The Association Between Phenotypic Age and Primary Loss of Response to Biologic Agent in Patients with Crohn’s Disease

Xin Chen,1 Jingjing Liu,2,3 Yiping Zhang,2 Yu Wang,2 Xiao Chen,2 Qiufeng Zhao1 1Department of Radiology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 2Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 3Funan County People’s Hospital, Funan Hospital Affiliated to Fuyang Normal University School of Medicine, Fuyang, 236399, People’s Republic of ChinaCorrespondence: Xiao Chen, Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China, Email [email protected] Qiufeng Zhao, Department of Radiology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China, Email [email protected]: Loss of response (LOR) to biological agents is challenging in Crohn’s disease (CD) therapy. Identifying and predicting factors associated with therapeutic responses enables proactive intervention in high-risk LOR populations, such as adjusting therapeutic intensity or initiating second-line agents earlier, to avoid ineffective treatment and improve clinical outcomes. A few studies have also shown that biological age may be associated with treatment responses. This study aimed to show the association between phenotypic age, a type of biological age, and the primary loss of response to biological agents in patients with CD.Methods: This retrospective study included 94 CD patients, with 81 followed-up at the eighth week and 76 at the twelfth week in our institution. LOR was defined as biochemical remission (fecal calprotectin level < 250 μg/g or a reduction of > 50% from baseline levels). The phenotypic age was calculated based on a series of clinical biomarkers. Multivariate regression analysis was used to determine the association between phenotypic age and the LOR. The receiver operating characteristic curve (ROC) was used to show the performance of biological age in predicting the 8-week and 12-week LOR.Results: 33 patients had LOR at 8 weeks and 34 patients had LOR at 12 weeks. Patients with LOR had a higher phenotypic age and age gap than those with response (p < 0.001). Multivariable regression analyses further showed that phenotypic age and age gap were associated with LOR (8-week LOR, odds ratio (OR) = 1.18, 95% confidence interval (CI):1.07– 1.32 and OR = 0.84, 0.76– 0.94; 12-week LOR, OR = 1.12, 95% CI:1.02– 1.24 and OR = 0.89, 95% CI:0.81– 0.98). ROC curves showed that both phenotypic age and age gap had acceptable performance in predicting 8-week and 12-week LOR (the area under the curve (AUC) was 0.739– 0.784).Conclusion: Phenotypic age is associated with LOR to biological agent in patients with CD, and has acceptable performance in predicting 8-week and 12-week LOR.Keywords: Crohn’s disease, biologic agent, biological age, loss of response