Association of golimumab trough concentrations during maintenance with clinical, biological, endoscopic and histologic remission in patients with ulcerative colitis

Abstract

Background: Optimal golimumab concentration thresholds for important outcomes during maintenance are lacking.

Aims: To investigate the association of golimumab trough concentrations during maintenance with key outcomes, including endoscopic and histologic remission, and long-term event-free persistence with golimumab, in patients with UC.

Methods: This multi-centre, cross-sectional study included patients with UC on golimumab maintenance recruited either in remission or during a flare. Colonoscopy was scheduled, and study-specific rectocolonic biopsies were taken for blind central histologic reading. Samples for golimumab trough concentrations were collected close to colonoscopy.

Results: Fifty-two patients were included. Median golimumab trough concentrations (μg/ml) were significantly higher in patients who had clinical remission (2.01 vs. 0.72, p = 0.047), combined clinical-biochemical remission (PMS ≤2 + faecal calprotectin <250 μg/g) (2.21 vs. 1.47, p = 0.041), endoscopic healing (Mayo endoscopic subscore 0) (2.52 vs. 1.47, p = 0.003), histologic remission (Geboes index ≤2.0) (2.33 vs. 1.50, p = 0.02) and disease clearance (clinical remission endoscopic healing + histologic remission) (2.52 vs. 1.70, p = 0.009), compared with those not meeting these criteria. Golimumab concentrations were significantly higher in patients who avoided golimumab dose escalation/discontinuation during follow-up (2.24 vs. 0.98, p = 0.012). Receiver-operating characteristic analyses identified golimumab thresholds [area under the curve] of 0.85 [0.76], 1.90 [0.76], 2.29 [0.75], 1.79 [0.68], 2.29 [0.72] and 1.56 [0.71] μg/ml as associated with clinical remission, combined remission, endoscopic healing, histologic remission, disease clearance and long-term event-free persistence with golimumab, respectively.

Conclusions: Golimumab trough concentrations during maintenance are associated with favourable treatment outcomes including endoscopic healing, histologic remission and long-term persistence on golimumab. We identified the optimal golimumab thresholds most closely associated with key outcomes.

Keywords: disease clearance; endoscopic healing; golimumab; histologic remission; pharmacokinetic; therapeutic drug monitoring; ulcerative colitis.