Impact of Smoking on the Effectiveness of Advanced Therapies in Inflammatory Bowel Disease: Active Smoking Is Associated with Reduced Effectiveness of Anti-TNF Treatment

Background and Objectives: Smoking is a well-established risk factor for Crohn’s disease (CD), whereas patients with ulcerative colitis (UC) who smoke may exhibit a milder disease course. The impact of smoking on the efficacy of advanced therapies (AT) in patients with inflammatory bowel disease (IBD) remains largely unknown. Materials and Methods: Patients with IBD receiving AT and with a detailed smoking history were retrospectively identified from our electronic database. The primary outcome was the rate of clinical response and remission. Secondary outcomes included endoscopic improvement, the need for AT sequencing, and surgery. Results: A total of 346 patients (136 UC and 210 CD) were analyzed, with a mean age of 47.3 years and a mean disease duration of 14.1 years (range, 0.5–48 years). Overall, 614 treatment courses were evaluated: 382 anti-TNF, 92 vedolizumab, 84 ustekinumab, 36 JAK inhibitor, 16 IL-23 inhibitor, and 4 etrasimod treatment courses. The anti-TNF effectiveness analysis included 371 infliximab/adalimumab courses after exclusion of 11 golimumab courses. A total of 107 patients (30.9%) were active smokers and 76 (21.9%) were former smokers. Anti-TNF therapy was significantly more effective in never smokers than in active smokers in the adjusted analysis (OR 1.44, 95% CI 1.04–2.00; p = 0.03), and this association remained significant in the mixed-effects model accounting for repeated treatment courses within patients (OR 1.35, 95% CI 1.01–1.80; p = 0.04). The association for advanced therapies overall was significant in the adjusted model (OR 1.25, 95% CI 1.01–1.55; p = 0.04) but was attenuated after accounting for repeated courses (OR 1.10, 95% CI 0.99–1.22; p = 0.07). No statistically significant differences were demonstrated for vedolizumab or ustekinumab, although the smaller sample sizes preclude exclusion of a clinically relevant effect. Former smokers had outcomes comparable to never smokers. Active smokers also required significantly more treatment courses than never smokers in both UC and CD (p = 0.03). Conclusions: Smoking is associated with a negative impact on the effectiveness of anti-TNF therapy in both UC and CD, highlighting the need for systematic smoking cessation counseling and patient education as an integral component of IBD management.