Expected Spesolimab Plasma Exposure following Intravenous and Subcutaneous Dosing in Patients with Generalized Pustular Psoriasis

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Jason Hawkes
Jason Guercio
Sree Kurup
Xiujiang Li
Mark Lebwohl


PK, intravenous and subcutaneous dosing, spesolimab, Generalized Pustular Psoriosis


Introduction: Generalized pustular psoriasis (GPP) is a chronic, potentially life-threatening inflammatory skin disease characterized by widespread flares of sterile pustules. Spesolimab is a first-in-class anti-interleukin-36 receptor monoclonal antibody approved to treat GPP flares in adults via intravenous (IV) infusion. The aim of this study was to simulate the plasma pharmacokinetics (PK) of IV versus subcutaneous (SC) doses of spesolimab to compare drug exposure profiles and support dosing strategies in patients with GPP.

 Methods: A population PK model was developed using individual-level PK, anti-drug antibody, and covariate data from eighteen studies in which subjects were treated with IV or SC spesolimab.1 The resulting PK model was used to simulate concentration-time profiles following varying doses of IV and SC spesolimab. Peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), and area under the curve (AUC) were summarized for each dose regimen.

Results: Simulated spesolimab exposures demonstrated that the Cmax and AUC of the single dose 900 mg IV infusion consistently exceeded that of various single doses of SC spesolimab tested. A SC dose greater than two-fold higher would be required to attain a Cmax comparable to that of spesolimab 900 mg IV. The difference in exposure between the two administration routes was most pronounced in the first 2 weeks after administration. Slow absorption is expected with SC injection, with Tmax attained at later time points after SC dosing compared to immediately following the 90-minute infusion for IV dosing. Results were the same when simulating a two-dose regimen administered one week apart.

 Conclusions: PK simulations suggest that treatment with IV and SC spesolimab can result in differences in drug exposure in clinical practice. The immediate and high exposure of IV spesolimab compared with the lower exposure of SC spesolimab are supportive of IV dosing with spesolimab in acute GPP flare treatment vs SC dosing.


1. SPEVIGO® prescribing information. Available at:- https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761244s000lbl.pdf.

2. Boehringer Ingelheim. Data on File: Modeling and simulation report: population pharmacokinetics and exposure-response of spesolimab in Generalized Pustular Psoriasis. 2023;c41839684-01

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