Smoking Linked to Lower Anti-TNF Effectiveness in IBD

Key Takeaways

• Among patients with UC or CD receiving advanced therapy, active smoking was associated with lower anti-TNF effectiveness than never smoking.
• Across advanced therapies overall, the smoking association weakened after repeated treatment courses within patients were accounted for.
• Former smokers had outcomes comparable to never smokers; active smokers required more treatment courses than never smokers in both UC and CD.
• No significant differences were shown for vedolizumab or ustekinumab, although the smaller samples were not sufficient to rule out a clinically relevant effect.

For patients with ulcerative colitis (UC) or Crohn’s disease (CD), investigators assessed whether active, former, and never smoking status tracked with different outcomes during contemporary advanced treatment. They retrospectively identified patients with IBD receiving advanced therapies from an electronic database and included those with a documented smoking history in a Medicina study. The cohort included 346 patients, including 136 with UC and 210 with CD, and 614 treatment courses across anti-tumor necrosis factor (TNF), vedolizumab, ustekinumab, Janus kinase (JAK) inhibitor, interleukin-23 (IL-23) inhibitor, and etrasimod therapy. The anti-TNF analysis included 371 infliximab or adalimumab courses after 11 golimumab courses were excluded. The primary outcome was clinical response and remission, and secondary outcomes included endoscopic improvement, the need for advanced-therapy sequencing, and surgery.

Never smokers had greater anti-TNF effectiveness than active smokers in adjusted analyses, with OR 1.44, 95% CI 1.04-2.00; p = 0.03. That association remained significant after repeated treatment courses within patients were modeled, with OR 1.35, 95% CI 1.01-1.80; p = 0.04. Across advanced therapies overall, the adjusted association also favored never smokers, OR 1.25, 95% CI 1.01-1.55; p = 0.04, but became non-significant after repeated-course modeling. Former smokers had outcomes comparable to never smokers, active smokers required more treatment courses than never smokers in both UC and CD (p = 0.03), and no significant differences were shown for vedolizumab or ustekinumab.

These findings reflect associations from a retrospective single-center cohort rather than causal effects, and the clearest signal was reported for anti-TNF therapy rather than uniformly across all advanced therapies.

The authors concluded that smoking was associated with a negative impact on anti-TNF effectiveness in both UC and CD, and the finding supports systematic smoking cessation counseling and patient education as part of IBD management.

Clinician Questions

Which advanced therapies were included in the smoking-status analysis in inflammatory bowel disease?

The analysis included anti-TNF therapy, vedolizumab, ustekinumab, Janus kinase inhibitor therapy, interleukin-23 inhibitor therapy, and etrasimod. The anti-TNF effectiveness analysis itself was limited to infliximab and adalimumab after golimumab courses were excluded.

How broadly do the smoking findings in IBD appear to apply across drug classes?

The clearest reported association was with anti-TNF therapy, while the overall advanced-therapy signal weakened after repeated treatment courses were taken into account. No significant differences were demonstrated for vedolizumab or ustekinumab.

What outcomes were measured in the smoking analysis for patients with UC or CD receiving advanced therapy?

The primary outcome was the rate of clinical response and remission. Secondary outcomes included endoscopic improvement, the need for advanced-therapy sequencing, and surgery.