Infliximab and adalimumab drug levels in Crohn's disease: contrasting associations with disease activity and influencing factors

M. G. Ward*, B. Warner, N. Unsworth, S. W. Chuah, C. Brownclarke, S. Shieh, M. Parkes, J. D. Sanderson, Z. Arkir, J. Reynolds, P. R. Gibson, P. M. Irving

*Corresponding author for this work

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57 Citations (Scopus)

Abstract

Background: Discriminative drug level thresholds for disease activity endpoints in patients with Crohn's disease. have been consistently demonstrated with infliximab, but not adalimumab. Aims: To identify thresh

Background

Discriminative drug level thresholds for disease activity endpoints in patients with Crohn's disease. have been consistently demonstrated with infliximab, but not adalimumab.

Aims

To identify threshold concentrations for infliximab and adalimumab in Crohn's disease according to different disease endpoints, and factors that influence drug levels.

Methods

We performed a cross‐sectional service evaluation of patients receiving maintenance infliximab or adalimumab for Crohn's disease. Serum drug levels were at trough for infliximab and at any time point for adalimumab. Endpoints included Harvey‐Bradshaw index, C‐reactive protein and faecal calprotectin. 6‐tioguanine nucleotide (TGN ) concentrations were measured in patients treated with thiopurines.

Results

A total of 191 patients (96 infliximab, 95 adalimumab) were included. Differences in infliximab levels were observed for clinical (=.081) and biochemical remission (=.003) and faecal calprotectin normalisation (<.0001) with corresponding thresholds identified on ROC analysis of 1.5, 3.4 and 5.7 μg/mL . Adalimumab levels were similar between active disease and remission regardless of the endpoint assessed. Modelling identified that higher infliximab dose, body mass index and colonic disease independently accounted for 31% of the variation in infliximab levels, and weekly dosing, albumin and weight accounted for 23% of variation in adalimumab levels. TGN levels did not correlate with drug levels.

Conclusions

Infliximab drug levels are associated with the depth of response/remission in patients with Crohn's disease, but no such relationship was observed for adalimumab. More data are needed to explain the variation in drug levels.ld concentrations for infliximab and adalimumab in Crohn's disease according to different disease endpoints, and factors that influence drug levels. Methods: We performed a cross-sectional service evaluation of patients receiving maintenance infliximab or adalimumab for Crohn's disease. Serum drug levels were at trough for infliximab and at any time point for adalimumab. Endpoints included Harvey-Bradshaw index, C-reactive protein and faecal calprotectin. 6-tioguanine nucleotide (TGN) concentrations were measured in patients treated with thiopurines. Results: A total of 191 patients (96 infliximab, 95 adalimumab) were included. Differences in infliximab levels were observed for clinical (P=.081) and biochemical remission (P=.003) and faecal calprotectin normalisation (P<.0001) with corresponding thresholds identified on ROC analysis of 1.5, 3.4 and 5.7 μg/mL. Adalimumab levels were similar between active disease and remission regardless of the endpoint assessed. Modelling identified that higher infliximab dose, body mass index and colonic disease independently accounted for 31% of the variation in infliximab levels, and weekly dosing, albumin and weight accounted for 23% of variation in adalimumab levels. TGN levels did not correlate with drug levels. Conclusions: Infliximab drug levels are associated with the depth of response/remission in patients with Crohn's disease, but no such relationship was observed for adalimumab. More data are needed to explain the variation in drug levels.

Original languageEnglish
Pages (from-to)150-161
Number of pages12
JournalAlimentary Pharmacology and Therapeutics
Volume46
Issue number2
Early online date8 May 2017
DOIs
Publication statusPublished - Jul 2017

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