Pharmacokinetics of IL-23p19 Inhibitors: A Systematic Review Across Immune-Mediated Inflammatory Diseases

Abstract

Interleukin (IL)-23p19 inhibitors are increasingly used in immune-mediated inflammatory diseases (IMIDs), particularly inflammatory bowel disease (IBD). Almost half of patients show inadequate response, partly due to pharmacokinetic (PK) variability. However, a comprehensive overview of their PK parameters is lacking, which limits understanding of population variability. This systematic review assessed the PK of IL-23p19 inhibitors in healthy subjects, IBD and other IMIDs. A systematic literature search was performed in PubMed/MEDLINE and Embase. Studies were screened by two independent researchers. Quality was assessed using the Cochrane risk of bias tool and the Clinical Pharmacokinetic Study Checklist. A total of 21 studies were included (risankizumab n = 9, guselkumab n = 6, tildrakizumab n = 3, mirikizumab n = 3), covering healthy subjects, psoriasis, psoriatic arthritis, Crohn’s disease (CD), ulcerative colitis (UC) and pustular/erythrodermic psoriasis. Only one study examined a distinct IBD group, specifically, mirikizumab in pediatric UC. For risankizumab, dose-normalized maximum concentrations and area under the concentration‑time curves over a dosing interval, along with central and peripheral volume of distribution and clearance were generally similar across CD and UC. Patients with CD and UC demonstrated increased risankizumab trough levels over consecutive dosing intervals, while an opposite trend was observed for other IMIDs. Covariate analysis revealed that only albumin in UC and body weight in CD were relevant covariates to risankizumab PK. Limited PK data and lack of subphenotype-specific data on IBD highlight the need for future studies to better define PK parameters. Also, more research is needed to guide personalized dosing strategies for IL-23p19 inhibitor use in IBD, as well as in other IMIDs. Doctors can prescribe biologics to patients diagnosed with autoimmune disease. Not all patients respond to biologic therapy in the same way. In part, this is caused by their bodies processing the biologics differently. Therefore, it is important to study how biologics are processed by the human body. A new class of biologics, called IL-23p19 inhibitors, have already shown promising treatment results for patients with psoriasis and those with inflammatory bowel disease (IBD). Unfortunately, differences in treatment responses among patients are observed, making it difficult for doctors to know whether the treatment would be successful for their patients. In order to provide doctors with more insights in this topic, this study summarized all the current knowledge on ways in which IL-23p19 inhibitors are processed by the bodies of patients with autoimmune disorders, with a specific focus on patients with IBD. Our findings show that only limited research has been done for patients with IBD. Even less attention has been given to specific IBD subtypes. For example, research is scarce with regard to patients with Crohn’s disease who experience frequent perianal disease activity and fistulas. We also highlight the importance of personalized treatment and show how our study can help guide it. Understanding how IL-23p19 inhibitors are processed by the body can help doctors choose the best dose and time for each patient. This leads to treatments that are better tailored to the needs of specific patients, resulting in better treatment outcomes and increased quality of life for patients living with autoimmune diseases.