Causes of Treatment Failure in Children With Inflammatory Bowel Disease Treated With Infliximab

Naviglio, Samuele; Lacorte, Doriana; Lucafò, Marianna; Cifù, Adriana; Favretto, Diego; Cuzzoni, Eva; Silvestri, Tania; Mucelli, Martina Pozzi; Radillo, Oriano; Decorti, Giuliana; Fabris, Martina; Bramuzzo, Matteo; Taddio, Andrea; Stocco, Gabriele; Alvisi, Patrizia; Ventura, Alessandro; Martelossi, Stefano

doi:10.1097/mpg.0000000000002112

Cited by 40 publications

(37 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, the variability of infliximab response among different age groups may be related to pharmacokinetic factors dependent also on anthropometric parameters. 15 Indeed, weight and body surface can influence infliximab clearance and serum concentrations, which correlate with the possibility of clinical and endoscopic remission [16][17][18] and the loss of efficacy during maintenance. 19 The dosing of infliximab is weight based, but the correlation between infliximab clearance and body weight is not linear.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of infliximab in very early onset inflammatory bowel disease: a national comparative retrospective study

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background Very few data regarding the use of infliximab in children with very early-onset inflammatory bowel disease (VEO-IBD) have been reported. Objective We aimed to assess the efficacy and the safety of infliximab in children with VEO-IBD compared with older children. Methods Children treated with infliximab were identified within the Italian IBD registry. The primary outcome was the rate of clinical remission at weeks 14 and 54. Secondary outcomes included the proportion of partial clinical response, treatment duration, and incidence of adverse events. Results Forty-two children with VEO-IBD were compared with 130 children with IBD. Despite significantly higher infliximab withdrawals in VEO-IBD patients during induction (42.9% vs 7.7% p < 0.01), remission rates at week 14 were similar (28.6% vs 43.8%, p = 0.10). At week 54 fewer VEO-IBD children were in remission (15.8% vs 54.3%, p < 0.01). The treatment duration was shorter in VEO-IBD (median 12.0 vs 18.4 months, p < 0.01). During the induction phase, adverse events were more common in the VEO-IBD group ( p < 0.01). Conclusion Compared with older children, VEO-IBD patients have higher rates of infliximab failures, lower remission rates at one year, and more often experience adverse events during induction.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of infliximab in very early onset inflammatory bowel disease: a national comparative retrospective study

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Higher concentrations of adalimumab and infliximab in serum have been reported to correlate with clinical response not only in adults with RA, but also in adults with psoriasis [16] or IBD [17]. Several studies have been published on children with IBD receiving anti-TNF drug treatment showing a relationship between trough levels and disease activity [18,19]. The therapeutic range is a pharmacologic term for the concentration range that provides efficacy without resulting in unacceptable toxicity [20,21].…”

Section: Introductionmentioning

confidence: 99%

“…Studies in adults with inflammatory bowel disease (IBD) have described a therapeutic drug range of 3-7 μg/mL for infliximab [25]. In a recently published observational study of Naviglio et al in children with IBD, infliximab concentrations > 3.11 μg/mL predicted sustained clinical remission and most cases of therapeutic failure were associated with low serum drug levels [19].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic drug monitoring of anti-TNF drugs: an overview of applicability in daily clinical practice in the era of treatment with biologics in juvenile idiopathic arthritis (JIA)

et al. 2021

View full text Add to dashboard Cite

Background Anti-tumor necrosis factor (TNF) drugs have improved the prognosis for juvenile idiopathic arthritis (JIA) significantly. However, evidence for individual treatment decisions based on serum anti-TNF drug levels and the presence of anti-drug antibodies (ADAbs) in children is scarce. We aimed to assess if anti-TNF drug levels and/or ADAbs influenced physician’s treatment decisions in children with JIA. Methods Patients’ records in our center were retrospectively screened for measurements of anti-TNF drug levels and ADAbs in children with JIA using etanercept, adalimumab or infliximab. Clinical characteristics and disease activity were retrieved from patient charts. Results We analyzed 142 measurements of anti-TNF drug levels in 65 children with JIA. Of these, ninety-seven (68.3%) were trough concentrations. N = 14/97 (14.4%) of these showed trough concentrations within the therapeutic drug range known for adults with RA and IBD. ADAbs against adalimumab were detected in seven patients and against infliximab in one patient. Seven (87,5%) of these ADAb-positive patients had non-detectable drug levels. A flowchart was made on decisions including rational dose escalation, stopping treatment in the presence of ADAbs and undetectable drug levels, showing that 45% of measurements influenced treatment decisions, which concerned 65% of patients (n = 42/65). Conclusions In the majority of patients, measurement of anti-TNF drug levels led to changes in treatment. A wide variation of anti-TNF drug levels was found possibly due to differences in drug clearance in different age groups. There is need for determination of therapeutic drug ranges and pharmacokinetic curves for anti-TNF and other biologics in children with JIA.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

Causes of Treatment Failure in Children With Inflammatory Bowel Disease Treated With Infliximab

Cited by 40 publications

References 26 publications

Efficacy and safety of infliximab in very early onset inflammatory bowel disease: a national comparative retrospective study

Efficacy and safety of infliximab in very early onset inflammatory bowel disease: a national comparative retrospective study

Therapeutic drug monitoring of anti-TNF drugs: an overview of applicability in daily clinical practice in the era of treatment with biologics in juvenile idiopathic arthritis (JIA)

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

Contact Info

Product

Resources

About