Proactive Monitoring of Adalimumab Trough Concentration Associated With Increased Clinical Remission in Children With Crohn’s Disease Compared With Reactive Monitoring

Rottlerin ameliorates DSS-induced colitis by improving intestinal barrier function via activation of the Epac-2/Rap-1 signaling pathway

“…The abnormal expression of TJ proteins in the epithelial cell monolayer may disrupt the structure and function of TJs, thereby destroying the completeness of barrier [10] . Inflammation is considered to be the basic mechanism of the pathophysiology of intestinal damage [11] . Relative increases in the levels of inflammatory factors (TNF-α, IL-17A…”

Is It Prime Time for Proactive Therapeutic Drug Monitoring of Anti-Tumor Necrosis Factor Therapy in Inflammatory Bowel Disease?

“…The Trough Level Adapted Infliximab Treatment (TAXIT) RCT, although it missed its primary end point owing to some methodologic issues (optimization of all patients prior to randomization, only 1 year of follow-up, delayed optimization until next dose, and a rather low therapeutic drug window [3-7 mg/mL] to target) showed that even a 1-time dose optimization increased clinical and biochemical remission rates in CD and met several secondary outcomes favoring ongoing proactive TDM during the maintenance phase (Table 1). 5 The Drugconcentration versus Symptom-driven Dose Adaptation of Infliximab in patients with active Crohn's disease (TAILORIX) RCT, 6 owing to several methodologic and design issues extensively described previously and in the current article by Assa et al 12 unfortunately did not shed more light on the role of proactive TDM. However, a recent post hoc analysis of TAILORIX did show that higher infliximab concentrations during induction therapy at week 2 (>23.1 mg/mL) and week 6 (>10 mg/mL) were associated with early endoscopic remission at week 12.…”

“…Furthermore, there is an increasing body of literature to support the benefit of proactive over empiric dose escalation and/or reactive TDM, although most of these studies are retrospective (Table 1). [5][6][7][8][9][10][11][12][13] In the current issue of Gastroenterology, Assa et al 12 provide increasing supportive evidence for the usefulness of proactive TDM over standard dosing and reactive TDM in their randomized controlled trial (RCT) called Paediatric Crohn's disease Adalimumab-Level-based Optimisation Treatment (PAILOT). This well-designed pragmatic study prospectively assessed whether proactive TDM was superior to reactive testing in pediatric Crohn's disease (CD).…”

“…The primary end point, sustained corticosteroid-free clinical remission (defined as a Pediatric Crohn's Disease Activity Index of <10 at all visits), was significantly higher in the proactive group compared with the reactive TDM group (31 [82%] vs 19 [48%]; P ¼ .002). 12 Furthermore, several secondary outcomes also favored proactive over reactive TDM, including the composite outcome of sustained corticosteroid-free remission, C-reactive protein of 0.5 mg/dL, Pediatric Crohn's Disease Activity Index of <10, and fecal calprotectin of 150 mg/g (16 [42%] vs 5 [12%]; P ¼ .003). 12 The benefits of proactive TDM in this study were seen despite the rather low targeted therapeutic adalimumab trough concentration of 5 mg/mL and the fact that only the proactive group underwent deescalation if adalimumab trough concentrations were >10 mg/mL.…”

“…12 Furthermore, several secondary outcomes also favored proactive over reactive TDM, including the composite outcome of sustained corticosteroid-free remission, C-reactive protein of 0.5 mg/dL, Pediatric Crohn's Disease Activity Index of <10, and fecal calprotectin of 150 mg/g (16 [42%] vs 5 [12%]; P ¼ .003). 12 The benefits of proactive TDM in this study were seen despite the rather low targeted therapeutic adalimumab trough concentration of 5 mg/mL and the fact that only the proactive group underwent deescalation if adalimumab trough concentrations were >10 mg/mL. The study actually showed that a 10.0 mg/mL threshold performed better than 7.5 and 5.0 mg/mL with respect to Pediatric Crohn's Disease Activity Index and C-reactive protein levels.…”