Serum cotinine as a biomarker of tobacco exposure is not associated with treatment response in early rheumatoid arthritis.

University of Nebraska Medical Center at Omaha.
Arthritis care & research 12/2012; 64(12). DOI: 10.1002/acr.21758
Source: PubMed


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.

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.

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.

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.

10 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: It is not known whether snuff (moist smokeless tobacco) affects disease activity in rheumatoid arthritis (RA). OBJECTIVE: This study aims to study the effect of snuff on disease activity and function in Swedish patients with early RA. METHODS: Between 1992 and 2005, 2800 adult patients were included in the Better Anti-Rheumatic FarmacOTherapy (BARFOT) early RA study in Sweden. Disease Activity Score 28 joints (DAS28), Health Assessment Questionnaire, visual analog scale for general health, and drug treatment were registered at inclusion and at follow-up after 1, 2, and 5 years. European League Against Rheumatism response and remission criteria were applied at 1 year. In 2010, a self-completed postal questionnaire was sent to 2102 patients in the BARFOT study enquiring about lifestyle factors such as smoking and use of snuff. Three controls for each patient using snuff were identified. RESULTS: Fifty-one patients who used snuff were identified, together with 145 controls. When we adjusted for socioeconomic class, disease duration, and previous antirheumatic medication, the snuff users had lower DAS28 values at up to 6 months of follow-up than patients who had never smoked, and they had lower DAS28 values than previous smokers at up to 2 years of follow-up. No effect of snuff use on European League Against Rheumatism response was seen at up to 1 year. CONCLUSIONS: Snuff users initially had lower DAS28 levels than never smokers and previous smokers.
    Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 01/2013; 19(1):14-18. DOI:10.1097/RHU.0b013e31828214ed · 1.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cigarette smoking has deleterious effects on the musculo-skeletal system. The loss of bone mineral content and increased incidence of fractures are the best known negative consequences. The pathogenesis is complex, due to direct toxic effects on osteoblasts/osteoclasts activity of nicotine, and indirect actions on sex and adrenocortical hormones, vitamin D, intestinal calcium absorption, vessels and oxygen supply. Smoking may favour the onset or aggravate the progression of rheumatoid arthritis and back pain. Negative influences have been observed on muscle and on tendons. Moreover, smoking habit is associated to a number of short term post-operative complications and higher resource consumption. Smoking cessation is highly advisable with positive effects on the bone metabolism on the long term. More positive and immediate results can be obtained in patients submitted to orthopedic surgery: the healing process is improved, the frequency of complications is reduced, and the length of hospital stay is shortened.
    Muscles 04/2013; 3(2):63-9. DOI:10.11138/mltj/2013.3.2.063
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Rapidly predicting future outcomes based on short-term clinical response would be helpful to optimize rheumatoid arthritis (RA) management in early disease. Our aim was to derive and validate a clinical prediction rule to predict low disease activity (LDA) at 1 year among patients participating in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial escalating RA therapy by adding either etanercept or sulfasalazine + hydroxychloroquine [triple therapy (TT)] after 6 months of methotrexate (MTX) therapy. Methods: Eligible subjects included in the derivation cohort (used for model building, n = 186) were participants with moderate or higher disease activity [Disease Activity Score 28-erythrocyte sedimentation rate (DAS-ESR) > 3.2] despite 24 weeks of MTX monotherapy who added either etanercept or sulfasalazine + hydroxychloroquine. Clinical characteristics measured within the next 12 weeks were used to predict LDA 1 year later using multivariable logistic regression. Validation was performed in the cohort of TEAR patients randomized to initially receive either MTX + etanercept or TT. Results: The derivation cohort yielded 3 prediction models of varying complexity that included age, DAS28 at various timepoints, body mass index, and ESR (area under the receiver-operator characteristic curve up to 0.83). Accuracy of the prediction models ranged between 80% and 95% in both derivation and validation cohorts, depending on the complexity of the model and the cutpoints chosen for response and nonresponse. About 80% of patients could be predicted to be responders or nonresponders at Week 12. Conclusion: Clinical data collected early after starting or escalating disease-modifying antirheumatic drug/biologic treatment could accurately predict LDA at 1 year in patients with early RA. For patients predicted to be nonresponders, treatment could be changed at 12 weeks to optimize outcomes.
    The Journal of Rheumatology 04/2013; 40(5). DOI:10.3899/jrheum.120715 · 3.19 Impact Factor
Show more