Serum cotinine as a biomarker of tobacco exposure and the association with treatment response in early rheumatoid arthritis.
OBJECTIVE
Cigarette smoking has emerged as a risk factor for the development of rheumatoid arthritis (RA). Recent studies have suggested that cigarette smoking may lead to lower treatment response rates with methotrexate (MTX) and some biologic agents in RA. Knowledge of whether tobacco exposure reduces treatment efficacy is important, since smoking could represent a modifiable factor in optimizing RA treatment.


METHODS
The study participants included patients with early RA (<3 years in duration) enrolled in the Treatment of Early Aggressive Rheumatoid Arthritis study, a randomized, blinded, placebo-controlled clinical trial comparing early intensive therapy (MTX + etanercept or MTX + hydroxychloroquine + sulfasalazine triple therapy) versus initial treatment with MTX with step-up to MTX + etanercept or to triple therapy if the disease was still active at 24 weeks. Serum cotinine was measured using a commercially available enzyme-linked immunosorbent assay at baseline and at 48 weeks, with detectable concentrations at both visits serving as an indicator of smoking status. The mean Disease Activity Score in 28 joints (DAS28) was compared by smoking status, adjusting for baseline disease activity.


RESULTS
Of the 412 subjects included in the analysis, 293 (71%) were categorized as nonsmokers and 119 (29%) as current smokers. There were no differences in the mean DAS28 score between 48 and 102 weeks based on smoking status for the overall group (P = 0.881) or by specific treatment assignment.


CONCLUSIONS
Among patients enrolled in a large randomized controlled trial of early RA with poor prognostic factors, smoking status did not impact treatment responses for those receiving early combination or initial MTX with step-up therapy at 24 weeks if the disease was still active.
University of Nebraska Medical Center, Omaha, NE 68198-3025, USA.
Leann B
LB
Maska
Harlan R
HR
Sayles
James R
JR
O'Dell
Jeffrey R
JR
Curtis
S Louis
SL
Bridges
Larry W
LW
Moreland
Stacey S
SS
Cofield
Ted R
TR
Mikuls
D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D003367:Cotinine / Q000097:blood*; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000008:administration & dosage; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects* / Q000097:blood; D012460:Sulfasalazine / Q000008:administration & dosage; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D015415:Biomarkers; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D003367:Cotinine; D000068800:Etanercept; D008727:Methotrexate