Actual Anti-TNF Trough Levels Relate to Serum IL-10 in Drug-Responding Patients With Crohn’s Disease

Abstract

Background Patients with Crohn’s disease (CD) responding to anti–tumor necrosis factor (anti-TNF) show great variability in serum drug levels, even within the therapeutic range. We aimed at exploring the role of inflammatory, genetic, and bacterial variables in relation to anti-TNF through levels in CD patients. Methods Consecutive CD patients receiving stable doses of infliximab or adalimumab were included. Clinical and analytical parameters were recorded. Cytokine response, bacterial DNA translocation, and several immune-related genes’ genotypes were evaluated, along with serum through anti-TNF drug levels. A linear regression analysis controlled by weight and drug regimen was performed. Results One hundred nineteen patients were initially considered. Five patients on infliximab and 2 on adalimumab showed antidrug antibodies in serum and were excluded. One hundred twelve patients were finally included (62 on infliximab, 50 on adalimumab). Fourteen patients on infliximab and 15 on adalimumab (22.6% vs 30%, P = 0.37) were receiving an intensified drug regimen. C-reactive protein (CRP), fecal calprotectin, Crohn’s Disease Activity Index, leukocyte count, and albumin levels in plasma were not significantly associated with infliximab or adalimumab levels in the multivariate analysis. Serum interleukin-10 (IL-10) levels were directly related to infliximab (Beta = 0.097, P < 0.0001) and adalimumab levels (Beta = 0.069, P = 0.0241). The best multivariate regression model explaining the variability of serum infliximab and adalimumab levels included IL-10. Predicted drug levels by this model robustly fitted with actual drug levels (R2 = 0.841 for infliximab, R2 = 0.733 for adalimumab). Conclusion Serum IL-10 is significantly related to serum anti-TNF levels in CD patients, showing how the disposition of anti-TNF drugs is significantly influenced by the degree of immunological activation.

Systematic review: efficacy of escalated maintenance anti‐tumour necrosis factor therapy in Crohn's disease

“…Similarly, an infliximab trough level >7 μg/mL at all time points following dose escalation was associated with radiologic response ( P = 0.039) and remission ( P = 0.019) in a sub‐group analysis of the TAILORIX cohort 75 . In five studies, however, an exposure‐response relationship following treatment intensification was not observed 23,68,72‐74,76 …”

“…Thirteen studies reported on serum drug levels following dose escalation 22,23,29,45,53,54,67‐74 . Of these, seven showed significantly higher drug levels in patients on escalated anti‐TNF therapy compared to standard dosing 29,45,53,54,68‐70 .…”

“…Thirteen studies reported on serum drug levels following dose esca lation. 22,23,29,45,53,54,[67][68][69][70][71][72][73][74] Of these, seven showed significantly higher drug levels in patients on escalated anti-TNF therapy compared to standard dosing. 29,45,53,54,[68][69][70] In a prospective study 29 of 168 CD patients on maintenance adalimumab therapy, over half (65.4%) required escalation to weekly dosing.…”

“…75 In five studies, however, an exposure-response relationship following treatment intensification was not observed. 23,68,[72][73][74]76…”

A Novel Radiomics Nomogram for the Prediction of Secondary Loss of Response to Infliximab in Crohn’s Disease

“… 4 , 5 The early assessment of LOR is crucial for physicians to select a new treatment for patients with CD. Recent studies have identified that the patient and disease characteristics, drug factors, and laboratory indices, such as smoking status, 6 body mass index (BMI), 7 , 8 disease phenotype, 9 trough levels, 10 cytokines, 11 , 12 and genotype, 13 play an important role in assessing the probability of LOR, and prediction models have been developed based on these factors. 8 Endoscopic procedures are common and effective methods for evaluating LOR to IFX therapy in patients with CD.…”