Relationship Between Pack-year History of Smoking and Response to Tumor Necrosis Factor Antagonists in Patients with Rheumatoid Arthritis

Objective: To determine whether there is a quantitative relationship between smoking history and response to therapy with tumor necrosis factor (TNF) antagonists.

Methods: A history of cigarette smoking was obtained from a questionnaire completed by each patient starting therapy with TNF antagonists since 2002 (n=154). A core set of demographic and clinical variables was recorded at baseline and at 3 and 12 months. The extent of smoking was quantified in pack-years (py), with 1 py equivalent to 20 cigarettes per day for 1 year. The association between smoking intensity and response was assessed using contingency tables and logistic regression analysis. Response to therapy was defined according to the European League Against Rheumatism improvement criteria.

Results: There was an increasing trend of no response at 3 and 12 months with increasing py history [p (trend)=0.008 and 0.003, respectively]. The change in Disease Activity Score (DAS)28 over the first 3 months was inversely associated with the number of py (r=-0.28, p=0.002). The association of py history with response failure was independent of age, sex, disease duration, baseline disease activity score (DAS28), Health Assessment Questionnaire (HAQ) score, IgM rheumatoid factor, and smoking at baseline. The most significant effect was seen in patients treated with infliximab.

Conclusion: RA patients with a history of smoking were more likely to show a poor response to TNF antagonists. Response failure was associated with the intensity of previous smoking, irrespective of smoking status at initiation of anti-TNF therapy.