Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis.
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.
Möttönen
Timo
T
Department of Medicine, Turku University Central Hospital, Turku, Finland. timo.mottonen@tyks.fi
Hannonen
Pekka
P
Korpela
Markku
M
Nissilä
Martti
M
Kautiainen
Hannu
H
Ilonen
Jorma
J
Laasonen
Leena
L
Kaipiainen-Seppänen
Oili
O
Franzen
Per
P
Helve
Tapani
T
Koski
Juhani
J
Gripenberg-Gahmberg
Marianne
M
Myllykangas-Luosujärvi
Riitta
R
Leirisalo-Repo
Marjatta
M
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
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D011239:Prednisolone; D008727:Methotrexate