Population pharmacokinetics and exposure-response analyses for efficacy and safety of upadacitinib in patients with axial spondyloarthritis.
Clin Transl Sci
; 17(2): e13733, 2024 02.
Article
en En
| MEDLINE
| ID: mdl-38344875
ABSTRACT
Upadacitinib is an orally administered, selective, Janus kinase inhibitor that is approved for several auto-immune conditions, such as axial spondyloarthritis, an inflammatory rheumatic disease that includes ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). The approvals of upadacitinib for the treatment of AS and nr-axSpA were based on the safety and efficacy data for upadacitinib 15 mg once-daily compared to placebo from the SELECT-AXIS 1 and SELECT-AXIS 2 studies. Population pharmacokinetic analyses based on data from 244 patients with axSpA showed that the pharmacokinetics of upadacitinib were comparable in subjects with AS and nr-axSpA. Exposure-response relationships were characterized for key efficacy and safety end points using data from 482 patients with axSpA. The exposure-response analyses for efficacy based on Assessment of SpondyloArthritis International Society (ASAS)20 and ASAS40 responses at week 14, showed a clear differentiation from placebo with no evidence of increased responses with increasing upadacitinib plasma exposures. There were no clear exposure-response trends observed for safety end points that included serious infections, herpes zoster, pneumonia, lymphopenia (grade ≥3), neutropenia (grade ≥3), or a greater than 2 g/dL decrease in hemoglobin from baseline through week 14. The exposure-response analyses for efficacy and safety presented here supported the favorable benefit-risk profile with the use of upadacitinib 15 mg once-daily for the treatment of axSpA.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Espondilitis Anquilosante
/
Antirreumáticos
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Espondiloartritis
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Espondiloartritis Axial no Radiográfica
Tipo de estudio:
Clinical_trials
Límite:
Humans
Idioma:
En
Revista:
Clin Transl Sci
/
Clinical and translational science (Online)
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos