The Evidence Is In: Smoking Causes Rheumatoid Arthritis

As emphatic as they are in calling to end smoking, the nation’s soldiers against tobacco are a cautious lot when it comes to making scientific calls. No finding of a report to the Surgeon General on smoking has ever been reversed, according to Terry F. Pechacek, PhD, associate director for science at the Office of Safety and Health (OSH), and a veteran at crafting multiple reports. That may be why more than 25 years passed between the first study connecting smoking and rheumatoid arthritis (RA) and the finding in the most recent Surgeon General’s Report that the “evidence is sufficient” that smoking causes RA.

The report, released January 17, 2014,¹ finds this and more.Pechacek and Tim McAfee, MD, MPH, director of OSH, sat down with Evidence-Based Immunology and Infectious Disease to discuss the findings about RA and other ailments in The Health Consequences of Smoking—50 Years of Progress, which was released to mark the anniversary of the landmark 1964 report²

that kicked off the public crusade against cigarettes.

The new report prominently adds RA to the roster of diseases definitely caused by smoking.¹ What’s more, it declares that smoking cigarettes makes modern therapies to treat the disease, the tumor necrosis factor-alpha (TNFalpha) inhibitors, less effective,¹ raising important questions for both providers and payers as they decide how to treat smokers who have RA.

RA is a debilitating, chronic autoimmune disease with a different mechanism than the better-understood osteoarthritis, which causes pain due to wear and tear on the joints.³ RA almost seems to attack from the inside out, inflaming the lining of the joints with a painful swelling that can cause a distinguishing deformity.^1,3 The connection between smoking and RA was first discovered in 1987 during a study of the disease among women taking oral contraceptives,⁴ and while there is consensus that both genetic and environmental components play a role in its development, “Exposure to tobacco smoke has demonstrated the most consistent association,”⁵ according to Jennifer Gorman, writing for Arthritis & Rheumatism in 2006. The precise connection remained unclear, although smoking was believed to have an immunosuppressive effect.⁵

Pechacek noted that the new report documents how not just RA, but the immune system generally, is adversely affected by smoking’s “7000 chemicals, including over 250 that are really dangerous.” When the chemicals in cigarette smoke harm the immune system, he said, it’s not a reach to understand how they also blunt therapies designed to give it a boost; thus, the report concludes that those who continue to smoke inhibit their own treatment, not only for RA but also for cancer, diabetes, and other diseases. “Smoking disrupts the overall body,” Pechacek said. “We expect that we will keep finding more things that it disrupts—diseases we would not have thought of 10 or 20 years ago are related to smoking because of these systemic effects.”

The report’s findings follow a 2010 metaanalysis that pooled data from 18 studies to examine the effect of smoking on persons with rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) disease,² determinants of the presence of RA. Results found that the overall risk for developing RA was 1.4 (95% confidence interval [CI], 1.25-1.58) for ever smokers, 1.35 (95% CI, 1.17-1.55) for current smokers, and 1.25 (95% CI, 1.10-1.40)6 for past smokers compared with never smokers. While studies to demonstrate that cigarette smoking increases RA severity remain controversial, evidence that continued smoking reduces the effectiveness of TNF-alpha inhibitors is strong.⁷ In fact, response rates to these new therapies tracks smoking history, with those who have never smoked getting the best results, those who still smoke seeing the worst results, and those who have quit smoking seeing results in between.¹

McAfee, who previously practiced with Group Health in Seattle, Washington, has used the occasion of the anniversary report to call on healthcare providers to stop avoiding the obvious: when treating a patient with cancer, RA, or another disease caused or aggravated by smoking, it makes no sense to treat the condition and ignore the smoking. “I would hope that over the next few

years there is going to be increased pressure, from a number of different areas in society, toward addressing tobacco use in clinical settings where it’s relevant—which it usually is. It’s pretty hard to find an area in medicine where if someone has a chronic or acute illness there isn’t a negative role being played by their smoking,” McAfee said.

The lost life expectancy alone should be discussed, he said. Historically, reward structures in medicine have not conditioned physicians or other healthcare providers to take on a patient’s smoking, but McAfee said that is changing, as it must. “We’ve got to change that mentality,” he said, because smoking is a huge contributor to mortality and morbidity. “In most cases, the intent and the desire to address smoking is there, but the system just doesn’t reward it.”