The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease

Casteele, Niels Vande; Khanna, Reena; Levesque, Barrett G.; Stitt, Larry; Zou, Guangyong; Singh, Sharat; Lockton, Steven; Hauenstein, Scott; Ohrmund, Linda; Greenberg, Gordon R.; Rutgeerts, Paul; Gils, Ann; Sandborn, William J.; Vermeire, Séverine; Feagan, Brian G.

doi:10.1136/gutjnl-2014-307883

Cited by 251 publications

(189 citation statements)

References 37 publications

(40 reference statements)

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“…The same author performed another study in 483 adult patients in which the cut-off was calculated as 2.7 µg/mL using CRP level ≤5 mg/L as a marker of remission. In a prospective randomised controlled trial, target doses of 3-7 µg/mL were recommended; however, after dose optimization, continued concentration-based dosing was not superior to clinically based dosing [28]. …”

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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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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“…If the share was ≥ 3 the sample was positive for ATIs. IFX TL ≥ 2.8 μg/ml was considered to be therapeutic concentration of the drug during maintenance therapy in this study [10] .…”

Section: Measurement Of Pharmacokinetic Parametersmentioning

confidence: 99%

Infliximab Biosimilar (Remsima™) in Therapy of Inflammatory Bowel Diseases Patients: Experience from One Tertiary Inflammatory Bowel Diseases Centre

Kolář¹,

Ďuricová²,

Bortlík³

et al. 2017

Dig Dis

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Background: The evidence on the efficacy and safety of biosimilar infliximab (IFX) in patients with inflammatory bowel diseases (IBD) is sparse. Methods: Consecutive IBD patients visiting our centre were included. One cohort composed of prospectively followed patients who were switched from original to biosimilar IFX between January and March 2015. The second cohort included retrospectively assessed anti-tumor necrosis factor α-naïve patients who started therapy between January 2015 and January 2016. Disease activity was assessed using standard clinical indices, endoscopic evaluation, and laboratory parameters (blood count, C-reactive protein (CRP) and fecal calprotectin (FC)). Trough levels and anti-drug antibodies (ATIs) were also measured. Patients were evaluated 56 weeks (W56) after switch and at week 14 (W14) and week 46 (W46) in the naïve cohort. Results: Seventy-four IBD patients were switched to biosimilar IFX and 119 naïve patients newly initiated therapy with the preparation. Disease activity remained stable in a majority of switched patients (remission at week 0 (W0) vs. W56: 72.2 vs. 77.8%; median difference of both Harvey-Bradshaw index and Simple Clinical Colitis Activity Index between W0 and W56 was 0). When W0 and W56 were compared, no significant difference in CRP (4.3 ± 8.0 vs. 3.3 ± 3.8 mg/l; p = 0.89) and FC (135 ± 153 vs. 199 ± 225 µg/g; p = 0.17) was observed. In total, 92% of Crohn's disease (CD) and 83% of ulcerative colitis (UC) patients responded to induction therapy (W14) with biosimilar IFX. At W46, the response rate was 86% in CD and 64% in UC. Moreover, half of UC patients experienced mucosal healing at W14 and improvement of perianal disease occurred in 95% of CD at W46. In this cohort, clear steroid-sparing effect was observed. No increase in immunogenicity was found in switched patients (ATI positivity: 9.5 vs. 6.0%, p = 0.54) and the type and frequency of adverse events were comparable to the original preparation in both cohorts. Conclusion: Switching of IBD patients from original to biosimilar IFX is effective and safe.

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“…Using the homogeneous mobility shift assay (HMSA), Vande Casteele et al [52] demonstrated either an IFX concentration of [2.79 lg/ml or an ATI concentration of \3.15 U/ml was associated with remission; multivariable analysis indicated that concentrations of ATI and IFX were independent predictors of remission. HMSA, first developed by Wang et al [53], allows the detection of ATI in the presence of IFX, thereby overcoming the limitations of the ELISA method, which can only measure ATI in the absence of IFX because IFX interferes with the assay [54].…”

Section: Biomarkers Predicting Therapeutic Efficacymentioning

confidence: 97%

Molecular Analysis of Inflammatory Bowel Disease: Clinically Useful Tools for Diagnosis, Response Prediction, and Monitoring of Targeted Therapy

Jiang

2015

Mol Diagn Ther

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Biomarkers of inflammatory bowel disease (IBD) are non-invasive or minimally invasive tests for IBD diagnosis and/or prognosis as well as assessment of disease activity and response to therapy. Here, we update the current status of IBD biomarkers, including serological, fecal, and genetic (DNA and microRNA [miRNA]) biomarkers. As an update, the classical serological biomarkers, including ASCA, pANCA, anti-OmpC, anti-Cbir, anti-I2, and other anti-glycan antibodies, are discussed only briefly. Emphasis in this article is given to those that have been recently identified or extensively characterized, as well as to the clinical utilities of biomarkers, with special attention to prediction of disease complication and activity assessment, mucosal healing, and response to therapies. In particular, we discuss the utilities of blood-based biomarkers predicting therapeutic response to anti-tumor necrosis factor (TNF)-α, such as anti-anti-TNFα antibodies or anti-drug antibodies (ADA) and trough level of anti-TNFα. Fecal biomarkers, which have recently attracted substantial attention, are also discussed extensively, including the well-characterized calprotectin and lactoferrin, as well as the recently characterized M2-PK, CHI3L1, neopterin, MMP-9, and HMGB1. Genome and exome sequencing enables the discovery of a number of rare yet disease-defining IBD-susceptible genes, particularly those involved in very early onset IBD, providing rare yet extremely useful biomarkers at genetic levels for IBD diagnosis/prognosis. Finally, we briefly summarize the discovery, characterization, and potential implications of miRNA as potential IBD biomarkers.

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The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease

Cited by 251 publications

References 37 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

Infliximab Biosimilar (Remsima™) in Therapy of Inflammatory Bowel Diseases Patients: Experience from One Tertiary Inflammatory Bowel Diseases Centre

Molecular Analysis of Inflammatory Bowel Disease: Clinically Useful Tools for Diagnosis, Response Prediction, and Monitoring of Targeted Therapy

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