Concurrent immunomodulator therapy is associated with higher adalimumab trough levels during scheduled maintenance therapy

Abstract

Introduction: Combination therapy with infliximab and immunomodulators is superior to monotherapy, resulting in better outcomes and higher trough levels of infliximab. The role of concurrent immunomodulatory therapy on adalimumab trough levels has not been adequately investigated. We evaluated the impact of concomitant immunomodulation on adalimumab trough levels in patients on scheduled maintenance therapy.Method: We conducted a prospective observational, cross-sectional study of all inflammatory bowel disease patients on maintenance therapy who had adalimumab trough levels measured between January 2013 and January 2016. Drug level and anti-drug antibody measurements were performed on sera using a solid phase assay. Pairwise comparison of means was used to compare trough levels in patients with and without concomitant immune modulator therapy.Results: In total, 79 patients were included. Twenty-three patients (29.1%) were on weekly dosing whereas 56 (70.9%) were on alternate weeks. Median adalimumab trough levels were comparable in patients with and without clinical remission (6.8 μg/ml (IQR 5.6–8.1) versus 6.7 μg/ml (IQR 3.9–8.1), respectively. Patients with an elevated faecal calprotectin >250 μg/g had lower adalimumab trough levels (median 6.7, IQR 3.9–8) compared to patients with faecal calprotectin <250 μg/g (median 7.7, IQR 6.1–8.1) though this did not achieve statistical significance (p = .062). Median adalimumab trough levels among patients on concurrent immunomodulators was 7.2 μg/ml (IQR 5.7–8.1) compared to those not on concurrent immunomodulator, 6.1 μg/ml (IQR 2.7–7.7, p = .0297).Conclusion: Adalimumab trough levels were significantly higher in patients on concurrent immunomodulators during maintenance therapy. There was a trend towards a lower adalimumab trough level in patients with elevated calprotectin.