Drug Clearance in Patients with Inflammatory Bowel Disease Treated with Biologics

Abstract

Biological therapy is very effective for treating patients with moderate to severe inflammatory bowel disease (IBD). However, up to 40% can have primary non-response, and up to 50% of the patients can experience a loss of response to anti-tumor necrosis factor therapy. These undesirable outcomes can be attributed to either a mechanistic failure or pharmacokinetic (PK) issues characterized by an inadequate drug exposure and a high drug clearance. There are several factors associated with accelerated clearance of biologics including increased body weight, low serum albumin and immunogenicity. Drug clearance has gained a lot of attention recently as cumulative data suggest that there is an association between drug clearance and therapeutic outcomes in patients with IBD. Moreover, clearance is used by model informed precision dosing (MIDP) tools, or PK dashboards, to adjust the dosing for reaching a target drug concentration threshold towards a more personalized application of TDM. However, the role of drug clearance in clinical practice is yet to be determined. This comprehensive review aims to present data regarding the variables affecting the clearance of specific biologics, the association of clearance with therapeutic outcomes and the role of clearance monitoring and MIPD in patients with IBD.

High Body Mass Index and Response to Anti-Tumor Necrosis Factor Therapy in Pediatric Crohn’s Disease

“…Pharmacokinetic studies have demonstrated that obese patients have increased drug clearance of anti-TNF with shortened half-life and lower trough drug concentrations compared with normal-weight patients (15)(16)(17). In addition, it has been found that patients with higher visceral adiposity required higher IFX troughs (13.6-15.9) as compared with patients with lower visceral adiposity (3.9-4.9) to maintain steroid-free and endoscopic remission (18).…”

Role of Functionalized Peptides in Nanomedicine for Effective Cancer Therapy

“…However, since many cancer drugs are hydrophobic, injecting the appropriate drug concentration required for treatment is difficult, and direct drug injection often causes side effects owing to non-specific effects on cancer and normal cells [16][17][18][19]. Additionally, the injected drugs are removed by the reticuloendothelial system (RES), and only a small fraction of the drug is delivered to the cancer cells, making it difficult to reach a sufficient concentration for treatment [20][21][22][23][24]. Drug delivery systems have been developed over the past few years [25][26][27].…”