Clinical relevance and inter-test reliability of anti-infliximab antibodies and infliximab trough levels in patients with inflammatory bowel disease

Guiotto, Cristina; Daperno, Marco; Frigerio, Francesco; Vizzini, Margherita; Cerruti, R.; Ercole, E.; Cosimato, M.; Lavagna, A.; Germano, Laura; Migliardi, Marco; Rocca, Rodolfo

doi:10.1016/j.dld.2015.10.023

Cited by 18 publications

(16 citation statements)

References 35 publications

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“…Although drug levels measured by different assays correlate and generally lead to the same therapeutic decision, there are systematic differences between measured levels . These may be overcome to a degree with better calibration against a universal standard, known concentrations of the tested drug.…”

Section: Resultsmentioning

confidence: 99%

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Mitrev¹,

Casteele

Seow³

et al. 2017

Aliment Pharmacol Ther

242

207

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Summary Background Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti‐tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines. Aim To develop evidence‐based consensus statements for TDM‐guided anti‐TNF therapy in IBD. Methods A committee of 25 Australian and international experts was assembled. The initial draft statements were produced following a systematic literature search. A modified Delphi technique was used with 3 iterations. Statements were modified according to anonymous voting and feedback at each iteration. Statements with 80% agreement without or with minor reservation were accepted. Results 22/24 statements met criteria for consensus. For anti‐TNF agents, TDM should be performed upon treatment failure, following successful induction, when contemplating a drug holiday and periodically in clinical remission only when results would change management. To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3‐8 and 5‐12 μg/mL, respectively, were deemed appropriate. The range may differ for different disease phenotypes or treatment endpoints—such as fistulising disease or to achieve mucosal healing. In treatment failure, TDM may identify mechanisms to guide subsequent decision‐making. In stable clinical response, TDM‐guided dosing may avoid future relapse. Data indicate drug‐tolerant anti‐drug antibody assays do not offer an advantage over drug‐sensitive assays. Further data are required prior to recommending TDM for non‐anti‐TNF biological agents. Conclusion Consensus statements support the role of TDM in optimising anti‐TNF agents to treat IBD, especially in situations of treatment failure.

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Section: Resultsmentioning

confidence: 99%

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Mitrev¹,

Casteele

Seow³

et al. 2017

Aliment Pharmacol Ther

242

207

View full text Add to dashboard Cite

show abstract

“…Another study in adults has revealed more frequent adverse reactions in patients with positive ATIs. In this study, no association was found between IFX levels and treatment outcomes [24]. In sum, it seems that higher IFX levels in adults are associated with better treatment outcomes.…”

Section: Discussionmentioning

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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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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“…30 35–38 Similarly, non-linear correlations (Spearman r) ranged from 0.95 to 0.97 36 39. Good correlations were also observed for adalimumab, golimumab and etanercept 38 40.…”

Section: Comparison Of Assaysmentioning

confidence: 96%

“…Agreement between two assays can be assessed graphically in a Bland–Altman plot or expressed quantitatively by calculating the intraclass correlation coefficient (ICC) 42. The ICC ranged from 0.59 to 0.98 across comparative studies and showed that there is a discrepancy in absolute concentration reported by some of the assays 30 35 36 39 43 44. In the study by Steenholdt et al 36 mean differences in infliximab concentrations of up to −3.44 μg/mL were found when an inhouse reporter gene assay was compared with the Prometheus ELISA.…”

Section: Comparison Of Assaysmentioning

confidence: 99%

Assays for measurement of TNF antagonists in practice

Casteele

2016

Frontline Gastroenterol

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Tumour necrosis factor (TNF) antagonist drug exposure is correlated with clinical, endoscopic and pathophysiological outcomes during induction and maintenance therapy. Measuring drug concentrations is therefore a useful tool when treating to target and optimising therapy. One of the main factors leading to suboptimal drug exposure is the formation of antidrug antibodies (ADAs), due to an immunogenic reaction of the immune system towards the nonself protein. The development of ADA does pose important concerns for drug efficacy and for safety as ADAs have been associated with acute infusion reactions, hypersensitivity reactions and serum sickness. Various assays exist to measure serum drug and ADA concentrations, either offered as a service in a specialised laboratory or commercially available as a kit. It is unclear how the performance of these assays relates to each other, until recently various comparative studies were carried out. The majority of these studies show that indeed a good correlation exists between the assays that measure drug, but that absolute concentrations can differ across tests. This is particularly relevant in clinical practice when a specific threshold or drug concentration range is targeted. For ADA assays, drug sensitivity or the ability of the assay to measure ADA in the presence of drug remains an important issue, especially for drugs with a higher dosing frequency. In addition, standardisation across ADA assays is difficult, making it hard to compare quantitative or semiquantitative (low/medium/high) results across assays and across studies.

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Clinical relevance and inter-test reliability of anti-infliximab antibodies and infliximab trough levels in patients with inflammatory bowel disease

Cited by 18 publications

References 35 publications

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

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

Assays for measurement of TNF antagonists in practice

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