initials: P
authors.lastname: Franzen
authors.forename: Tapani
authors.initials: T
authors.lastname: Helve
authors.forename: Juhani
authors.initials: J
authors.lastname: Koski
authors.forename: Marianne
authors.initials: M
authors.lastname: Gripenberg-Gahmberg
authors.forename: Riitta
authors.initials: R
authors.lastname: Myllykangas-Luosujärvi
authors.forename: Marjatta
authors.initials: M
authors.lastname: Leirisalo-Repo
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011237:Predictive Value of Tests; D011239:Prednisolone / Q000008:administration & dosage; D012074:Remission Induction; D012460:Sulfasalazine / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D011239:Prednisolone; D008727:Methotrexate