People who have rheumatoid arthritis and who smoke cigarettes, or who have a history of smoking, are more likely to fail treatment on powerful biologic drugs than people who don’t smoke, according to a new study published in the May 15, 2009, issue of the Journal of Rheumatology.

Researchers at the University Hospital of North Staffordshire in the United Kingdom studied 154 people with rheumatoid arthritis who started treatment with medications that block an inflammatory protein called tumor necrosis factor alpha, or TNF-alpha, in 2002.

TNF-alpha blocking drugs include etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), golimumab (Simponi), and certolizumab pegol (Cimzia).

The researchers then calculated study participants' smoking habits based on average pack years. One pack year equals 20 cigarettes smoked every day for one year.

Scientists found that smoking is associated with a poor response to TNF-alpha blockers in people who have rheumatoid arthritis, and the more intense the smoking habit, the higher the failure rate – whether they were smoking when they started the TNF-alpha therapy or not.

Derek Mattey, the lead researcher, is a senior scientist at the Staffordshire Rheumatology Centre at the University Hospital of North Staffordshire. He says there are several possible reasons that smokers have a poor response and further research is needed to determine that for sure. But he says researchers do know that smoking is associated with an autoantibody positive type of rheumatoid arthritis, which is more likely to be severe, and may therefore show a poorer response to treatment. In this study though, he says the relationship between poor response and a history of smoking was independent of the presence of rheumatoid factor.

“This suggests that reasons other than production of rheumatoid factor are responsible for the relationship,” Dr. Mattey says. “We do not know if smoking interferes directly with the medication, but the fact that we see an effect in people who have given up smoking, often many years before, suggests that smoking may have long-lasting effects on the physiology of these patients, which influences their response.“

This begs the question of whether longtime smokers who are having a poor response to TNF drugs will see a difference if they suddenly give up their habit. “It appears that the damage may already have been done,” Dr. Mattey says. “Patients who had given up smoking before taking anti-TNF showed a worse response than patients who had never smoked. The amount that a patient has previously smoked seems to be more important than whether or not they are smoking at the time of starting anti-TNF therapy.”

Mark C. Fisher, MD, is a research scientist with the Division of Rheumatology at New York University’s School of Medicine in New York City. He has studied the potential impact of smoking cessation on rheumatoid arthritis disease activity and says this is an impressive study that adds to the argument that smoking and rheumatoid arthritis are a bad combination.

“I think it delves into why do some patients get better and not others, because with all the medicines that have come out in the last few years, there are still some patients that don’t get better,” Dr. Fisher says. “It tells you the larger your smoking burden the worse off you are, but it doesn’t necessarily definitively answer the question of if you stop smoking are you unlikely to have any benefit or will you still have some benefit.”

Still, Dr. Mattey and Dr. Fisher agree that the consensus in the medical community is that people with rheumatoid arthritis who smoke should stop.