Prediction of response to disease modifying antirheumatic drugs in rheumatoid arthritis.
OBJECTIVE
To investigate potential predictors of response to conventional DMARDs in RA.


METHODS
Study design - 6-month follow-up prospective study.


METHODS
RA patients with active disease. INTERVENTION AND FOLLOW-UP: Introduction of one DMARD. Response to treatment evaluated at 6 months (ACR20 criteria).


METHODS
Potential predictors of response, patients' demographics, disease activity, percentages of PBMC subsets expressing P-gp, serum IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α levels, were evaluated using univariate and multivariate logistic regression analysis. ROC curve analyses were performed in order to obtain thresholds allowing the prediction of response.


RESULTS
Forty-two patients (mean age = 57 ± 13 years, mean disease duration = 5.4 ± 7.2 years) were included. MTX was given to 30. The response to therapy was predicted by the baseline serum level of TNF-α (mean = 30.2 pg/ml ± 18 in non-responders vs. 11.9 pg/ml ± 11.2 in responders). The threshold, which predicted with the best accuracy the response to treatment, was 20.1 pg/ml (sensitivity, specificity, positive and negative predictive values of 75, 78.9, 83.3, and 69.2%, respectively; AUC = 80.3%, 95% CI = 62.8-97.7%). Similar results were obtained in the subgroups of patients treated with MTX and patients with early RA of less than 3 years duration.


CONCLUSIONS
In the present work, the serum concentration of TNF-α was related to further response to DMARDs. Other works are needed for confirmation and to assess whether such biomarker could be used to predict the response to DMARDs at the individual level.
Maillefert
Jean-Francis
JF
Inserm U887, Department of rheumatology, hôpital Général, Dijon University Hospital, University of Burgundy, 3, rue du Fb-Raines, 21078 Dijon, France. jean-francis.maillefert@chu-dijon.fr
Puéchal
Xavier
X
Falgarone
Géraldine
G
Lizard
Gérard
G
Ornetti
Paul
P
Solau
Elisabeth
E
Legré
Virginie
V
Lioté
Frédéric
F
Sibilia
Jean
J
Morel
Jacques
J
Maynadié
Marc
M
D018501:Antirheumatic Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007596:Joints / Q000473:pathology / Q000503:physiopathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D010146:Pain / Q000503:physiopathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D018501:Antirheumatic Agents; D015415:Biomarkers; D008727:Methotrexate; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014409:Tumor Necrosis Factor-alpha