Similarly, it is unlikely that association between psychological distress and anti-TNF discontinuation could be explained by the presence of CVD since the association between HADS-T and CVD was not significant (data not shown), while both were significant in the multivariate analyses. It is possible that conditions linked to psychological distress (such as fibromyalgia) may have an influence on these findings, but patients were not assessed for fibromyalgia in our study.Īlthough CVD showed an association with ever having smoked (p = 0.03), it did not explain the association between py (> 30) and anti-TNF discontinuation, since both were highly significant in the multivariate analyses. Discontinuation of anti-TNF treatment is clearly a complex, multidimensional endpoint that may be influenced by biological, emotional, and sociological factors 15. Despite this relationship, psychological distress and py (> 30) were independently associated with discontinuation of anti-TNF therapy, as were a raised DAS28 and evidence of CVD at baseline. Psychologically distressed patients (particularly depressed ones) were more than twice as likely to be current smokers at the start of anti-TNF therapy.
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Of 166 patients recruited, 4 were excluded from the analysis because of incomplete or missing questionnaires. All patients were followed up at 3 months, 12 months, and 12-monthly intervals thereafter. The major reasons for discontinuation were adverse events or inefficacy (as defined by British Society for Rheumatology guidelines) 14. Py were stratified into 4 categories (i.e., 0, 1-15, 16-30, > 30) to reflect smoking intensity.ĭiscontinuation of therapy was investigated only in patients who were previously anti-TNF- or other biologic-naive, and was not assessed in those starting a second anti-TNF agent. Smoking history was obtained from a patient-completed questionnaire and quantified in pack-years (py) 1 py was equivalent to 20 cigarettes per day for 1 year. Combining the scores of the 2 scales was used to obtain a “total score” as a measure of general psychological distress 13. Probable anxiety and depression at baseline was defined using the Hospital Anxiety and Depression Scale (HADS) 11, cutoff score of ≥ 8 12. History of cardiovascular or cerebrovascular disease (CVD) included angina, ischemic heart disease, myocardial infarction, heart failure, or cerebrovascular accident, but excluded hypertension. Evidence of comorbid conditions were obtained from the medical notes and review of patient medication. Ethical approval was obtained from the North Staffordshire local research ethics committee, and all patients provided written informed consent.ĭemographic and clinical variables were recorded at baseline and regular intervals thereafter. All patients starting therapy with TNF antagonists since 2002 (n = 166) were recruited. Patients attended a hospital clinic at the Staffordshire Rheumatology Centre, UK, and satisfied the 1987 American College of Rheumatology criteria for RA 10. We investigated the relationship between smoking and psychological distress, and whether these and other factors are independently associated with discontinuation of anti-TNF therapy.
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Studies on the association of depression 6 and smoking 8 with response to TNF antagonists did not address their influence on discontinuation of treatment.
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Cigarette smoking is also associated with a worse anti-TNF response 7, 8, 9, but the relationship with psychological stress has not been explored. Recently we demonstrated that in patients with RA treated with tumor necrosis factor-α (anti-TNF), those with persistent depression had a lower reduction in the 28-joint count Disease Activity Score (DAS28) at 3 months than those without depression 6. Discontinuation of therapy with TNF antagonists is independently associated with psychological distress, heavy smoking, and CVD at baseline.Īnxiety and depression occur commonly in patients with rheumatoid arthritis (RA) and can influence perception of well-being and severity of symptoms 1, 2, 3, 4, 5.