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


Among a total of 2420 participants in the BSRBR-AS, 840 commenced their first TNFi within the study period and had smoking status recorded at baseline. Eighty-two participants were excluded because they did not have a valid baseline assessment. Excluded participants had longer symptom duration, more frequently met classification criteria for AS and were more frequently male (full comparison in Additional file 1: Table S1). Seven hundred fifty-eight participants were included in the analysis set, providing 954 patient-years of follow-up. The median follow-up time was 1.0 year (inter-quartile range 0.4 to 2.0 years).

TNFi was discontinued in 174 (23%) patients. The median time to discontinuation was 6 months (inter-quartile range 3 to 11). Among those who stopped TNFi, 26% stopped due to infections, 20% due to other adverse events and 44% due to inefficacy or other reasons, with no differences according to smoking status. Recoding of discontinuation causes is shown in Additional file 1: Table S2.

Baseline characteristics of the analysis cohort are shown in Table 1. Thirty-four percent of patients were current smokers, 30% ex-smokers and 36% never smokers. Current smokers were younger, were more frequently male and showed trends for having higher deprivation and lower educational attainment. Current smokers also more frequently had elevated CRP. The three groups did not differ in age of symptom onset. Current smokers reported worse baseline disease activity and functional impairment. Covariate imbalance was negligible (standardised mean differences < 0.1) after weighting for IPTW (Additional file 1: Figure S1).

All-cause TNFi Discontinuation

Using marginal structural models, hazard ratios for all-cause TNFi discontinuation did not significantly differ in current (HR 0.79; 95%CI 0.53 to 1.20) or ex-smokers (HR 0.68; 95%CI 0.45 to 1.04), compared to never smokers. Unadjusted Kaplan-Meier estimators are shown in Additional file 1: Figure S2.

Cause-specific TNFi Discontinuation

Hazard ratios for each of the three causes of TNFi discontinuation according to smoking status are shown in Table 2. Our data did not provide evidence that current or previous smoking affected discontinuation due to infection, other adverse events or inefficacy/other reasons.