P552 Higher Serum Ustekinumab Levels Correlate With Higher Rates Of Steroid-Free Deep Remission And Endoscopic Healing In Patients With Inflammatory Bowel Diseases. (21st January 2022)

• Record Type: Journal Article
• Authors: Yarur, A; Ungaro, R; Jain, A; Nunex, L; Spencer, E; Bruss, A; Berens, B; Beniwal-Patel, P; Dervieux, T; Dubinsky, M
• Is Part Of: Journal of Crohn's and colitis. Volume 16(2022)Supplement 1
• Page Start: i498
• Page End: i499
• Publication Date: 2022-01-21
• Subjects: Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjab232.679
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background: Ustekinumab (UST) is currently approved for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). However, a significant number of patients either partially respond or do not benefit at all. With other biologics, this non-response has partially been explained by sub-optimal pharmacokinetics. The aim of this study was to assess the association between UST trough levels (UTL), antibodies to UST (ATU) and clinical/endoscopic disease activity. Methods: In this prospective cross-sectional study, we enrolled patients with CD or UC on maintenance doses of UST (≥6 months). We collected clinical data, UTL and ATU titers using a drug-tolerant assay, biomarker levels (c-reactive protein [CRP] and fecal calprotectin [FC]), Harvey Bradshaw Index (HBI) and simple endoscopic score (SES-CD) in CD, partial and endoscopic Mayo score (PMS and EMS) in UC. The primary outcome was deep steroid-free remission (SFDR) defined as HBI <5 in CD and PMS<2 in UC and a normal CRP/FC while off corticosteroids (prednisone or budesonide). The secondary outcome was endoscopic healing defined as an EMS≤1 in UC or SES-CD≤2. Results: 136 patients were included; 123 (90%) had CD, mean age was 43 years (SD:17), and 73 (54% were women). The median time on UST was 40 weeks (IQR: 32–78). Median UTL were 5.5 µg/mL (IQR: 3–8.8 µg/mL) and no patients had detectable ATU. There was a positive correlation between UTL and albumin (rho:0.35 [p<0.01]) and a negative correlation between UTL with body mass and CRP (rho:-0.32 [p=0.005] and rho: -0.32 [0.0002], respectively). Among the study population, 48/136 (35.2%) was in SFDR and 26 (42%) were in endoscopic remission. Patients in SFDR and in endoscopic remission had significantly higher UTL vs. that did not (6.4 µg/mL [4.6–11.7] vs. 4.8 µg/mL [2.5–7.6]; p<0.01 and 6.4 µg/mL [5–15] vs. 4.4 µg/mL [2.2–7.1], p=0.03 respectively) – Figure 1 and 2. There were no differences in UTL between those patients on monotherapy and those on combination therapy with a thiopurine or methotrexate (5.8 µg/mL [3.4–9.3] vs. 4.5 µg/mL [2.3–7.9], p=0.07). Patients with a UST ≥5.45 µg/mL had a two-fold higher chance of being in steroid-free deep remission vs. those that did not (OR:2.2 [95%CI:1.1–4.5], p=0.031). When adjusting for albumin (a surrogate marker of drug clearance), higher UTL were associated with higher rates of SFDR (OR per 1 µg/mL: 1.12 [95%CI: 1.01–1.26], p=0.034). Conclusion: Among patients with CD and UC, higher UTL were associated with better clinical and endoscopic outcomes. No patients in the cohort had developed immunogenicity. Dose-escalation, interventional studies looking into how a higher exposure-response to UST may improve rates of non-response are warranted.