Smokers with Chronic Inflammatory Diseases May Respond Less to Biologics

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Smokers with chronic inflammatory diseases, especially rheumatoid arthritis (RA), may have lower odds of responding to biological therapy than non-smokers, a new study revealed.¹

“…We observed apparently lower response rates to biologic therapy after 14–16 weeks among smokers than non-smokers, but this difference was not consistent across various models,” wrote investigators, led by Maja Graves Rosenkilde Larsen, from the department of internal medicine at Molecular Diagnostics and Clinical Research Unit, University Hospital of Southern Denmark.

Chronic inflammatory diseases are highly prevalent in high-income countries. The prevalence of chronic inflammatory diseases is projected to rise due to the growing population and the aging demographics. Many chronic inflammatory diseases—ulcerative colitis, RA, axial spondylarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis—share pathological pathways and use similar treatment strategies.

Biologic disease-modifying drugs, such as TNF inhibitors, manage chronic inflammatory diseases. However, approximately 40% of patients receive no clinical response to treatment with biological agents.

Research has shown smoking tobacco, a significant risk factor for developing chronic inflammatory diseases, negatively impacts treatment responses. Despite several studies reaching this conclusion, some studies have been inconclusive. For instance, 1 study found smoking status does not affect the response to biologic therapy in patients with moderate and severe psoriasis.²

Investigators sought to compare the clinical treatment responses in patients with chronic inflammatory diseases between smokers and non-smokers.¹ They conducted a secondary analysis of the prospective BELIEVE cohort study, an observational, multicenter trial of 233 patients with a diagnosis of Crohn’s disease, ulcerative colitis, RA, AxSpA, PsA, or psoriasis initiating biologic therapy and compared treatment response rates after 14 to 16 weeks. The team evaluated the comparison between the smoker and non-smoker group using logistic regression models, a “crude” model adjusted for the chronic inflammatory disease type, and another model adjusted for sex and age.

The sample included 205 patients with 26% smokers (n = 52) and 57% ever-smokers (current, occasional, former). Smokers (43%) had a lower treatment response rate than the non-smokers (61%) (“crude” model: odds ratio [OR], 0.51; 95% CI, 0.26 – 1.01; adjusted model for sex and age: aOR, 0.51; 95% CI, 0.26 – 1.02).

The treatment response difference was more prominent among the 38 RA patients. Patients with RA who were smokers had a significantly lower treatment response than non-smokers (aOR, 0.13; 95% CI, 0.02 – 0.81).

“…Among the subgroup of RA patients, smoking was significantly associated with non-response to biologic therapy after 14–16 weeks in the ‘crude’ and adjusted model but not in the [psoriasis]-adjusted model, the latter possibly due to residual confounding,” investigators wrote.

The team wrote how the study was limited by participant enrollment ending prematurely due to the COVID-19 pandemic, and thus their sample size was not large enough to ensure power. With the small sample, they could not group smokers into “current,” “former,” and “never.”

Additionally, investigators stated how the effect of smoking cannot be investigated in a randomized controlled trial due to ethical reasons. Yet, observational studies always have the challenge of confounding.

“Despite these findings, the ‘2021 EULAR recommendations regarding lifestyle behaviors and work participation to prevent the progression of rheumatic and musculoskeletal diseases’ tentatively suggests that smoking ‘may’ influence treatment response to biologic treatment,” investigators wrote. “This uncertainty reflects that the causal relationship between smoking and treatment response cannot truly be evaluated in observational studies.”

References

1. ^{Larsen MGR, Overgaard SH, Petersen SR, et al. Effects of smoking on clinical treatment outcomes amongst patients with chronic inflammatory diseases initiating biologics: secondary analyses of the prospective BELIEVE cohort study. Scand J Immunol. Published online July 7, 2024. doi:10.1111/sji.13395}
2. ^{Constantin MM, Bucur S, Mutu CC, et al. The Impact of Smoking on Psoriasis Patients with Biological Therapies in a Bucharest Hospital. J Pers Med. 2021;11(8):752. Published 2021 Jul 30. doi:10.3390/jpm11080752}