Clinical Impact of Corrections to Infliximab and Adalimumab Monitoring Results with the Homogeneous Mobility Shift Assay.

Konstantinos Papamichael,Adam S Cheifetz,Sarah N Flier,William T Clarke,Joseph D Feuerstein,Katharine A Germansky,Andrea Banty,Gil Y Melmed,Valerio J Thomas

doi:10.3390/jcm9092840

Abstract

An upward drift for both infliximab and adalimumab concentrations measured by the homogenous mobility shift assay (HMSA) was previously reported. We aimed to investigate the impact of this drift on clinical care of patients with inflammatory bowel disease. This was a retrospective, multicenter study. Providers reviewed the individual patient data and drug concentrations before and after the laboratory corrections and then documented whether a different clinical decision would have been made had the corrected drug concentration been originally reported. A multivariable Cox proportional hazards regression analysis was performed to investigate the association of a documented treatment change with treatment failure, defined as drug discontinuation for primary nonresponse, loss of response, or serious adverse event, adjusting for confounding factors. The study population consisted of 479 patients (infliximab, n = 219; adalimumab, n = 260). Upon review, 14.9% (71/479) patients would have had a different treatment decision made had the corrected drug concentration been initially reported. After a median follow-up of 10.6 months, 25.7% of patients (123/479) had treatment failure. A theoretical different clinical decision based on the corrected drug concentrations was not associated with treatment failure (adjusted hazard ratio (HR): 1.452; 95% confidence interval (CI): 0.805–2.618; p = 0.216), which was consistent for both infliximab (adjusted HR: 1.977; 95% CI: 0.695–5.627; p = 0.201) and adalimumab (adjusted HR: 1.484; 95% CI: 0.721–3.054; p = 0.284). The drift in infliximab and adalimumab concentrations in the HMSA assay affected treatment decisions in 15% of cases. However, this discrepancy was not associated with a higher cumulative probability for treatment failure.

Highlights

The use of therapeutic drug monitoring (TDM) of antitumor necrosis factor therapies has become more common for the treatment of inflammatory bowel disease (IBD)
Evidence suggests that proactive TDM is associated with better therapeutic outcomes compared to empiric treatment optimization and/or reactive TDM in patients with IBD treated with either infliximab or adalimumab [2,3,4,5,6]
An upward drift for both infliximab and adalimumab concentrations measured by the homogeneous mobility shift assay (HMSA) was previously found, followed by a correction of the values that was reported to the treatment providers

Summary

Introduction

The use of therapeutic drug monitoring (TDM) of antitumor necrosis factor (anti-TNF) therapies has become more common for the treatment of inflammatory bowel disease (IBD). Physicians must decide, for example, to change therapy when a patient has active IBD despite therapeutic drug concentrations, increase drug when a patient has subtherapeutic concentrations, or de-escalate treatment when a patient is in remission and has supratherapeutic drug concentrations These thresholds can vary depending on the targeted clinical outcome, IBD phenotype, and TDM assay used [7]. Regarding the latter, we have previously shown a discrepancy between a commercially available enzyme-linked immunosorbent assay (ELISA) and a commercially available homogeneous mobility shift assay (HMSA), for both infliximab and adalimumab concentrations [8,9].

Experimental Section

Study Population

Comparison of Drug Concentrations

Discussion