Model-based assessment of the benefits and risks of recombinant tissue plasminogen activator treatment in acute ischaemic stroke.
Br J Clin Pharmacol
; 84(11): 2586-2599, 2018 11.
Article
en En
| MEDLINE
| ID: mdl-30003573
ABSTRACT
AIMS:
Recombinant tissue plasminogen activator (rt-PA) is the only first-line agent approved by the US Food and Drug Administration to treat acute ischaemic stroke. However, it often causes the serious adverse event (AE) of haemorrhagic transformation. The present study developed a pharmacometric model for the rt-PA treatment effect and AE and, using the developed model, proposed a benefit-to-risk ratio assessment scheme as a supportive tool to optimize treatment outcome.METHODS:
The data from 336 acute ischaemic stroke patients were used. The treatment effect was assessed based on an improvement in National Institutes of Health Stroke Scale (NIHSS) scores, which were described using an item response theory (IRT)-based disease progression model. Treatment failure and AE probabilities, and their occurrence times, were described by incidence and time-to-event models. Using the developed model, benefit-to-risk ratios were simulated under various scenarios using the global benefit-to-risk trade-off ratio (GBR).RESULTS:
High initial NIHSS score and middle cerebral artery (MCA) stroke were risk factors for treatment failure, where the failure rate with MCA stroke was 2.87-fold higher than with non-MCA stroke. The haemorrhagic transformation time was associated with longitudinal changes in NIHSS scores. The benefit-to-risk ratio simulated was highest in minor stroke severity, with GBR >1 in all scenarios, and the ratio with non-MCA stroke was 2-3 fold higher than with MCA stroke.CONCLUSIONS:
The study demonstrated the feasibility of applying an IRT model to describing the time course of the rt-PA treatment effect and AE. Benefit-to-risk ratio analyses showed that the treatment was optimal in non-MCA stroke with minor stroke severity.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Isquemia Encefálica
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Activador de Tejido Plasminógeno
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Accidente Cerebrovascular
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Modelos Biológicos
Tipo de estudio:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
Br J Clin Pharmacol
Año:
2018
Tipo del documento:
Article