Smoking May Choke Off Benefits of TNF Inhibitors


Registry data show that smokers with spondyloarthropathies have markedly less improvement in disease activity on TNF inhibitors. The evidence also suggests that quitting the smoking habit erases this disadvantage.

Ciurea A, Scherer A, Weber U, et al., Impaired response to treatment with tumour necrosis factor α inhibitors in smokers with axial spondyloarthritis.Ann Rheum Dis. 2015; Feb 9.  doi: 10.1136/annrheumdis-2013-205133. [Epub ahead of print]

Kydd ASR, Chen JS, Makovey J et al., Smoking did not modify the effects of antiTNF treatment on health related quality of life among Australian ankylosing spondylitis patients. Rheumatology. 2015; 54: 310317. doi: 10.1093/rheumatology/keu314. First  published online: August 29, 2014

Axial spondylitis (axSpA) patients who smoke may be robbing themselves of the benefits of tumor necrosis alpha (TNF-α) blocking drugs, especially if they have elevated levels of C-reactive protein, say Swiss researchers.

Their study of almost 700 axSpA patients shows that, compared with non-smokers, current smokers have smaller improvements in both the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) a year after starting their first TNF inhibitor.

The odds for reaching a 50% improvement in BASDAI response or the ASAS criteria for 40% improvement after a year were significantly lower in current smokers than in non-smokers.

Around 40% had elevated CRP at baseline, and CRP levels normalized for fewer of the smokers.

“Smoking ... may also increase pain levels by influencing neurological processing of sensory information or by unspecific tissue damage due to hypoxia or vasoconstriction,” the authors comment.

However, quitting may benefit patients since past smoking didn’t seem to lower TNF treatment effectiveness, at least in this study.

What isn’t clear is whether smoking affects response to individual TNF drugs approved for axSpA. (Around two-thirds of patients received either adalimumab [Humira] or etanercept [Enbrel].)

The data from 698 patients in the ongoing Swiss Clinical Quality Management Cohort for axSpA (SCQMaxSpA)  reflect real-life patients in clinical practice, the authors say.

In contrast, smoking doesn’t seem to alter the effects of TNF drugs on health related quality of life (HR-QoL) in ankylosing spondylitis (AS), according to a similar longitudinal study from Australia, even though current smokers report lower physical function.

The 8-year study involved 422 AS patients on TNF-α drugs in the Australian Rheumatology Association Database. Similar to the Swiss study, the subjects were largely men in their 40s. Half were non-smokers.

After adjusting for smoking, gender, age, co-morbidities, and medication use all HRQoL measures improved significantly 2 years after starting a TNF inhibitor. Levels of improvement were similar for current smokers and non-smokers.

While smokers did have lower physical function scoreson the short- form 36 (SF-36) and on the health assessment questionnaire for spondylitis (HAQ-S), the differences are not clinically significant.

Both studies are limited by the observational nature of the data.

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