The remaining authors disclose no conflicts of interest. Ethics approval The study was approved by the Sheba Medical Center ethics committee. Associations between terminal ileum and colonic thickness, adalimumab levels and therapy retention were assessed. Results Fifty events of ultrasound with concomitant adalimumab trough level measurements in 44 Crohn’s disease patients were included. Patients with trough level 3?g/ml had significantly higher bowel wall thickness, both for terminal ileum (values were two-sided, and a value less than 0.05 was considered statistically significant. All statistics were performed with MedCalc software (version 12.2.1.0, Mariakerke, Belgium). Results Demography and clinical outcomes In total, 50 IUS with concomitant prospective adalimumab trough level measurements were included in the study (obtained from 44 CD patients). Hence, six patients had two events included, all during maintenance therapy, with at least six months between events. The median time period between the IUS and trough level measurements was 13 days (IQR 6C21 days). Median age at induction was 33.5 years (IQR 25.7C39.2 years), male to female GSK-650394 ratio was 0.91. Twelve patients (27.2%) received concomitant immunomodulator therapy. Fourteen patients (32.5%) previously received anti-TNF therapy. Median time from commencement of adalimumab therapy to IUS was 10.8 months (IQR 5.7C17.5 months). The patients’ clinical and demographic characteristics are depicted in Table 1. Table 1. Patients’ demographic and clinical characteristics. GSK-650394 (%)44 (100)Age at induction, years (median, IQR)33.5 (25.7C39.2)Age at diagnosis, years (median, IQR)27 (19C36)Disease duration, years (median, IQR)2 (1C7.5)Male/female ratio0.91Smoking at induction, (%)12 (27.2)Past smoker, (%)6 (13.6)Previous surgery, (%)10 (22.7)Weight at induction (median, IQR)65 (59C82.5)Comorbidities, (%)21 (47.7)Concomitant immunomodulator therapy, (%)12 (27.2)Disease location, (%)Ileal?-?22 (50) Ileo-colonic?-?22 (50)Disease behavior, (%)Inflammatory?-?22 (50) Stricturing?-?14 (31.8) Fistulizing?-?8 (18.2)Perianal involvement, (%)12 (27.2)CD upper GI involvement, (%)12 (27.2)Extra-intestinal manifestations, (%)23 (52.2)Previous adalimumab therapy, (%)3 (6)Previous anti-TNF therapy, (%)14 (32.5)Previous immunomodulator therapy, (%)26 (60.4)Once weekly adalimumab therapy10 (20) Open in a separate window CD: Crohn’s disease; GI: gastrointestinal; IQR: interquartile range; TNF: tumor necrosis factor. aNumber of events of adalimumab measurement within 30 days of intestinal ultrasound. Association of adalimumab trough serum levels and bowel wall thickness There was a significant unfavorable association between adalimumab trough level and TI wall thickness on concurrent IUS; Patients with adalimumab levels below 3?g/ml had significantly higher TI wall thickness than patients with adalimumab levels above 3?g/ml (median TI thickness 5, 3.5?mm, IQR 3.5C7, 2C4.7?mm, respectively, em p /em ?=?0.04, Figure 1(a)). Thresholds of 1 1 and 2?g/ml were explored as well, although no statistical significant association with bowel wall thickness was detected (data not shown). Moreover, a statistically significant difference was noted also between the first (adalimumab level 3.1?l/ml) and fourth quartile ( 6.7?l/ml) of adalimumab levels (median thickness 5, GSK-650394 2.9?mm, confidence interval (CI) 4.1C7, 2C3.3?mm for first and fourth quartiles respectively, em p /em ?=?0.002), and between the first and second quartiles (median thickness for second quartile 3.45?mm, CI 3C4.7?mm, em p /em ?=?0.01, Supplementary Material Figure 1). Open in a separate window Physique 1. (a) Terminal ileum thickness was significantly higher in patients with adalimumab trough level (TL) below, rather GSK-650394 than above 3?g/ml. (b) Colonic maximal thickness was significantly higher in patients with adalimumab TL below, rather than above 3?g/ml. Comparable unfavorable association was observed for colonic wall thickness; Patients with adalimumab levels below 3?g/ml had significantly higher colonic wall thickness than patients with adalimumab levels above 3?g/ml (median colonic wall thickness 4, 2.5?mm, IQR 2.6C4.5, 2C3.5?mm, respectively, em p /em ?=?0.02, Physique 1(b)). Similarly, a statistically significant difference was noted also between the first and fourth quartile. Hence, Large Intestinal (LI) was significantly thicker among patients with adalimumab levels in the first, compared to the last quartile (median thickness 4, 2.35?mm, CI 2.9C4.5, 2C2.8?mm for first and fourth quartiles respectively, em p /em ?=?0.04). ROC curve analysis was performed to define adalimumab trough level, which is best associated with ultrasonographic transmural healing (i.e. normalization of bowel thickness). For the TI, a cut-off of 3?mm was used. Trough level? ?2?g/ml was best associated with TI wall thickness below 3?mm, but this trend did not reach statistical significance ( em p /em ?=?0.1, area under the curve (AUC) 0.63, sensitivity 33%, specificity 95%). For the colon, a trough level 3.8?g/ml was best associated with colonic wall thickness below 4?mm, defined as tissue healing threshold ( em p /em ?=?0.0001, AUC 0.812, sensitivity 85%, specificity 75%, Physique 2). Open Rabbit polyclonal to LDH-B in a separate window Physique 2. On receiver-operating characteristic (ROC) curve analysis, adalimumab trough level (TL) below 3.8?g/ml was significantly associated with colonic thickness 4?mm ( em p /em ?=?0.0001, area under the curve (AUC)=0.812, sensitivity 85%, specificity 75%). A sub-analysis was performed for the association of anti-adalimumab-antibodies.