New steps in infliximab therapeutic drug monitoring in patients with inflammatory bowel diseases

Abstract

AIMSTherapeutic drug monitoring (TDM) of infliximab (IFX) appears to be beneficial for patients with inflammatory bowel disease (IBD). However, the recommended target concentrations depend partly on the method used to quantify IFX. Since we recently developed a liquid chromatography-tandem mass spectrometry method to quantify IFX, we aimed to determine IFX trough concentrations (Cmin) associated with biological remission. METHODSWe retrospectively measured IFX Cmin in sera from 55 patients with IBD, on IFX maintenance therapy, and for whom demographic, biological and clinical data were collected from medical records. A threshold of IFX Cmin associated with biological remission (defined by C-reactive protein < 5 mg l -1 and faecal calprotectin <150 μg g -1 ) was determined using receiver operating characteristics analysis. RESULTSIFX Cmin ranged from <1 mg l -1 to 57.2 mg l -1 . IFX Cmin were higher (P = 0.038) in patients with biological remission and a cutoff of IFX Cmin set to 6.2 mg l -1 was associated with biological remission (sensitivity = 0.75, 95% confidence interval 0.58-0.75; specificity = 0.61, 95% confidence interval 0.39-0.83). CONCLUSIONLiquid chromatography-tandem mass spectrometry measurement of IFX Cmin and the determination of a new threshold of IFX Cmin associated with biological remission are new steps towards IFX treatment personalization in patients with IBD. British Journal of Clinical PharmacologyBr J Clin Pharmacol (2019) 85 722-728 722

Personalized Medicine of Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacogenetics, Therapeutic Drug Monitoring, and Beyond

“…However, the validation of LC-MS methods for infliximab, adalimumab ( Jourdil et al, 2018 ; El Amrani et al, 2019 ), and vedolizumab ( Schulze et al, 2018 ) returned findings significantly correlated with those obtained with ELISA immunoassays. Interestingly, the application of an LC-MS method to infliximab TDM gave a plasma concentration threshold of 6.2 mg/L for biological remission (plasma CRP<5 mg/L and FCP<150 μg/g stools) of the disease ( Nemoz et al, 2019 ), a value that was in the lower band of the therapeutic range suggested for mucosal healing in the maintenance period ( Ungar et al, 2016 ; Yarur et al, 2017 ). In another trial, an LC-MS method did monitor trough levels of vedolizumab in IBD patients ( Schulze et al, 2018 ).…”

Evaluation of Proactive Therapeutic Drug Monitoring Application in Infliximab Users in Ulcerative Colitis

“…This monoclonal antibody plays an important role in treatment, as it is indicated to reduce signs and symptoms, to induce and maintain clinical remission and mucosal healing, to reduce or discontinue corticosteroid administration and to reduce hospitalizations. 4 However, the pharmacokinetics of these agents and their immunogenicity imply a loss of response over time, due to the reduction of therapeutic levels of the drug, in addition to the appearance of neutralizing antibodies against the drug. Thus, it was analyzed that higher concentrations of these anti-TNF agents, especially during the induction period of treatment, are associated with better long-term therapeutic responses, such as disease remission and mucosal healing.…”