Smoking Status and Cause-Specific Discontinuation of Tumour Necrosis Factor Inhibitors in Axial Spondyloarthritis

Sizheng Steven Zhao; Kazuki Yoshida; Gareth T. Jones; David M. Hughes; Stephen J. Duffield; Sara K. Tedeschi; Houchen Lyu; Robert J. Moots; Daniel H. Solomon; Nicola J. Goodson


Arthritis Res Ther. 2019;21(177) 

In This Article


The aetiological and prognostic roles of cigarette smoking in rheumatoid arthritis are well-established, but its role in axial spondyloarthritis (axSpA) remains unclear. Clinically meaningful differences in response to TNF inhibitors (TNFi) have not been demonstrated in axSpA when continuous outcomes are used, such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).[1–3] In contrast, analyses using binary response variables, such as BASDAI50 (50% reduction), found current smokers to have significantly lower odds of TNFi response compared to never smokers.[1,4] Since all causes of discontinuation are often counted as non-response, increased drug discontinuation in smokers may explain this discrepancy.

One prior study reporting increased risk of treatment discontinuation in smokers did not adjust for socioeconomic status, comorbidities or baseline disease severity.[4] Since these are potential confounders or known predictors of TNFi discontinuation,[5] limited conclusions can be drawn about the independent relationship between smoking and TNFi discontinuation.

Patients stop TNFi for several reasons, including inefficacy, adverse events or other reasons, such as patients' social circumstances. Infections are adverse events of special interest since smoking is a substantial risk factor for bacterial and viral infections.[6] Whether the effect of smoking differs according to each cause of TNFi discontinuation is not known. Once treatment is stopped for one reason (e.g. adverse events), the individual can no longer be at risk of other causes of discontinuation (e.g. inefficacy) in that treatment episode. When an event either precludes observation of the outcome of interest or modifies its probability, "competing risks" is present.[7] When competing risks are not rare, i.e. > 5% of the population, traditional survival analyses should not be used and additional methodological considerations are needed to appropriately understand a potential association between smoking and TNFi discontinuation.

The aim of the current analyses was to examine the impact of smoking on all-cause and cause-specific TNFi discontinuation in patients with axSpA, using marginal structural models to address the above methodological issues.