Post-Induction Adalimumab Concentration is Associated with Short-Term Mucosal Healing in Patients with Ulcerative Colitis

Abstract

Background and aims: Mucosal healing is associated with favourable therapeutic outcomes in patients with ulcerative colitis [UC]. We investigated whether adalimumab concentrations during induction therapy are associated with short-term mucosal healing [STMH] in UC patients.

Methods: This was a retrospective, single-centre study including consecutive UC patients treated with adalimumab from June 2005 to May 2014, who underwent an endoscopy both at baseline and after induction therapy [weeks 8-14] and at least one serum sample available at week 2 and/or week 4. STMH was defined as Mayo endoscopic sub-score of ≤1 with a baseline sub-score of ≥2. Adalimumab concentrations were evaluated using an in-house developed enzyme-linked immunosorbent assay.

Results: The study population consisted of 43 patients, the majority of whom [n = 38] were prior infliximab failures; the rest showed primary non-response [PNR, n = 5]. Twelve patients [27.9%] achieved STMH. Patients with STMH had higher adalimumab concentrations at week 4 compared to those without [10.6 vs 7.4 μg/ml, p = 0.014]. A receiver operating characteristic [ROC] analysis identified an adalimumab concentration threshold at week 4 of 9.4 μg/ml (area under the ROC curve [AUROC]: 0.778) and 7.5 μg/ml [AUROC: 0.798], after excluding patients with PNR to infliximab, to be associated with STMH. Multiple logistic regression analysis, after excluding patients with PNR to infliximab, identified adalimumab concentration ≥7.5 μg/ml at week 4 (odds ratio [OR]: 15.7; 95% confidence interval [CI]: 1.3-185; p = 0.029) and baseline endoscopic Mayo score 3 [OR: 0.13; 95% CI: 0.02-0.98; p = 0.047] as factors independently associated with STMH.

Conclusions: This study, reflecting real-life clinical practice, demonstrated that post-induction adalimumab concentrations are associated with STMH, while higher baseline mucosal inflammation is related to lack of STMH in UC.

Keywords: Adalimumab; mucosal healing; therapeutic drug monitoring; ulcerative colitis.