Demographic characteristics
A total of 60 patients with CD met the inclusion and exclusion criteria(See flow chart of participants and data in Supplementary Figure S1). Enrolled patient with a median age of 27 years, were enrolled in the study and all received IFX therapy. The male to female ratio was 2.75 (44:16), the median Body Mass Index(BMI) was 19.97 kg/m2, and the median duration of disease was 3.81 years. 23.3% of the patients smoked and 60% had a bachelor's degree or above. The rates of Vit-D deficiency and insufficiency were 51.67% and 40%, respectively. The main clinical symptoms were abdominal pain (60%) and diarrhea (45%), 35% of patients received IMM in combination (including 85% who received azathioprine). According to the Montreal classification, the diagnosed age was mostly A2, the affected intestinal location was mostly L3, the disease behavior was mostly B1, and 60% had perianal lesions. 28.3% of the patients had undergone intestinal surgery and 58.3% had undergone perianal surgery.The treatment efficiency was evaluated before the seventh IFX treatment. 81.7% of patients achieved clinical remission and 28.3% achieved biochemical remission. Endoscopic re-examination was performed in 42 patients, of whom 66.7% achieved endoscopic remission and 42.9% achieved endoscopic response (Table 1).
Baseline variables associated with clinical remission
Patients were divided into clinical remission(n=49) and non-remission(n=11) groups according to whether their CDAI score was <150 at the endpoint. Among the two groups, the clinical non-remission group had a higher proportion of IMM than the remission group (81.8% vs. 24.5%, P=0.001), but other demographic measures were not statistically different between the two groups(Supplementary materials).
Baseline biochemical markers(including inflammatory indicators such as C-reactive protein(CRP), erythrocyte sedimentation rate(ESR), high sensitive C-reaction protein(hsCRP), blood routine indicators, liver and kidney function, electrolyte, micronutrient indicators(including Vit-D)), TDM, ATI before the fourth IFX treatment were analyzed in both groups to identify baseline factors effect on clinical remission at week 38. The median IFX-TC was 4μg/mL in the remission group and 2.1μg/mL in the non-remission group(P=0.061). However, the positive rate of ATI in remission group was lower than that in non-remission group (6.12% vs. 36.36%, P=0.012). Baseline Vit-D levels were higher in the clinical remission group than in the non-remission group (20.92 ng/ml vs. 16.43 ng/ml, P=0.036), and median CRP and hs-CRP levels were lower (12 mg/l vs.79.4 mg/l , P=0.003; 21.71 mg/l vs. 66.55 mg/l , P=0.016) and lower median ESR level (17 mm/h vs. 42 mm/h, P=0.003) . In addition, there were statistically significant differences in red blood cell(RBC), hemoglobin(Hb), prealbumin(PA), urea nitrogen(BUN) and blood Ca between the two groups (P<0.05)(Table 2).
Above indicators were incorporated into logistic regression for multivariate regression analysis, and the results showed that Vit-D level, CRP, blood K at baseline were correlated with clinical remission(CDAI<150) at the seventh IFX treatment (P <0.05)(Table 3). Receiver operating characteristic(ROC) curve analysis showed that when Vit-D concentration was 15.81ng/ml, the diagnostic value of CDAI(=150) at endpoint was AUC 0.711 (95%CI: 0.523-0.899), the sensitivity was 81.6%, and the specificity was 63.6%(P=0.03)(Figure 1).
Subgroup association analysis of baseline variables
Different baseline variables were divided into subgroups to analyze the influencing factors of clinical remission in patients with CD. Due to the limited sample size, CDAI score was taken as the dependent variable, and significant factors in univariate analysis were included in linear regression for multi-factor analysis. When patients were grouped by gender, then RBC, Hs-CRP, and mean corpuscular volume(MCV) were independent predictors of CDAI score at the endpoint in the female subgroup, while Vit-D, ESR, and hs-CRP were independent predictors of CDAI in the male subgroup(P<0.05). Patients were divided into low body weight group and normal body weight group according to BMI. It was found that no independent predictor of CDAI was found in the low body weight group, while baseline Hb, folic acid and FBG levels in the normal body weight subgroup were independent predictors of CDAI(P<0.05). In the subgroup of smoking, ESR and blood K levels were independent factors in the smoking group, while Vit-D, BMI and CRP levels were independent factors in the non-smoking group(P<0.05). Grouped according to whether or not they had undergone intestinal surgery, Vit-D, ESR, and Hs-CRP were found to be independent predictors of CDAI in patients without intestinal surgery, while RBC and BUN levels were independent predictors of CDAI in patients with intestinal surgery(P<0.05). Grouping by perianal surgery or not, Vit-D, CRP, and course of disease were found to be independent predictors of CDAI in the non-perianal surgery group, while Vit-D, TB, blood P, and ANA levels were independent predictors in the subgroup that had perianal surgery(P<0.05). Grouping by IMM use or not, Vit-D, WBC were found to be independent predictors of CDAI in the no combined IMM group, while ESR, RBC, Hb, DB and BUN levels were independent predictors in the subgroup that had combined IMM(P<0.05)(Table 4 and Supplementary materials).
Further, ROC curve analysis was performed between the above subgroup variables and the endpoint CDAI outcomes. In the normal BMI subgroup, when Vit-D level were 16.06ng/ml, the diagnostic value of CDAI(=150) at endpoint was AUC(95%CI) 0.77(0.556~0.985), and the sensitivity and specificity were 0.82 and 0.71(P=0.029). In the no smoking and combine with IMM subgroup, when Vit-D level were 19.05ng/ml and 15.81ng/ml respectively, the diagnostic value of CDAI(=150) at endpoint was AUC(95%CI) 0.74(0.54~0.94) and 0.81(0.604~1), the sensitivity were 0.568 and 0.917 the specificity were 0.889(P=0.026)and 0.667(P=0.019)(Table 5).