Long-Term Follow-Up Results of Antiseizure Medication Withdrawal in Grade 2 and 3 Glioma Patients: A Prospective Observational Study

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the long-term results of seizure recurrence after antiseizure medication (ASM) withdrawal vs continuation in patients with diffuse glioma, grades 2 and 3.

METHODS: A prospective multicenter observational study was conducted, and patients were recruited from January 2014 until May 2016 from 3 neuro-oncology outpatient clinics in the Netherlands. The main inclusion criteria were as follows: history of ≥1 seizure, for which ASM was started; clinically and radiologically stable disease for ≥12 months; and seizure freedom for ≥12 months from the date of last antitumor treatment or seizure freedom for ≥24 months from the last seizure if seizures occurred after the last antitumor treatment. The primary outcome was time to recurrent seizure. A competing risk model was used to estimate cumulative incidences of recurrent seizure for ASM groups (i.e., ASM withdrawal vs ASM continuation) with death as the competing event. The proportional hazard assumption was violated for the ASM group; therefore, 2 Cox models were constructed for different time intervals (<48 months and ≥48 months since study inclusion).

RESULTS: A total of 71 patients were included (39 men [55%] and 58 older than 40 years [82%]); 46 patients with glioma (65%) were in the ASM withdrawal group and 25 (35%) in the ASM continuation group. The cumulative incidence of a recurrent seizure at 48 and 96 months was 48% (95% CI 33%-61%) and 66% (95% CI 48%-78%) for the ASM withdrawal group vs 28% (95% CI 12%-46%) and 52% (95% CI 31%-70%) for the ASM continuation group. The risk of a recurrent seizure differed in the 2 time intervals between the ASM continuation group (reference) and the ASM withdrawal group (cause-specific adjusted hazard ratio [aHR] 2.32 [95% CI 0.93-5.81], p = 0.071, during <48 months, and cause-specific aHR 0.73 [95% CI 0.21-2.49], p = 0.611, during ≥48 months since study inclusion).

DISCUSSION: Risk of recurrent seizure when withdrawing ASM was not statistically significantly higher in patients continuing ASM. However, a clinically relevant higher percentage of patients had a recurrent seizure in the ASM withdrawal group compared with the ASM continuation group. The lack of a statistical difference may be explained by the small sample size. Larger studies are needed to confirm these findings. Our results suggest that ASM withdrawal should be initiated cautiously and only when necessary.

CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that withdrawal of ASM does not significantly increase the risk of recurrent seizures in patients with glioma with stable disease and no seizures for >1 year. Confidence intervals do not exclude a clinically important increased risk of seizures.