Vedolizumab (VDZ) is a monoclonal antibody which targets a4b7 integrin. It has been demonstrated to have efficacy in the induction and maintenance of remission in patients with both ulcerative colitis (UC) and Crohn’s disease (CD). We aimed to determine factors, including drug levels, associated with success of VDZ induction therapy.
Patients were recruited prospectively from three Irish Academic Medical Centres. Individuals were included if >18 years, with an established diagnosis of UC or CD and due to commence VDZ therapy. Disease activity scores were assessed on day of infusion (week 0) and again at week 14. All patients received standard per protocol VDZ induction therapy for UC and CD. Serum samples for trough VDZ level assessment were collected prior to week 2 and 6 VDZ infusions. The primary endpoint was steroid-free remission following VDZ induction assessed at week 14. Steroid free remission was defined as the absence of corticosteroid use and a partial mayo score ≤ 1 (for UC patients) or HBI < 5 (for CD patients). All continuous data are presented as median (range). p-value of <0.05 was considered significant in all analyses.
Forty-four patients were recruited of whom n = 40 had available follow-up to week 14 [median age at study entry was 51.95 (18.2–75.8); 55% of cohort had CD]. Concomitant immunomodulator use and corticosteroid use at VDZ initiation was 22% and 20% respectively. 70% had prior biologic exposure. Baseline partial Mayo score at study entry was 4 (2––6) while baseline HBI was 7 (1––20). Baseline CRP was 3.6 mg / L (1––43), albumin 41 g / L (30––52) and faecal calprotectin 764 (16.4––1250). Week 2 and week 6 trough VDZ concentrations were 25.1 μg/ml (0––56) and 20.2 μg/ml (0––66), respectively. Eighteen patients (45%) were in steroid free remission after induction at week 14. There was an association between increased week 6 trough VDZ levels and steroid free remission at week 14, p = 0.015. There was no association between week 2 trough VDZ levels and therapy outcome. Receiver operating characteristics curve was plotted for Week 6 VDZ levels with the area under the curve (95% confidence interval) being 0.742 (0.572––0.912). A cut off VDZ level of <16.7 µg/ml gave a sensitivity of 80% and specificity of 63%. An elevated baseline CRP (>5mg/L) was significantly associated with and absence of steroid free remission at week 14, p = 0.001.
Early vedolizumab trough levels are associated with steroid free remission following induction therapy. Vedolizumab therapeutic monitoring may have value in a clinical setting, however, further prospective studies and clinical validation is required.