Dynamics of serum concentrations of antibodies to infliximab: a new approach for predicting secondary loss of response in inflammatory bowel diseases

Grasmeier, Melina K.; A, Langmann; Langmann, Peter; Treiber, Matthias; Thaler, Markus; Luppa, Peter B.

doi:10.1177/17562848211037849

Cited by 4 publications

(1 citation statement)

References 44 publications

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“…[ 65 ] This drug titration to a target trough level may minimize subtherapeutic and supratherapeutic doses, thus reducing the risk of ADA development and adverse side effects, respectively. [ 77 78 79 ] Furthermore, proactive TDM may be used to guide the de-escalation of biologics in patients with supratherapeutic drug concentration[ 76 80 ] This can be accomplished by dose reduction or increased time intervals, both of which may potentially decrease the cost of TDM. [ 21 23 81 ] Additional cost reductions associated with proactive TDM have also been reported in the literature as a result of remission and fewer hospitalizations/surgeries.…”

Section: Proactive Therapeutic Drug Monitoringmentioning

confidence: 99%

Therapeutic drug monitoring for biological medications in inflammatory bowel disease

Cogan

El-Matary

2022

Saudi Journal of Gastroenterology

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Therapeutic drug monitoring (TDM) is the measurement of serum drug concentrations and anti-drug-antibodies (ADA) for biologic therapies used to treat inflammatory bowel disease (IBD). The aim of this article is to review the current literature concerning reactive and proactive TDM for both adults and children with IBD. Although optimal trough concentration windows for some of these medications are not well defined, there is mounting evidence to suggest that reactive TDM is associated with favorable therapeutic outcomes, including less immunogenicity, greater drug exposure, and a decreased risk of treatment failure. Moreover, while the exact mechanism of loss of response is not fully elucidated, the vast majority of studies have reported a decreased incidence of nonresponse and secondary loss of response when TDM is implemented. Proactive TDM, while even less understood in the literature, employs a schedule of preemptive analysis of serum trough concentrations to accordingly adjust the patient's biologic dosage. Proactive TDM may decrease the need for IBD-related surgery/hospitalization, and therefore merits future studies of investigation.

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Section: Proactive Therapeutic Drug Monitoringmentioning

confidence: 99%

Therapeutic drug monitoring for biological medications in inflammatory bowel disease

Cogan

El-Matary

2022

Saudi Journal of Gastroenterology

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HLA-DQA1*05 correlates with increased risk of anti-drug antibody development and reduced response to infliximab in Chinese patients with Crohn’s disease

Wang,

Zhang,

Zhao

et al. 2023

Gastroenterology Report

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Background The efficacy of anti-TNF therapy in Crohn’s disease (CD), such as infliximab, is often compromised by the development of anti-drug antibodies (ADAs). The genetic variation HLA-DQA1*05 has been linked to the immunogenicity of biologics, influencing ADA formation. This study investigates the correlation between HLA-DQA1*05 and ADA formation in CD patients treated with infliximab in a Chinese Han population and assesses clinical outcomes. Methods In this retrospective cohort study, 345 infliximab-exposed CD patients were genotyped for HLADQ A1*05A>G (rs2097432). We evaluated the risk of ADA development, loss of infliximab response, adverse events, and treatment discontinuation among variant and wild-type allele individuals. Results A higher percentage of patients with ADAs formation was observed in HLA-DQA1*05 G variant carriers compared with HLA-DQA1*05 wild-type carriers (58.5% vs 42.9%, P = 0.004). HLA-DQA1*05 carriage significantly increased the risk of ADAs development (adjusted hazard ratio = 1.65, 95% CI 1.18–2.30, P = 0.003) and was associated with a greater likelihood of infliximab response loss (adjusted HR = 2.55, 95% CI 1.78–3.68, P < 0.0001) and treatment discontinuation (adjusted HR = 2.21, 95% CI 1.59–3.06, P < 0.0001). Interestingly, combined therapy with immunomodulators increased the risk of response loss in HLA-DQA1*05 variant carriers. Conclusions HLA-DQA1*05 significantly predicts ADAs formation and impacts treatment outcomes in infliximab-treated CD patients. Pre-treatment screening for this genetic factor could therefore be instrumental in personalizing anti-TNF therapy strategies for these patients.

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Surface plasmon resonance assays for the therapeutic drug monitoring of infliximab indicate clinical relevance of anti-infliximab antibody binding properties

Grasmeier

Weber

Treiber

et al. 2023

Clinical Chemistry and Laboratory Medicine (CCLM)

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Objectives The therapeutic antibody infliximab (IFX) has improved the life quality of numerous autoinflammatory disease patients. However, IFX can trigger the generation of anti-drug antibodies (ADA), whose optimal evaluation and management are currently subject of controversial discussions. We present two novel surface plasmon resonance (SPR) biosensor assays for therapeutic drug monitoring of IFX and characterization of ADA and investigated the diagnostic value of ADA binding properties. Methods IFX and ADA were quantified via developed SPR biosensor assays (IFXmon and ADAmon, respectively) and diagnostics-approved ELISA in sera from inflammatory bowel disease patients. Pre-analytic ADA enrichment with magnetic beads enabled analytical drug tolerance of the ADAmon assay. The dissociation ratio (DissR) as an index for ADA:IFX binding stability was calculated from the SPR sensorgrams of ADA quantification runs. Results IFX levels determined by IFXmon assay and ELISA showed high agreement, whereas ADA quantification concordance between ADAmon assay and ELISA was poor. In patients, DissR was predominantly constant over time and differed significantly between therapy outcomes. A DissR cut-off of 1.524 indicated undetectable IFX levels with 71.4% sensitivity and 88.9% specificity. Additionally, the SPR reference surface was exploited as serum-individual negative control to check result plausibility within multi-sample run sequences. Conclusions Overall, both SPR biosensor assays exhibited reliable quantitative performance with accuracies superior to their ELISA counterparts and precision inferior to ELISA only for ADAmon. DissR presented itself as promising ADA binding parameter and could contribute to both earlier and more tailored therapeutic decisions.

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Dynamics of serum concentrations of antibodies to infliximab: a new approach for predicting secondary loss of response in inflammatory bowel diseases

Cited by 4 publications

References 44 publications

Therapeutic drug monitoring for biological medications in inflammatory bowel disease

Therapeutic drug monitoring for biological medications in inflammatory bowel disease

HLA-DQA1*05 correlates with increased risk of anti-drug antibody development and reduced response to infliximab in Chinese patients with Crohn’s disease

Surface plasmon resonance assays for the therapeutic drug monitoring of infliximab indicate clinical relevance of anti-infliximab antibody binding properties

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