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Published on: October 27, 2014
Effectiveness of Antiseizure Medication Duotherapies in Patients With Glioma: A Multicenter Observational Cohort
Pim B van der Meer1, Linda Dirven2, Marta Fiocco2
1From the Department of Neurology (P.M., L.D., M.J.B.T., J.A.F.K.), Leiden University Medical Center; Department of Neurology (L.D., M.J.V., M.J.B.T., J.A.F.K.), Haaglanden Medical Center, The Hague; Department of Biomedical Data Sciences (M.F.), Medical Statistics, Leiden University Medical Center; Mathematical Institute (M.F.), Leiden University; Department of Neurology (M.C.M.K.), Amsterdam University Medical Centers, location VUmc; and Brain Tumor Center at Erasmus Medical Center Cancer Institute (M.J.B.), Rotterdam, the Netherlands. pbvandermeer@lumc.nl.
Background And Objectives:
About 30% of patients with glioma need an add-on antiseizure medication (ASM) due to uncontrolled seizures on ASM monotherapy. This study aimed to determine whether levetiracetam combined with valproic acid (LEV + VPA), a commonly prescribed duotherapy, is more effective than other duotherapy combinations including either LEV or VPA in patients with glioma.
Methods:
In this multicenter retrospective observational cohort study, treatment failure (i.e., replacement by, addition of, or withdrawal of an ASM) for any reason was the primary outcome. Secondary outcomes included (1) treatment failure due to uncontrolled seizures and (2) treatment failure due to adverse effects. Time to treatment failure was estimated from the moment of ASM duotherapy initiation. Multivariable cause-specific Cox proportional hazard models were estimated to study the association between risk factors and treatment failure. The maximum duration of follow-up was 36 months.
Results:
A total of 1,435 patients were treated with first-line monotherapy LEV or VPA, of which 355 patients received ASM duotherapy after they had treatment failure due to uncontrolled seizures on monotherapy. LEV + VPA was prescribed in 66% (236/355) and other ASM duotherapy combinations including LEV or VPA in 34% (119/355) of patients. Patients using other duotherapy vs LEV + VPA had a higher risk of treatment failure for any reason (cause-specific adjusted hazard ratio [aHR] 1.50 [95% CI 1.07-2.12], p = 0.020), due to uncontrolled seizures (cause-specific aHR 1.73 [95% CI 1.10-2.73], p = 0.018), but not due to adverse effects (cause-specific aHR 0.88 [95% CI 0.47-1.67], p = 0.703).
Discussion:
This observational cohort study suggests that LEV + VPA has better efficacy than other ASM combinations. Similar toxicities were experienced in the 2 groups.
Classification Of Evidence:
This study provides Class III evidence that for patients with glioma with uncontrolled seizures on ASM monotherapy, LEV + VPA has better efficacy than other ASM combinations.
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