Modeling the Efficacy of Natalizumab in Multiple Sclerosis Patients Who Switch From Every‐4‐Week Dosing to Extended‐Interval Dosing
| Autor: | Pei-Ran Ho, Ih Chang, Kumar Kandadi Muralidharan, Nolan Campbell |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
medicine.medical_specialty Multiple Sclerosis Population 030226 pharmacology & pharmacy progressive multifocal leukoencephalopathy Models Biological Drug Administration Schedule 03 medical and health sciences 0302 clinical medicine Natalizumab Pharmacokinetics Internal medicine Exposure‐Response medicine Humans Immunologic Factors Pharmacology (medical) Computer Simulation Dosing alpha‐4 integrin saturation extended interval dosing education Randomized Controlled Trials as Topic Pharmacology education.field_of_study business.industry Progressive multifocal leukoencephalopathy Multiple sclerosis Body Weight medicine.disease Discontinuation Treatment Outcome 030220 oncology & carcinogenesis Pharmacodynamics business medicine.drug |
| Zdroj: | Journal of Clinical Pharmacology |
| ISSN: | 1552-4604 0091-2700 |
| Popis: | Natalizumab is approved for multiple sclerosis treatment at a dose of 300 mg every 4 weeks. Extended‐interval dosing of natalizumab has been proposed as a strategy to mitigate the risk of progressive multifocal leukoencephalopathy, but the efficacy of extended‐interval dosing is not established. Previous models suggesting lower efficacy when initiating natalizumab treatment with extended‐interval dosing rather than every‐4‐week dosing are inconsistent with reports from clinical observations and real‐world studies conducted in patient populations switching to extended‐interval dosing after a period of receiving natalizumab every 4 weeks. Here, the efficacy of natalizumab extended‐interval dosing was modeled specifically in patients switching from every‐4‐week dosing to extended‐interval dosing. Published population pharmacokinetic/pharmacodynamic models were used to simulate the distribution of alpha‐4 integrin saturations for different body weight categories and dosing intervals (every 5, 6, 7, 8, 10, or 12 weeks). Generalized estimating equations relating alpha‐4 integrin saturation to probability of multiple sclerosis lesion or relapse were derived from RESTORE trial data, which included patients (n = 175) who discontinued natalizumab after being treated every 4 weeks for ≥1 year and had no relapses in the year before discontinuation. The model‐based simulations described indicate that every‐5‐week or every‐6‐week dosing is likely to maintain the efficacy of natalizumab, particularly at body weights |
| Databáze: | OpenAIRE |
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