Smoking and Obesity Lower Treatment Success with TNF Inhibitors in Axial Spondyloarthritis

A multinational study published in BMC Rheumatology, involving nearly 15,000 patients with axial spondyloarthritis (axSpA) has found that smoking and elevated body mass index (BMI) substantially reduce the effectiveness of tumor necrosis factor inhibitor (TNFi) therapy. The findings, derived from 14 European rheumatology registries, underscore the critical need to address lifestyle factors when initiating biologic treatment.

The study included 14,885 biologic-naïve adults with axSpA who started their first TNFi therapy and had lifestyle data—such as smoking status, alcohol use, and BMI—recorded within 30 days of treatment initiation. Treatment response at 3 and 12 months was evaluated using standardized outcome metrics, including BASDAI-50, ASDAS, and ASAS response criteria.

Key findings from the 12-month data include:

• Smokers were 23% less likely to achieve a BASDAI-50 response than non-smokers (adjusted odds ratio [aOR]: 0.77; 95% CI: 0.68–0.86).
• Overweight and obese individuals showed even poorer outcomes, with aORs of 0.76 (95% CI: 0.66–0.87) and 0.53 (95% CI: 0.45–0.63), respectively.
• Interestingly, current alcohol users had a 47% higher chance of response (aOR: 1.47; 95% CI: 1.16–1.87), though this finding was not supported by sensitivity analyses and is likely non-causal.

These associations were consistent across multiple treatment response measures and remained robust after adjusting for age, sex, country, disease duration, and baseline disease activity.

“Smoking and high BMI decrease the odds of bDMARD treatment success in axSpA. Rheumatologists should consider referral to smoking cessation and/or weight management interventions at the time of commencing therapy, to enhance treatment response,” the authors concluded. “The relationship between alcohol and treatment response is unlikely to be causal and warrants further investigation.”

Reference
Jones GT, Rotariu O, MacDonald R, Michelsen B, et al. The relationship between lifestyle factors and outcome of treatment with TNFα inhibitors in axial spondyloarthritis - results from 14 European countries. BMC Rheumatol. 2025 Jul 11;9(1):88. doi: 10.1186/s41927-025-00529-4. PMID: 40646655; PMCID: PMC12247191.