Neurological
Natalizumab has been poorly effective in patients with drug-resistant epilepsy
Concomitant treatment with natalizumab did not change seizure frequency in a small sample of patients with severely drug-resistant focal epilepsy, but no unexpected safety findings were reported according to a phase 2 study results published in Neurology.
Surgery, neurostimulation, special diets and / or other therapies can be used in patients who have not been able to achieve lasting freedom from seizures after appropriate attempts with 2 anti-epileptic drugs. The current study aimed to evaluate the safety and effectiveness of natalizumab as add-on therapy in adults with drug-resistant epilepsy.
The randomized, placebo-controlled, double-blind phase 2 (OPUS; ClinicalTrials.gov Identifier: NCT03283371) included patients from 31 US sites with drug-resistant focal epilepsy who had 6 or more seizures during the baseline period. The study consisted of a 6-week prospective baseline phase followed by a double-blind, placebo-controlled phase in which participants were randomized 1: 1 to receive natalizumab 300 mg intravenously or placebo every 4 weeks for 24 weeks.
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The change in the logarithmically transformed seizure frequency compared to the initial value was the primary efficacy endpoint with a predefined threshold value for therapeutic success of 31% relative reduction in seizure frequency compared to the participants in the placebo group. The incidence of adverse events and serious adverse events were determined to assess the safety of treatment.
The study sample included 30 patients in the natalizumab and 31 patients in the placebo group who completed the placebo-controlled treatment period.
The mean deviation from baseline in the logarithmically transformed seizure frequency from weeks 8 to 24 was -0.58 for natalizumab and -0.43 for placebo, which is a relative change from placebo of -14.4% (95% CI, -46, 1% to 36.1.) Corresponds to%; P = .51). The proportion of participants with a 50% or more reduction in seizure frequency over the same period was 31.3% for natalizumab and 17.6% for placebo (odds ratio 2.09; 95% CI 0.64–6, 85; P = 0.22).
No unexpected safety findings with adverse events were reported in 24 (75%) of the natalizumab-treated patients and 22 (65%) of the participants in the placebo group. Serious adverse events were reported in 1 participant (3%) in each group. In the natalizumab group, there was only 1 incidence (urticaria) of an adverse event that resulted in treatment discontinuation.
Limitations of the study included the small sample size and the higher proportion of patients with focal to bilateral tonic-clonic seizures observed during the baseline period in the placebo group, where the effects of natalizumab may have been reduced.
“Although the threshold of effectiveness was not reached, there were no unexpected safety findings, and pharmacodynamic evidence suggesting a consistent mechanism of action suggests that there are good reasons to continue exploring drugs that target inflammatory processes specific to the CNS are aimed to treat drug-resistant epilepsy. ”the researchers concluded.
Disclosure: This study was supported by Biogen Inc. For a full list of specifications, see the original reference.
relation
French JA, Cole AJ, Faught E, et al. Safety and efficacy of natalizumab as add-on therapy for people with drug-resistant epilepsy: a phase 2 study. Neurology. Published online November 2, 2021. doi: 10.1212 / WNL.0000000000012766