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Ustekinumab dosing individualization in Crohn's disease guided by a population pharmacokinetic-pharmacodynamic model [Elektronski vir]Zdovc, Jurij, farmacija ...Ustekinumab is a monoclonal antibody used in Crohn's disease (CD). Dose optimization in case of non-response and the role of pharmacokinetic-pharmacodynamic (PK-PD) monitoring remain unresolved ... dilemmas in clinical practice. We aimed to develop a population PK-PD model for ustekinumab in CD and simulate efficacy of alternative dosing regimens. We included 57 patients and recorded their characteristics during 32 weeks after starting with ustekinumab therapy. Serum ustekinumab concentration was prospectively measured and fecal calprotectin (FC) concentration was used to monitor the disease activity. Ustekinumab PK-PD was described by a two-compartment target-mediated drug disposition model linked to an indirect response model. Lower fat-free mass, higher serum albumin, previous non-exposure to biologics, FCGR3A-158 V/V variant and lower C-reactive protein were associated with higher ustekinumab exposure. Model-based simulation suggested that 41.9% of patients receiving standard dosing achieve biochemical remission at week 32. In patients not achieving remission with standard dosing at week 16, transition to 4-weekly subcutaneous maintenance dosing with or without intravenous reinduction resulted in comparably higher remission rates at week 32 (51.1% vs. 49.2%, respectively). Our findings could be used to guide stratified ustekinumab treatment in CD, particularly in patients with unfavorable characteristics, who might benefit from early transition to 4-weekly maintenance dosing.Source: Pharmaceutics [Elektronski vir]. - ISSN 1999-4923 (Vol. 13, iss. 10, 2021, str. 1-16)Type of material - e-article ; adult, seriousPublish date - 2021Language - englishCOBISS.SI-ID - 78625027
Author
Zdovc, Jurij, farmacija |
Hanžel, Jurij |
Kurent, Tina, dr. med. |
Sever, Nejc, dr. med. |
Koželj, Matic, dr. med. |
Smrekar, Nataša, 1967- |
Novak, Gregor, medicina, 1984- |
Štabuc, Borut |
Vovk, Tomaž, 1972- |
Ostanek, Barbara, 1972- |
Drobne, David, 1978- |
Grabnar, Iztok
Topics
Crohnova bolezen |
Tarčna zdravila |
vnetje črevesja |
terapevtsko spremljanje zdravil |
fekalni kalprotektin |
ustekinumab |
inflammatory bowel disease |
fecal calprotectin |
pharmacokinetics-pharmacodynamics |
therapeutic drug monitoring
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Zdovc, Jurij, farmacija | 51148 |
Hanžel, Jurij | 54194 |
Kurent, Tina, dr. med. | |
Sever, Nejc, dr. med. | |
Koželj, Matic, dr. med. | 38330 |
Smrekar, Nataša, 1967- | 17902 |
Novak, Gregor, medicina, 1984- | 38328 |
Štabuc, Borut | 11949 |
Vovk, Tomaž, 1972- | 18155 |
Ostanek, Barbara, 1972- | 18154 |
Drobne, David, 1978- | 38327 |
Grabnar, Iztok | 16107 |
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