Scand J Immunol. 2024 Sep;100(3):e13395. doi: 10.1111/sji.13395.Epub 2024 Jul 7.

Maja Graves Rosenkilde Larsen ^1 2 3 4, Silja Hvid Overgaard ^1 2 4, Sofie Ronja Petersen ⁵, Karen Mai Møllegaard ^1 4, Heidi Lausten Munk ^6 7, Anders Bathum Nexøe ^8 9 10, Henning Glerup ¹¹, Tanja Guldmann ¹¹, Natalia Pedersen ¹², Sanaz Saboori ¹², Jens Frederik Dahlerup ¹³, Christian Lodberg Hvas ¹⁴, Karina Winther Andersen ^1 14, Mohamad Jawhara ¹⁴, Ole Haagen Nielsen ¹⁵, Fredrik Olof Bergenheim ¹⁵, Jacob Broder Brodersen ^1 16, Anette Bygum ^17 18, Torkell Ellingsen ⁶, Jens Kjeldsen ^10 19, Robin Christensen ^2 6, Vibeke Andersen ^1 4 8

Author information

¹Department of Internal Medicine, Molecular Diagnostics and Clinical Research Unit, University Hospital of Southern Denmark, Aabenraa, Denmark.

²Section for Biostatistics and Evidence-Based Research, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark.

³The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.

⁴Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.

⁵Department of Clinical Research, University Hospital of Southern Denmark, Odense, Denmark.

⁶Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.

⁷Center for Rheumatology and Spine Diseases, Copenhagen, Denmark.

⁸Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark.

⁹Department of Cancer and Inflammation Research, Odense University Hospital, Odense, Denmark.

¹⁰Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark.

¹¹University Research Clinic for Innovative Patient Pathways, Silkeborg Regional Hospital, Silkeborg, Denmark.

¹²Department of Gastroenterology, Slagelse Hospital, Slagelse, Denmark.

¹³Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

¹⁴Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.

¹⁵Department of Gastroenterology, Esbjerg and Grindsted Hospital, University of Southern Denmark, Esbjerg, Denmark.

¹⁶Department of Surgery, University Hospital of Southern Denmark, Aabenraa, Denmark.

¹⁷Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.

¹⁸Clinical Institute, University of Southern Denmark, Odense, Denmark.

¹⁹Research Unit of Medical Gastroenterology, Department of Clinical Research

Abstract

The prevalence and disease burden of chronic inflammatory diseases (CIDs) are predicted to rise. Patients are commonly treated with biological agents, but the individual treatment responses vary, warranting further research into optimizing treatment strategies. This study aimed to compare the clinical treatment responses in patients with CIDs initiating biologic therapy based on smoking status, a notorious risk factor in CIDs. In this multicentre cohort study including 233 patients with a diagnosis of Crohn's disease, ulcerative colitis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis or psoriasis initiating biologic therapy, we compared treatment response rates after 14 to 16 weeks and secondary outcomes between smokers and non-smokers. We evaluated the contrast between groups using logistic regression models: (i) a "crude" model, only adjusted for the CID type, and (ii) an adjusted model (including sex and age). Among the 205 patients eligible for this study, 53 (26%) were smokers. The treatment response rate among smokers (n = 23 [43%]) was lower compared to the non-smoking CID population (n = 92 [61%]), corresponding to a "crude" OR of 0.51 (95% CI: [0.26;1.01]) while adjusting for sex and age resulted in consistent findings: 0.51 [0.26;1.02]. The contrast was apparently most prominent among the 38 RA patients, with significantly lower treatment response rates for smokers in both the "crude" and adjusted models (adjusted OR 0.13, [0.02;0.81]). Despite a significant risk of residual confounding, patients with CIDs (rheumatoid arthritis in particular) should be informed that smoking probably lowers the odds of responding sufficiently to biological therapy. Registration: Clinical.Trials.gov NCT03173144.