P292 Association of golimumab trough concentrations during maintenance with endoscopic and histologic remission in patients with ulcerative colitis.
Taxonera Samso, C.(1);Fernández-Aceñero, M.J.(2);Olivares, D.(1);Calvo, M.(3);Casis, B.(4);Bermejo, F.(5);López Serrano, P.(6);Iborra, M.(7);Mesonero, F.(8);Boscá Watts, M.(9);Díaz del Arco, C.(2);Vera, I.(3);Olivares, S.(4);Alba, C.(1);
(1)Hospital Clínico San Carlos, IBD Unit- Department of Gastroenterology, Madrid, Spain;(2)Hospital Clínico San Carlos, Pathology, Madrid, Spain;(3)Hospital Universitario Puerta de Hierro, Gastroenterology, Madrid, Spain;(4)Hospital Universitario 12 de Octubre, Gastroenterology, Madrid, Spain;(5)Hospital Universitario Fuenlabrada, Gastroenterology, Madrid, Spain;(6)Hospital Universitario Fundación Alcorcón, Gastroenterology, Madrid, Spain;(7)Hospital Universitario La Fe, Gastroenterology, Valencia, Spain;(8)Hospital Universitario Ramón y Cajal, Hospital Universitario Ramón y Cajal, Madrid, Spain;(9)Hospital Clínico Universitario de Valencia, Gastroenterology, Valencia, Spain;
The aim of this study was to investigate the association of serum golimumab concentrations (SGC) during maintenance therapy in UC with clinical outcomes including endoscopic and histologic healing.
This multicentre, cross-sectional cohort study included UC patients who had received at least 5 maintenance doses of golimumab. A colonoscopy was scheduled, and study-specific recto-colonic biopsies were taken for blind central histologic reading. Samples for trough SGC and anti-golimumab antibodies (AGA) were collected on the day of the scheduled golimumab administration closest to the colonoscopy. Definitions: clinical remission = partial Mayo score (PMS) ≤2 with no individual subscore >1, combined clinical-biochemical remission = PMS ≤2 + faecal calprotectin <300 μg/g, endoscopic healing = Mayo endoscopic subscore of 0, deep remission = clinical remission + endoscopic healing, histologic remission = Geboes index ≤2.0, and disease clearance = clinical remission + endoscopic healing + histologic remission.
Fifty-two patients were included. The overall median SGC was 1.79 µg/ml (interquartile range [IQR] 0.87-2.79). Three patients (5.7%) had undetectable SGC together with positive AGA. With a median of 23 [IQR 15-32] months of golimumab therapy, 46 patients (88%) were in clinical remission, 26 (52%) had combined clinical-biochemical remission, 18 patients (35%) had both endoscopic healing and deep remission, 21 (40%) had histologic remission, and 14 (27%) had disease clearance. Median SGC were significantly higher in patients who were in clinical remission (2.01 versus 0.72 µg/mL, P=0.047) µg/mL, combined clinical-biochemical remission (2.21 versus 1.47 µg/mL, P=0.041), mucosal healing and deep remission (2.52 versus 1.47 µg/mL, P=0.003), histologic remission (2.33 versus 1.50 µg/mL, P=0.02), and disease clearance (2.52 versus 1.70 µg/mL, P=0.009), compared with those not meeting these criteria. (Figure 1) The higher SGC quartiles were associated with higher rates of mucosal healing (P=0.005), and histologic remission (P=0.006). (Figure 2) Receiver-operating characteristic analyses identified SGC thresholds [area under the curve] of 0.85 [0.76], 1.90 [0.65], 2.29 [0.75], and 2.29 [0.72] µg/mL be associated with clinical remission, combined remission, deep remission, and disease clearance, respectively. (Table 1) On multivariate analysis, body mass index (P=0.021) and CRP level (P=0.040) were linearly associated with lower SGC, and concomitant immunosuppressant with higher SGC (P=0.47). (Table 2)
We identified SGC thresholds during maintenance most closely associated with clinical outcomes including endoscopic and histologic healing. Higher SGC are needed to achieve increasingly stringent therapeutic targets.