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Current smoking was linked with an increased likelihood of a severe phenotype of Crohn's disease after adjustment for the use of biologic therapy, Canadian researchers reported.

In a multivariate analysis, the use of biologic therapy was associated with an elevated risk of severe disease phenotype, with an odds ratio of 2.137 (95% CI 1.471-3.106), but after adjustment for biologic use, the risk for smokers for severe disease was almost twofold higher (OR 1.930, 95% CI 1.112-3.350) compared with nonsmokers or former smokers, according to Neeraj Narula, MD, of the University of Ottawa, and colleagues.

Environmental factors such as cigarette smoking are known to influence Crohn's disease onset and progression. "Active smoking is associated with more aggressive disease, which includes recurrence after surgery and a poor response to medical therapy," Narula explained during a poster presentation at the

Crohn's disease has heterogeneous disease phenotypes, and there has been a lack of uniformity in defining smoking status in previous studies, such as by evaluating smoking status at the time of disease diagnosis only. The result has been uncertainty about the relationship between smoking status and severity of disease phenotype, such as stricturing or penetrating disease.

To address the question of whether smoking is associated with more advanced disease, Narula's group conducted a retrospective study of Crohn's disease patients seen at McMaster University Medical Center in Hamilton, Ontario, from 2012 to 2020.

Patients were classified as current smokers or ex- or never-smokers. Narula noted that the multivariate logistic analysis was developed with "prior knowledge and forward selection," and the analysis was adjusted for variables including current use of a biologic therapy, sex, disease duration and location, age at diagnosis, and presence of extraintestinal manifestations.

A total of 625 patients were included in the study. A stricturing phenotype was observed in 186 and a penetrating phenotype in 126. The remaining 313 patients had an inflammatory phenotype.

Smoking status was known for 492 patients: 67 were active smokers (13.6%), 85 were ex-smokers (17.3%), and 340 were never-smokers (69.1%).

In a univariate regression analysis, the odds ratio for having a stricturing or penetrating phenotype was 1.80 (95% CI 1.06-3.04) for smokers compared with ex- or never-smokers.

The researchers also conducted subanalyses of patients with the two specific advanced phenotypes. For the penetrating phenotype, smoking was associated with a doubled risk (OR 2.01, 95% CI 1.14-3.56), as was current biologic use (OR 2.06, 95% CI 1.33-3.18).

For the stricturing phenotype, smoking did not have a statistically significant association with smoking, with an odds ratio of 1.52 (95% CI 0.88-2.62), but significant associations were seen for male sex (OR 1.62, 95% CI 1.09-2.39) and current use of a biologic therapy (OR 1.61, 95% CI 1.09-2.38).

"Patients with Crohn's disease should continue to be advised on the importance of smoking cessation," the researchers concluded.

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