Smoking and overweight determine the likelihood of developing rheumatoid arthritis

Abstract

ObjectivesRheumatoid arthritis (RA) is a prototypic chronic inflammatory disease with a debilitating course if untreated. A genetic predisposition for RA is known, and its occurrence is associated with the presence of autoantibodies in the serum and with environmental factors. It is unknown if smoking and overweight are contributory factors for developing RA in individuals with RA-specific autoantibodies in the serum.MethodsFifty-five individuals at risk for developing RA, based on the presence of RA-specific autoantibodies in the serum, who never had any evidence of arthritis upon physical examination, were followed over time. Smoking was assessed as being never or ever smoker and body mass index as <25 (normal) or ≥25 kg/m2 (overweight). Clinical endpoint was the occurrence of arthritis. Proportional hazard regression analysis was performed to investigate the potential of (combinations of) variables in predicting the onset of arthritis over time.ResultsAfter a median follow up time of 13 (IQR 6–27) months, 15 individuals (27%) developed arthritis. Smoking was associated with the development of arthritis (HR (95% CI): 9.6 (1.3 to 73.0); p=0.029). Overweight was, independently of smoking, associated with arthritis (HR (95% CI): 5.6 (1.3 to 25.0); p=0.023). The overall arthritis risk of 28% after a median of 27 months follow up increased to 60% in individuals with a smoking history combined with overweight.ConclusionsThis is the first prospective study showing that smoking and overweight increase the risk of development of arthritis in a cohort of autoantibody-positive individuals at risk for developing RA. These results show the importance of life style factors in development of RA and should be critically evaluated in future clinical research aimed at disease prevention.

A new window of opportunity in rheumatoid arthritis

“…It is therefore difficult to speculate whether their modification would be sufficient to rescue a high risk phenotype where systemic autoimmunity is well established and clinical and/or imaging features have often already developed in the joints. A smoking history and elevated BMI were associated with an increased risk of arthritis development in seropositive at risk individuals in one small study [49]. This is in keeping with data from the US Nurses Health Studies, where elevated BMI was associated with seropositive and seronegative RA development [50].…”

Smoking Behavior Changes in the Early Rheumatoid Arthritis Period and Risk of Mortality During Thirty‐Six Years of Prospective Followup

“…Smoking influences transitions between preclinical phases in the development of RA (27)(28)(29). Smoking may contribute to RA pathogenesis by interacting with the HLA-DRB1 shared epitope to increase RA risk, perhaps through the formation of citrullinated neoantigens, resulting in loss of tolerance, autoimmunity, and systemic inflammation, eventually resulting in polyarthritis (30)(31)(32)(33).…”

Pre-rheumatoid arthritis and its prevention

“…It is also found that nulliparity increases RA risk. Obesity is also an important risk factor for RA in western countries, as being overweight increases the levels of circulatory leptins and stimulates proinflammatory cytokines such as TNFα and interleukin-1 (20).…”