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

Ohem, Jan; Hradský, Ondřej; Zárubová, Kristýna; Copova, Ivana; Bukovska, Petra; Průša, Richard; Malíčková, Karin; Bronský, Jiří

doi:10.1159/000477962

Cited by 11 publications

(13 citation statements)

References 35 publications

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“…In multivariate analysis, our data showed YP tended to develop ATIs more frequently than OP. In line with other studies in PIBD [3,6,13,14,24], a positive association between IFX trough levels and shorter interval length was found. As expected, within our cohort of PIBD patients, ATI positivity was associated with lower IFX trough levels.…”

Section: Discussionsupporting

confidence: 92%

Infliximab in young paediatric IBD patients: it is all about the dosing

et al. 2020

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Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients < 10 years. TDM data were collected retrospectively in 14 centres. Children treated with IFX were included if IFX was started as IBD treatment at age < 10 years (young patients, YP) and PK data were available. Older IBD patients aged 10–18 years were used as controls (older patients, OP). Two hundred and fifteen paediatric inflammatory bowel disease (PIBD) patients were eligible for the study (110 < 10 year; 105 ≥ 10 years). Median age was 8.3 years (IQR 6.9–8.9) in YP compared with 14.3 years (IQR 12.8–15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 μg/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0–12.9) vs. OP; 5.5 mg/kg (IQR 5.0–9.3); p < 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI − 1.2 to − 1.01); p < 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP; p = 0.56).Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years. What is Known? •Infliximab trough levels of paediatric IBD patients are influenced by several factors as dosing scheme, antibodies and inflammatory markers.•In 4.5–30% of the paediatric IBD patients, infliximab treatment was stopped within the first year. What is New? •The majority of young PIBD (< 10 years) have inadequate IFX trough levels at the start of maintenance treatment.•Young PIBD patients (< 10 years) were in need of a more intensive treatment regimen compared with older paediatric patients during 1 year of IFX treatment.•The chance to develop antibodies to infliximab was relatively higher in young PIBD patients (< 10 years).

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Section: Discussionsupporting

confidence: 92%

Infliximab in young paediatric IBD patients: it is all about the dosing

et al. 2020

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“…Faecal calprotectin, blood parameters such as C‐reactive protein and albumin, and, in particular, trough serum anti‐TNF levels are the most relevant 7,8 . Thus, the paediatric population has proven to be similar to the adult population in terms of the inverse correlation between serum infliximab trough levels and disease activity, as measured in terms of C‐reactive protein and faecal calprotectin 9–11 . The same association between trough serum infliximab levels and response was observed for adalimumab 12 .…”

Section: Introductionmentioning

confidence: 80%

Pharmacogenetics of trough serum anti‐TNF levels in paediatric inflammatory bowel disease

Salvador-Martín

Pujol-Muncunill

Bossacoma

et al. 2020

Brit J Clinical Pharma

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Aims Identifying DNA variants associated with trough serum anti‐tumour necrosis factor (TNF) levels could predict response to treatment in inflammatory bowel disease (IBD). To date, no specific studies have been performed in children. The aim of this study was to identify genetic variants associated with trough serum anti‐TNF levels and whether these variants are differential markers for infliximab and adalimumab. Methods We included 154 children (age < 18 years) from 17 hospitals who had been diagnosed with IBD and actively treated with infliximab or adalimumab. Twenty‐one polymorphisms were genotyped using real‐time PCR. Trough serum anti‐TNF levels were measured using enzyme‐linked immunosorbent assay (ELISA). The association between DNA polymorphisms and the therapeutic range or the absolute values of anti‐TNF drugs was analysed by Fisher exact test, student's t‐test and logistic regression. Results The variants rs5030728 (TLR4) and rs11465996 (LY96) were associated with subtherapeutic infliximab levels. rs1816702 (TLR2) was associated with supratherapeutic levels and rs3397 (TNFRSF1B) with subtherapeutic levels of adalimumab (P < .05). In addition, rs1816702 (TLR2) and rs2569190 (CD14) were associated with absolute values of trough serum adalimumab, and rs2569190 (CD14) was associated with absolute values of trough serum adalimumab and infliximab (P < .05). Conclusion Genotyping of these DNA variants before starting treatment may help to select the best anti‐TNF drug in paediatric patients. The SNP rs1816702 is the most promising marker for tailoring the anti‐TNF regimen in children with IBD. For the first time, DNA variants are associated with trough serum anti‐TNF levels.

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“…However, no association was found between Alb level and the serum IFX level in this study, and Alb was not included as one of the candidate hematological parameters. Ohem et al 32. showed that higher CRP and ESR levels were found in pediatric patients with lower IFX TLs.…”

Section: Discussionmentioning

confidence: 98%

“…Median serum IFX levels of 17.6 μg/mL during interventional treatment and 3.55 μg/mL during maintenance therapy were determined from a study of pediatric patients 35. In a model that used CRP level <0.5 mg/dL as the definition of laboratory remission, the optimal IFX TL was 3.5 μg/mL 32. In this study, serum IFX level of 9.82 μg/mL was required to maintain a CRP level at below 0.5 mg/dL in induction therapy.…”

Section: Discussionmentioning

confidence: 99%

Serum Infliximab Cutoff trough Level Values for Maintaining Hematological Remission in Pediatric Inflammatory Bowel Disease

2019

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Background/AimsInfliximab (IFX) often loses its therapeutic effect in initial responders with inflammatory bowel disease (IBD) over time. Low serum IFX trough levels (TLs) are linked to poor clinical response and outcomes. Maintenance of optimal therapeutic IFX concentrations is important for sustaining response and achieving good clinical outcomes. Measurement of serum IFX TLs is helpful for determining a further proper therapeutic plan. However, adequate therapeutic IFX TLs in pediatric IBD is uncertain. We aimed to identify the cutoff values for IFX TLs associated with laboratory response to IFX maintenance therapy.MethodsPatients with pediatric IBD who had received IFX infusions between December 2008 and March 2015 at Samsung Medical Center were retrospectively investigated. We analyzed 239 blood samples that were collected from 103 pediatric patients. We measured IFX TLs at induction (6 and 14 weeks) and during maintenance therapy (>22 weeks, 8 weeks interval) by fluid-phase radioimmunoassays.ResultsA significant association was found between the erythrocyte sedimentation rate (ESR) and IFX TLs during maintenance (correlation coefficient, −0.11; p=0.0005). A cutoff value of 18 mm/hr for ESR was used to define higher levels. Receiver operating characteristic analysis identified optimal cutoff values: IFX TL >1.58 μg/mL (sensitivity 82% and specificity 73%).ConclusionsCutoff values are considered a prerequisite for further investigating the clinical usefulness of measurements of IFX in patients maintained with IFX treatment.

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

Cited by 11 publications

References 35 publications

Infliximab in young paediatric IBD patients: it is all about the dosing

Infliximab in young paediatric IBD patients: it is all about the dosing

Pharmacogenetics of trough serum anti‐TNF levels in paediatric inflammatory bowel disease

Serum Infliximab Cutoff trough Level Values for Maintaining Hematological Remission in Pediatric Inflammatory Bowel Disease

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