Positive relationship between infliximab and adalimumab trough levels at completion of induction therapy with clinical response rates, at a tertiary referral center

Abstract

Background and AimAnti‐tumor necrosis factor alpha (TNFα) therapies have improved outcomes for patients with inflammatory bowel disease. The aim of this study was to explore the relationship between infliximab (IFX) and adalimumab (ADL) trough and antibody levels with clinical response rates at the end of induction.MethodsThis was a prospective, single‐center study. Patients were recruited from July 2015 to August 2016. Inclusion criteria were all inflammatory bowel disease patients older than 17 years who started treatment with IFX or ADL. Baseline clinical disease activity indexes were performed. Clinical response was defined as HBI ≤3 or partial Mayo score ≤4% or <30% reduction from baseline. Anti‐TNFα trough and antibody levels were measured using standard ELISA techniques.ResultsThirty‐five patients were recruited, of whom 23 had Crohn's disease and 12 had ulcerative colitis. Eighteen were treated with ADL and 17 with IFX. The mean age of the cohort was 40.3 years, 62.9% were females, 34.3% were on concomitant thiopurines, and 25.7% had prior anti‐TNFα exposure. Overall response rate was 51.4%, 33.3% for ADL and 70.6% for IFX.Mean trough levels were 12.5 μg/mL for IFX and 4.4 μg/mL for ADL. There was a clear link between higher anti‐TNFα trough levels at the end of induction with clinical response rates. For IFX, mean trough level was 16.4 μg/mL for responders versus 5.3 μg/mL for non‐responders (P = 0.026). Area under the curve for association of IFX level at induction with clinical response was 0.864 (P = 0.0001). Similar link was present between higher ADL levels with clinical response, although not statistically significant.ConclusionHigher trough levels at the end of induction are associated with improved response. Ongoing work will define optimal targets at this key timeframe.

Post-Induction High Adalimumab Drug Levels Predict Biological Remission at Week 24 in Patients With Crohn's Disease

“…In that study, drug trough levels did not differ between individuals with active CD and those with CD in remission. This contrasts with the report by a longitudinal prospective study of an association between trough levels and clinical remission ( 32 ). However, that prospective study assessed trough levels at the end of induction, which was 10–12 weeks after induction, and not at 4 weeks' induction as in the current study.…”

Best Practice for Therapeutic Drug Monitoring of Infliximab: Position Statement from the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

“…48,49 Table 1 provides an overview of infliximab target concentrations identified from prospective studies and post hoc analysis of RCTs during both induction and maintenance therapy. 10,13,[86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102] Post hoc analysis of the pivotal ACCENT I and ACCENT II trials in CD showed that infliximab trough concentrations $3.5 and $7.2 mg/L at week 14 were predictive of clinical response at week 54 and combined fistula response and CRP normalization (composite remission) at week 14, respectively. 10,86 Also, infliximab trough concentrations $20.2 mg/L at week 2 and $15 mg/L at week 6 were associated with composite complete remission at week 14.…”

Recent Advances in the Optimization of Anti-TNF Treatment in Patients with Inflammatory Bowel Disease

“…This was confirmed by the pediatric PAILOT (pediatric Crohn’s disease adalimumab level-based optimization treatment) study regarding ADA in CD and 1-year steroid-free clinical remission, as well as more composite outcomes (steroid-free clinical remission + normal CRP + normal FC (fecal calprotectin)) [ 76 ], and became further validated when applied for a longer time period, far from one year. Indicatively, in a 3-year Spanish prospective trial during a median follow-up at 84 [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , …”