Therapeutic Drug Monitoring During Induction of Anti-Tumor Necrosis Factor Therapy in Inflammatory Bowel Disease: Defining a Therapeutic Drug Window

Anti-tumor necrosis factor (TNF) therapy has revolutionized the treatment of inflammatory bowel disease (IBD). However, up to 30% of patients with IBD show no clinical benefit and are defined as having a primary nonresponse. Primary nonresponse to a biologic can be attributed to either pharmacokinetic or pharmacodynamic issues, such as those involved in secondary loss of response. Pharmacokinetic issues are linked to undetectable or subtherapeutic drug concentrations because of either an accelerated non-immune-mediated clearance or immunogenicity and the development of antidrug antibodies, whereas pharmacodynamic issues are likely related to "non-TNF driven" disease. Therapeutic drug monitoring (TDM), defined as the evaluation of drug concentrations and antidrug antibodies, has been proven effective for optimizing anti-TNF therapy in IBD. Nevertheless, most of the data for TDM relate to patients losing response during maintenance therapy, whereas much less is known about the therapeutic drug window and use of TDM during anti-TNF induction therapy. Recent exposure-response relationship studies, though, demonstrate that high serum anti-TNF drug concentrations during and early after induction therapy are associated with favorable therapeutic outcomes in IBD. This suggests that early optimization of anti-TNF therapy may prevent some of the primary nonresponse related to pharmacokinetic issues (low drug concentrations) and lead to better short- and long-term outcomes. This review will focus on the role of TDM during the induction phase of anti-TNF therapy.status: publishe

Efficacy and Safety Profile of Anti-tumor Necrosis Factor-α Versus Anti-integrin Agents for the Treatment of Crohn's Disease: A Network Meta-analysis of Indirect Comparisons

PURPOSE: To compare the benefits and harms of anti-tumor necrosis factor (TNF)-α and anti-integrin agents as induction and maintenance therapy in adult patients with Crohn's disease. METHODS: We searched MEDLINE and the Cochrane Central Register of Controlled Trials from inception through July 2015 for randomized clinical trials in patients with Crohn's disease who reported response or remission with anti-TNF-α or anti-integrin agents administered as induction and/or maintenance therapy. Data on the study population, interventions, outcome measures, adverse events, and study methods were extracted independently by 2 authors. FINDINGS: Among 2503 citations identified, 23 met the eligibility criteria. Random-effects model meta-analyses and network meta-analyses were performed. No statistically significant difference was observed between anti-TNF-α and anti-integrin agents with respect to induction and maintenance of response (odds ratio [OR] = 1.20 [95% CI, 0.73-1.96] from 14 trials and OR = 1.23 [95% CI, 0.50-3.03] from 8 trials, respectively) or remission (OR = 1.13 [95% CI, 0.72-1.76] from 17 trials and OR = 1.18 [95% CI, 0.55-2.50] from 9 trials, respectively). No difference was observed in the indirect comparison of trials that reported results on the subgroup of anti-TNF-α naive patients. The proportions of patients with adverse events, infections, and treatment discontinuations were similar between the agents. IMPLICATIONS: Our indirect treatment comparisons did not find a statistically significant difference between anti-TNF-α and anti-integrin agents for induction or maintenance therapy. In the absence of head-to-head comparisons, it remains unclear which patient is more likely to respond better to any of these agents.publisher: Elsevier articletitle: Efficacy and Safety Profile of Anti–tumor Necrosis Factor-α Versus Anti-integrin Agents for the Treatment of Crohn’s Disease: A Network Meta-analysis of Indirect Comparisons journaltitle: Clinical Therapeutics articlelink: http://dx.doi.org/10.1016/j.clinthera.2016.03.018 content_type: article copyright: © 2016 Elsevier Inc. All rights reserved.status: publishe