Journal d'immunologie clinique et cellulaire
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Effects of Smoking on Immunologic and Skeletal Mechanisms Involved in Rheumatoid Arthritis and Responses of Various Biologic Therapies for RA

Katherine L. Molnar-Kimber

Smoking is considered a major risk factor in the onset of rheumatoid arthritis. Smokers who also carry the HLA-DR4 shared epitope have a higher risk of development of RA. Smoking releases more than 4000 compounds which not only affect the cardiovascular and respiratory systems but also bone and joint health. Smokers have a higher risk for bone fractures, development of osteoporosis, and degeneration of intervertebral discs. Bone fractures of most smokers heal slower than those of most controls. Smoking also lowers bone mineral density, increases production of proinflammatory cytokines, and augments the risk of citrullination of proteins in the lungs, and possibly in the joints. RA patients who generated antibodies to cyclic citrullinated proteins (CCP) have a higher risk for joint erosions. Although response rates are significantly higher in nonsmoking early RA patients than nonsmoking RA patients with long-standing disease, response rates are not significantly improved in smoking early RA patients. Smoking has decreased response rates to TNF blockers. Additional studies indicated that smoking significantly reduced the response rate of infliximab but not etanercept or adalimumab in RA patients. Because one TNF blocker (infliximab) had significantly lower response rates in a subpopulation of RA patients (smokers versus never smokers) than two distinct TNF blockers, criteria for the development and approval of biosimilars may need to include in vivo trials as well as a demonstration of activity against the primary target (e.g. TNFα). Although the most straight forward recommendation is for patients to stop smoking, investigations on the effect of smoking on response to therapies may serve as a model for elucidating the effect of other environmental contaminants such as air pollution on the response to treatment of flares in RA patients.