Population pharmacokinetic-pharmacodynamic modelling of platelet time-courses following administration of abrocitinib (Open Access)

We published the Platelet modeling for abrocitinib, primarily work performed by Jessica Wojciechowski, in the British Journal of Clinical Pharmacology.

Link to Manuscript: https://doi.org/10.1111/bcp.15334

Citation: Wojciechowski J, Malhotra BK,Wang X, Fostvedt L, Valdez H, Nicholas T. Population pharmacokinetic-pharmacodynamic modelling of platelet time-courses following administration of abrocitinib. Br J ClinPharmacol. 2022;88(8):3856‐3871. doi:10.1111/bcp.15334WOJCIECHOWSKIET AL.3869

Abrocitinib is a selective Janus kinase 1 inhibitor for the treatment of moderate-to-severe atopic dermatitis. Herein we describe the time-course of drug-induced platelet reduction following abrocitinib administration, identify covariates affecting platelet counts, and determine the probability of patients experiencing thrombocytopaenia while receiving abrocitinib.

This analysis included data from two Phase 2 and three Phase 3 studies in psoriasis and atopic dermatitis patient populations administered abrocitinib 10–400 mg QD orally for up to 12 weeks, with platelet counts determined up to week 16. A semi-mechanistic model was developed to assess the impact of baseline platelet counts (170, 220 and 270 × 1000/μL), age and race on the platelet nadir and week 12 counts with once-daily abrocitinib 200 mg or 100 mg.

Decreases in platelet counts were transient with the nadir occurring on average 24 days (95% prediction interval, 23–24) after continuous administration of abrocitinib 200 mg QD. Following administration of once-daily abrocitinib 200 mg, the probabilities of thrombocytopaenia (<150 × 1000/μL) at the nadir were 8.6% and 95.5% for the typical patient with baseline platelet count of 270 × 1000/μL or 170 × 1000/μL, respectively. Adolescents had a lower probability of thrombocytopaenia compared with adults; platelet count distribution was similar in Asian and Western patients at the nadir and at week 12.

This analysis supports the safety of once-daily abrocitinib 200 mg and 100 mg dosing regimens, with low probability of thrombocytopaenia during treatment, except for higher risk of low-grade thrombocytopaenia that diminished after 4 weeks in patients with low baseline platelet counts.