Smoking is an important risk factor for developing the most common form of rheumatoid arthritis (RA) and other inflammatory diseases, but a critical question remains: Can people who quit smoking delay or prevent RA, or have they permanently and irrevocably altered their risk of the disease? New research by investigators from Brigham and Women’s Hospital examines that question using data from the Nurses’ Health studies, the first of which was started in 1976 at the Harvard School of Public Health and is now in its 42nd year. Their findings, which appear in the journal Arthritis Care & Research, demonstrate for the first time that changing behavior — in this case, sustained smoking cessation — can reduce the risk of developing seropositive RA, the more severe form of the disease.
“Ours is the first study to show that a behavior change can reduce risk for seropositive RA,” said corresponding author Jeffrey Sparks, an associate physician in the Brigham’s rheumatology division and an assistant professor of medicine at Harvard Medical School. “Risk isn’t just about genes and bad luck. There’s a modifiable environmental component to the onset of this disease and a chance for some people to reduce their risk or even prevent RA.”
To conduct their study, Sparks and his colleagues used data from the original Nurses’ Health Study and the Nurses’ Health Study II, a second cohort established in 1989. Both studies asked registered nurses from across the U.S. who filled out health surveys every two years for information about smoking and health status. Among more than 230,000 participants in this analysis, the researchers identified 1,528 who developed RA. They were especially interested in the 969 seropositive (as opposed to seronegative) patients, who have auto-antibodies related to the disease and generally have more severe symptoms, including joint deformities and disability.
For seropositive RA, risk began to lower about five years after women quit smoking and continued to decrease the longer they did not smoke. Participants who quit for good reduced their risk of seropositive RA by 37 percent after 30 years. The team did not find any association between seronegative RA and smoking, adding further evidence to the theory that seronegative and seropositive RA may be two distinct diseases with distinct risk factors.
“One of the lessons here is that it takes sustained smoking cessation to reap the full benefit,” said Sparks. “Whereas for other diseases, such as cardiovascular disease, quitting smoking can provide a more immediate effect, here we’re seeing benefits decades later for those who quit smoking permanently.”
While the biological mechanisms that link smoking and the development of RA are unclear, Sparks and others think the habit may affect a preclinical disease process that leads to the formation of RA-related auto-antibodies and increases inflammation. In addition to continuing to study the biology of RA, Sparks and his colleagues want to extend their investigations to include men and interventional trials among active smokers to see if it is possible to prevent the formation of RA-related auto-antibodies and slow or halt the progression of the disease among those at increased risk.
This work was supported by the National Institutes of Health.