A Systematic Review on Infliximab and Adalimumab Drug Monitoring

Silva-Ferreira, Filipa; Afonso, Joana; Pinto-Lopes, Pedro; Magro, Fernando

doi:10.1097/mib.0000000000000855

Cited by 33 publications

(26 citation statements)

References 46 publications

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“…ATIs measurement can also be performed using fluid-phase radioimmunoassay and homogeneous mobility shift assay (HMSA), which are reportedly more precise. However, a gold standard measurement method and corresponding optimal cut-off levels for each method have not yet been established [4]. …”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Infliximab Therapy in Children with Crohn's Disease Using Trough Levels Predictors

Ohem

Hradský²,

Zárubová³

et al. 2017

Dig Dis

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Background: In adults, infliximab (IFX) levels correlate with disease activity, and antibodies to IFX (ATIs) predict treatment failure. We aimed to determine the association of IFX levels and ATIs with disease activity in a paediatric population. We prospectively collected blood, stool, and clinical data from 65 patients (age 10.5-15.1 years) with Crohn's disease (CD) before IFX administration, and measured IFX trough levels, ATIs, and faecal calprotectin levels (CPT). Samples were collected during maintenance therapy. We used multivariate analysis to identify the predictors of IFX levels. Summary: Lower levels of IFX were associated with ATIs positivity (OR 0.027, 95% CI 0.009-0.077). Higher C-reactive protein (CRP) level, erythrocyte sedimentation rate, and CPT levels were found in patients with lower IFX levels. The optimal combination of sensitivity (0.5) and specificity (0.74) for disease activity was calculated for IFX levels ≥1.1 µg/mL using CRP level <5 mg/L as a marker of laboratory remission. In a model that used CPT ≤100 µg/g as the definition of remission, the optimal IFX trough level was 3.5 µg/mL. No independent association between remission and ATIs was found in our study population. However, we found an independentz association between IFX levels and serum albumin levels (OR 1.364, 95% CI 1.169-1.593), p < 0.001. Key Messages: The paediatric population was similar to adult populations in terms of the association between IFX and ATIs as well as between IFX and disease activity.

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Section: Discussionmentioning

confidence: 99%

“…Several IFX cut-off levels for predicting remission have been reported. Higher levels are associated with remission defined by low C-reactive protein (CRP) levels [4] and fistula healing [5]. According to a recent study, lower IFX levels and higher faecal calprotectin (CPT) can be used to predict relapse in adult populations [6].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Infliximab Therapy in Children with Crohn's Disease Using Trough Levels Predictors

Ohem

Hradský²,

Zárubová³

et al. 2017

Dig Dis

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“…Optimizing therapy during the induction phase so that IFX or ADM concentrations are kept above certain thresholds has proven to be associated with improved responses and better outcomes (13) in IBD. Despite their overall therapeutic efficacy, more than one-third of patients on TNF-α inhibitors show no response to induction therapy (primary nonresponders) and in up to 50% of the responders, therapy becomes ineffective over time (secondary nonresponders) (14–16).…”

Section: Why Measure Therapeutic Mabs In the Clinical Laboratorymentioning

confidence: 99%

“…Laboratory testing of patients for quantitation of the MAb concentrations in circulation and assessment of immunogenicity can help optimize therapy when a partial response or a loss of response to therapy is observed. Results from laboratory testing play an important role in patient management, considering the evidence accrued for the TNF-α inhibitor class in IBD (13, 14, 17–20). When trough levels are measured in patients who have undetectable or low concentrations of the MAb but no detectable ADAs, the physician may choose to increase the dose of the MAb in an attempt to increase the amount of the drug in circulation.…”

Section: Why Measure Therapeutic Mabs In the Clinical Laboratorymentioning

confidence: 99%

Mass Spectrometry Approaches for Identification and Quantitation of Therapeutic Monoclonal Antibodies in the Clinical Laboratory

Ladwig

Barnidge

Willrich

2017

Clin Vaccine Immunol

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Therapeutic monoclonal antibodies (MAbs) are an important class of drugs used to treat diseases ranging from autoimmune disorders to B cell lymphomas to other rare conditions thought to be untreatable in the past. Many advances have been made in the characterization of immunoglobulins as a result of pharmaceutical companies investing in technologies that allow them to better understand MAbs during the development phase. Mass spectrometry is one of the new advancements utilized extensively by pharma to analyze MAbs and is now beginning to be applied in the clinical laboratory setting. The rise in the use of therapeutic MAbs has opened up new challenges for the development of assays for monitoring this class of drugs. MAbs are larger and more complex than typical small-molecule therapeutic drugs routinely analyzed by mass spectrometry. In addition, they must be quantified in samples that contain endogenous immunoglobulins with nearly identical structures. In contrast to an enzyme-linked immunosorbent assay (ELISA) for quantifying MAbs, mass spectrometry-based assays do not rely on MAb-specific reagents such as recombinant antigens and/or anti-idiotypic antibodies, and time for development is usually shorter. Furthermore, using molecular mass as a measurement tool provides increased specificity since it is a first-order principle unique to each MAb. This enables rapid quantification of MAbs and multiplexing. This review describes how mass spectrometry can become an important tool for clinical chemists and especially immunologists, who are starting to develop assays for MAbs in the clinical laboratory and are considering mass spectrometry as a versatile platform for the task.

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“…Studies have continuously shown there is benefit in having laboratory tests to quantify mAbs as part of routine care. Concentrations of infliximab or adalimumab above certain thresholds result in improved responses to therapy and better outcomes when compared to empirical trial and error, and thus, success is keeping the patient on mAbs for as long as possible (7).…”

Section: Laboratory Reflectionsmentioning

confidence: 99%

Therapeutic Monoclonal Antibodies in the Clinical Laboratory

Willrich

2017

The Journal of Applied Laboratory Medicine

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A Systematic Review on Infliximab and Adalimumab Drug Monitoring

Abstract: Concerning drug levels monitoring any methodology is adequate. With respect to antidrug antibody levels, it will be necessary to define a gold standard method or to establish different cutoff levels for different methodologies.

Cited by 33 publications

References 46 publications

Evaluation of Infliximab Therapy in Children with Crohn's Disease Using Trough Levels Predictors

Evaluation of Infliximab Therapy in Children with Crohn's Disease Using Trough Levels Predictors

Mass Spectrometry Approaches for Identification and Quantitation of Therapeutic Monoclonal Antibodies in the Clinical Laboratory

Therapeutic Monoclonal Antibodies in the Clinical Laboratory

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