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

The impact of smoking on TNF inhibition (TNFi) therapy is unclear. We examined the effect of smoking on all-cause and cause-specific TNFi discontinuation in axial spondyloarthritis (axSpA). We used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS). Patients fulfilling the ASAS criteria for axSpA, who started their first TNFi, were eligible for analysis. Inverse-probability weights were used to balance differences in baseline disease severity and other confounders. We used marginal structural Cox proportional hazard models to estimate hazard ratios (HR) for TNFi discontinuation according to smoking status. In analyses of cause-specific discontinuation, competing risk events were considered as censoring, using inverse-probability weights. A total of 758 participants were included in the analysis (66% male, mean age 45 years), providing 954 patient-years of follow-up. TNFi was discontinued in 174 (23%) patients, among whom 26% stopped due to infections, 20% due to other adverse events and 44% due to inefficacy or other reasons. Thirty-four percent were current smokers and 30% ex-smokers. Compared to never smokers, current smokers' risk of TNFi discontinuation was HR 0.79 (95%CI 0.53 to 1.20) and ex-smokers HR 0.68 (95%CI 0.45 to 1.04). Our data did not show evidence that current smoking influenced discontinuation due to infections (HR 0.79, 95%CI 0.40 to 1.54), other adverse events (HR 0.86, 95%CI 0.41 to 1.78) or inefficacy/other causes (HR 1.44, 95%CI 0.86 to 2.41). Baseline smoking status did not impact TNFi discontinuation in this UK cohort of axSpA participants.