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Review
. 2023 Nov 16;12(22):7132.
doi: 10.3390/jcm12227132.

Drug Clearance in Patients with Inflammatory Bowel Disease Treated with Biologics

Tina Deyhim  1 , Adam S Cheifetz  1 , Konstantinos Papamichael  1
Affiliations
Review

Drug Clearance in Patients with Inflammatory Bowel Disease Treated with Biologics

Tina Deyhim et al. J Clin Med. .

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.

Keywords: anti-TNF therapy; clearance; inflammatory bowel disease; mirikizumab; model informed precision dosing; pharmacokinetic dashboard; risankizumab; therapeutic drug monitoring; ustekinumab; vedolizumab.

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Conflict of interest statement

K.P. received lecture/speaker fees from Physicians Education Resource LLC and Grifols; scientific advisory board fees from ProciseDx Inc and Scipher Medicine Corporation; and serves as a consultant for Prometheus Laboratories Inc. A.S.C. served as a consultant and/or advisory board member for Janssen, Abbvie, Protagonist, Spherix, Artizan, Food is Good, Clario, Pfizer, Fresenius Kabi, Artugen, ProciseDx, Prometheus, Equillium, Samsung, Arena, Bacainn, Bristol Myers Squibb, Takeda; unbranded speaker for BMS and Abbvie. T.D declares no conflicts of interest.

Figures

Figure 1
Figure 1
Variables associated with higher clearance of biologics in patients with inflammatory bowel disease. CD: Crohn’s disease; IBD: inflammatory bowel disease; UC: ulcerative colitis; ADA; anti-drug antibodies; CRP: C-reactive protein, AZA: azathioprine, MTX: methotrexate, FC: fecal calprotectin, CDAI: Crohn’s disease activity index, PMS: partial Mayo score, WBC: white blood count, ESR: erythrocyte sedimentation rate, EOW: every other week, PCDAI: pediatric CDAI, ALP: alkaline phosphatase; nCD64: neutrophil CD64; ↑ higher; ↓ lower.
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