Hepatic impairment leaves ivarmacitinib exposure largely unchanged, study finds
A 24-subject pharmacokinetic study found mild hepatic impairment had little effect on the JAK1 inhibitor's exposure, with a modest Cmax drop in moderate impairment.
Executive Summary
- A pharmacokinetic study in Chinese subjects compared how a JAK1 inhibitor is absorbed and cleared in people with normal liver function versus mild or moderate hepatic impairment.
- Liver impairment had little effect on overall drug exposure, with only a modest reduction in peak concentration in the moderate-impairment group.
- The result supports using the same dose in patients with mild or moderate hepatic impairment, without a dedicated dose-reduction step for this population.
- The single dose was tolerated across all groups, with adverse events occurring in about a third of subjects and no serious events reported.
The question
Drugs cleared partly through the liver can build up to higher, potentially unsafe levels in patients whose liver function is impaired, or can behave unpredictably if impairment changes how a drug's active metabolites form. Before a JAK1 inhibitor like ivarmacitinib can be dosed with confidence in patients who have coexisting liver disease, a common reality in the autoimmune and inflammatory populations the drug is being developed for, its sponsor needs to know whether hepatic impairment measurably changes how much drug reaches, and stays in, the bloodstream. PharmacokineticsPharmacokinetics and safety of SHR0302, a selective JAK1 inhibitor, in Chinese patients with hepatic impairment.Jul 17, 2026
How it was done
The open-label, parallel-group study enrolled 24 Chinese subjects in three groups of eight: normal hepatic function, mild hepatic impairment, and moderate hepatic impairment, graded by Child-Pugh classification. Each subject received a single 8 mg oral dose of ivarmacitinib. The primary endpoints were the area under the plasma concentration-time curve from dosing to 72 hours and extrapolated to infinity, plus peak plasma concentration (Cmax), each compared across the three groups; adverse events were tracked as a secondary measure. The trial ran in China, started in May 2020, and reached its primary completion in December 2020. NCT04293029Pharmacokinetics and Safety of SHR0302 in Patients With Hepatic ImpairmentNCT04293029
The result
Mild hepatic impairment had minimal effect on ivarmacitinib exposure compared with normal liver function. In the moderate-impairment group, Cmax was about 17% lower than in subjects with normal liver function, while total exposure, measured by AUC from dosing to the last measurable concentration and extrapolated to infinity, remained largely unchanged. Exposure to the drug's metabolite, SHR161279, fell by about 21% to 38% in both impairment groups, a larger shift than seen for the parent drug itself. PharmacokineticsPharmacokinetics and safety of SHR0302, a selective JAK1 inhibitor, in Chinese patients with hepatic impairment.Jul 17, 2026
Safety and tolerability
Eight of the 24 subjects, about a third, experienced treatment-emergent adverse events after the single dose, and no serious adverse events occurred in any group. The authors concluded that, based on this single-dose pharmacokinetic and safety profile, dose adjustment of ivarmacitinib may not be necessary in patients with mild or moderate hepatic impairment. PharmacokineticsPharmacokinetics and safety of SHR0302, a selective JAK1 inhibitor, in Chinese patients with hepatic impairment.Jul 17, 2026
Where this sits
Hepatic-impairment pharmacokinetic studies are a standard, required step for oral small molecules working through hepatic clearance pathways, and several other JAK1 inhibitors, including upadacitinib, abrocitinib, and ruxolitinib, have gone through comparable dose-finding work in special populations as part of their own development programs. The study here follows that established pattern for JAK1 inhibitors rather than testing a new hypothesis about the target.
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