Population pharmacokinetic‐pharmacodynamic modelling of platelet time‐courses following administration of abrocitinib

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.