Impact of tobacco smoking on response to tumour necrosis factor-alpha inhibitor treatment in patients with ankylosing spondylitis: results from the Danish nationwide DANBIO registry

Rheumatology (Oxford). 2016 Apr;55(4):659-68. doi: 10.1093/rheumatology/kev392. Epub 2015 Nov 30.


Objectives: To investigate the association between tobacco smoking and disease activity, treatment adherence and treatment responses in patients with AS treated with their first tumour necrosis factor-alpha inhibitor (TNFi) therapy in routine care.

Methods: Observational cohort study based on the Danish nationwide DANBIO registry. Kaplan-Meier plots, Cox and logistic regression analyses by smoking status (current/never/previous) were calculated for treatment adherence and BASDAI 50%/20 mm-response. Additional stratified analyses were performed for gender and TNFi-type.

Results: Of 1576 AS patients included in the study, 1425(90%) had known smoking status (current/never/previous: 43%/41%/16%). The median follow-up time was 2.02 years (IQR 0.69-5.01). At baseline, current smokers compared with never smokers had longer disease duration (4 years (1-12)/2 years (0-10)), higher BASDAI (61 mm (47-73)/58 mm (44-70)), BASFI (53 mm (35-69)/46 mm (31-66)) and BASMI (40 mm (20-60)/30 mm (10-50)) scores (all P < 0.01). Current and previous smokers had shorter treatment adherence than never smokers (current: 2.30 years (1.81-2.79) (median (95% CI)); previous: 2.48 years (1.56-3.40), never: 4.12 years (3.29-4.95)), P < 0.0001). Similar results were found in multivariate analyses (current versus never smokers, HR 1.41 (95% CI 1.21-1.65), P < 0.001), most pronounced among men. Current smokers had poorer 6 months' BASDAI50%/20 mm-response rate than never smokers (42%/58%, P < 0.001). In multivariate analyses, current smokers had lower odds of achieving BASDAI50%/20 mm-response than never smokers, both overall (OR 0.48 (95% CI 0.35-0.65), P < 0.0001) and for the different TNFi-types (adalimumab 0.45 (0.27-0.76)/etanercept 0.24 (0.10-0.61)/infliximab 0.57 (0.34-0.95)).

Conclusion: In this study of TNFi-treated AS patients in clinical practice, current and previous smokers had significantly poorer patient-reported outcomes at baseline, shorter treatment adherence and poorer treatment response compared with never smokers.

Keywords: Ankylosing spondylitis; Outcome; Routine care; Smoking; Tumour necrosis factor-alpha inhibitors.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Antirheumatic Agents / therapeutic use*
  • Denmark / epidemiology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Medication Adherence / statistics & numerical data
  • Middle Aged
  • Registries
  • Smoking / adverse effects
  • Smoking / epidemiology*
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / epidemiology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antirheumatic Agents
  • TNF protein, human
  • Tumor Necrosis Factor-alpha