AUTHOR=Zhu Kouzhu , Ding Xiaoliang , Xue Ling , Liu Linsheng , Wang Yan , Li Yun , Xi Qinhua , Pang Xueqin , Chen Weichang , Miao Liyan TITLE=Optimising infliximab induction dosing to achieve clinical remission in Chinese patients with Crohn’s disease JOURNAL=Frontiers in Pharmacology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1430120 DOI=10.3389/fphar.2024.1430120 ISSN=1663-9812 ABSTRACT=Aims

A strategy based on therapeutic drug monitoring and population pharmacokinetic (popPK) models would likely increase the rate of clinical remission (CR) after infliximab (IFX) induction in patients with Crohn’s disease (CD). This study aimed to evaluate the relationship between early IFX levels and antibodies to infliximab (ATI) and CR at week 14 and simulate the probability of attaining the identified exposure target.

Methods

Patients with CD (n = 140) treated with IFX were enrolled to develop the popPK model. Of these, 43 moderate-to-severe patients with CD were followed up at week 14. Simulations were performed on patients with different dosage regimens and covariates.

Results

IFX levels >20.08 μg/mL at week 2, >18.44 μg/mL at week 6, and >3.08 μg/mL at week 14 were linked to CR. A one-compartment model fit the data best. The covariates influencing clearance were fat free mass, albumin and ATI levels. To achieve IFX levels >20.08 μg/mL at week 2, ≥400 mg IFX was predicted to be required in over 50% patients with 45–70 kg and 35–45 g/L albumin, except for patients with 70 kg and 30 g/L albumin.

Conclusion

IFX levels >20.08 μg/mL at week 2 and absence of ATI at week 14 are associated with CR. Optimising IFX induction dosing will be critical to achieve the target of early IFX levels associated with CR.