GLASGOW, SCOTLAND – Patients who smoke are substantially less likely to respond to biologic treatment for rheumatoid arthritis than are those who have never smoked.
The percentage of current smokers who responded to treatment with anti–tumor necrosis factor-alpha (anti-TNF-alpha) drugs at 6 months was just 27%, compared with 90% of never smokers and 63% of ex-smokers in a retrospective study of 359 patients.
Similarly poor response to rituximab was seen in patients who were current smokers, with respective response rates for current, ex-, and never smokers of 20%, 68%, and 98%.
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Because smokers respond poorly to biologics for rheumatoid arthritis, some physicians wonder if they should be given such treatment in the first place.
A response was defined as a mean change in 28-joint disease activity score (DAS28) of 1.2 or greater, according to the U.K. National Clinical for Health and Clinical of Excellence (NICE) definition.
This begs the controversial question of whether current smokers should be given treatment with biologic agents unless they quit smoking, said Dr. Abdul Khan, a rheumatology specialist trainee at St. George’s Hospital in London, speaking at the annual meeting of the British Society for Rheumatology.
Working with Dr. David L. Scott, Dr. Khan assessed whether two simple pretreatment biomarkers – rheumatoid factor (RF) and smoking status – could help predict the response to biologic therapy for RA (Rheumatology 2012;51:iii41-2, abstract O40). They studied 209 patients treated with anti-TNFs and 150 treated with rituximab. The mean age of patients was 56 years for the anti-TNF treated patients and 61 years for the rituximab group. The mean disease duration was 8 years and 13 years, respectively, and 61% and 53% were RF positive.
Primary outcome assessments included the 6-month change in DAS28 and calculation of NICE responders (DAS28 change greater than or equal to 1.2). Smoking status was assessed as being current, previous, or never. Dr. Khan observed that a more detailed evaluation of smoking history might be warranted in future investigations, such as the calculation of pack years. RF status was determined, and anticitrullinated protein autoantibody (ACPA) positivity was determined for patients receiving rituximab therapy.
The mean change in DAS28 scores after 6 months’ anti-TNF therapy for never smokers was 2.6. For current smokers, the mean change was just 0.9 and for ex-smokers, it was 1.39. Corresponding figures for rituximab were 2.92, 0.63, and 1.49.
RF status predicted responses to rituximab but not to anti-TNFs, with a mean change of 2.14 for RF-positive patients and 0.98 for RF-negative patients treated with rituximab after 6 months.
Combining RF and ACPA status showed significant effects with regards to response to rituximab – 80% of never but only 22% of current smokers responded to treatment at 6 month if they were positive for both RF and ACPA
"Smoking and rheumatoid factor/ACPA status had an additive effect on DAS28 responses," Dr. Khan reported. Of 55 never smokers, 46 were RF/ACPA positive and nine were negative and almost all (98%) were NICE responders, with the mean fall in DAS28 score of 2.77.
Strikingly different results were seen for current smokers, however, with 50% of RF-positive patients responding, compared with 3% of RF-negative patients. Previous smokers showed intermediate response rates between those of current and never smokers.
Aside from the other well-documented health risks of smoking – including an increased risk of cardiovascular and pulmonary complications such as chronic obstructive pulmonary disease and lung cancer – these data suggest that patients with RA would do well to give up smoking if they currently smoke.
Indeed, in a press statement, Dr. Scott, professor of rheumatology at King’s College in London, suggested that "these findings show what a dramatic effect modifying your lifestyle, such as giving up smoking, can have on treatment outcomes."
Dr. Khan noted that they also raise an ethical dilemma for clinicians. "The balance of evidence suggests that biologics are unlikely to be cost effective in RA patients who continue to smoke.
"This observation creates a complex ethical dilemma which needs to be addressed."
Dr. Khan and Dr. Scott had no financial disclosures.