Optimizing Anti-TNF-α Therapy: Serum Levels of Infliximab and Adalimumab Are Associated With Mucosal Healing in Patients With Inflammatory Bowel Diseases

Bella Ungar, Idan Levy, Yarden Yavne, Miri Yavzori, Orit Picard, Ella Fudim, Ronen Loebstein, Yehuda Chowers, Rami Eliakim, Uri Kopylov, Shomron Ben-Horin

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims: It is not clear what serum levels of anti-tumor necrosis factor are associated with reduced intestinal inflammation in patients with inflammatory bowel disease (IBD). We aimed to identify serum levels of infliximab and adalimumab associated with mucosal healing in patients with IBD and to evaluate the putative gain in control of inflammation by incremental increases in drug levels. Methods: We performed a retrospective cross-sectional study of 145 patients with IBD treated with infliximab (n = 78) or adalimumab (n = 67) at a medical center in Israel from 2009 through 2014. We collected data from colonoscopy examinations; mucosal healing was defined as simple endoscopic score of <3 or a Mayo score ≤1. These data were compared with serum levels of anti-tumor necrosis factor agents, clinical scores, and levels of C-reactive protein. Results: Median serum levels of infliximab and adalimumab were significantly higher in patients with mucosal healing than patients with active disease (based on endoscopy) (for infliximab, 4.3 vs 1.7 μg/mL, P = .0002; for adalimumab, 6.2 vs 3.1 μg/mL, P = .01). Levels of infliximab above 5 μg/mL (area under the curve = 0.75; P < .0001) and levels of adalimumab above 7.1 μg/mL (area under the curve = 0.7; P = .004) identified patients with mucosal healing with 85% specificity. Increasing levels of infliximab beyond 8 μg/mL produced only minimal increases in the rate of mucosal healing, whereas the association between higher level of adalimumab and increased rate of mucosal healing reached a plateau at 12 μg/mL. In patients with measurable levels of infliximab >3 μg/mL, the presence of antibodies to infliximab was associated with a lower rate of mucosal healing compared with patients with similar drug level without antibodies (16% vs 50%, respectively; P = .003). Conclusions: In a retrospective study, we found significant association between serum levels of anti-tumor necrosis factor agents and level of mucosal healing. We propose that serum levels of 6-10 μg/mL for infliximab and 8-12 μg/mL for adalimumab are required to achieve mucosal healing in 80%-90% of patients with IBD, and that this could be considered as a "therapeutic window." Exceeding these levels produces only a negligible gain in proportion of patients with mucosal healing.

Original languageEnglish
Pages (from-to)550-557.e2
JournalClinical Gastroenterology and Hepatology
Volume14
Issue number4
DOIs
StatePublished - 1 Apr 2016

Keywords

  • Crohn's Disease
  • Pharmacokinetics
  • Response to Therapy
  • Ulcerative Colitis

Fingerprint

Dive into the research topics of 'Optimizing Anti-TNF-α Therapy: Serum Levels of Infliximab and Adalimumab Are Associated With Mucosal Healing in Patients With Inflammatory Bowel Diseases'. Together they form a unique fingerprint.

Cite this