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Abstract
Background and Objectives To explore efficacy/safety of natalizumab, a humanized monoclonal anti–α4-integrin antibody, as adjunctive therapy in adults with drug-resistant focal epilepsy.
Methods Participants with ≥6 seizures during the 6-week baseline period were randomized 1:1 to receive natalizumab 300 mg IV or placebo every 4 weeks for 24 weeks. Primary efficacy outcome was change from baseline in log-transformed seizure frequency, with a predefined threshold for therapeutic success of 31% relative reduction in seizure frequency over the placebo group. Countable seizure types were focal aware with motor signs, focal impaired awareness, and focal to bilateral tonic-clonic. Secondary efficacy endpoints/safety were also assessed.
Results Of 32 and 34 participants dosed in the natalizumab 300 mg and placebo groups, 30 (94%) and 31 (91%) completed the placebo-controlled treatment period, respectively (one participant was randomized to receive natalizumab but not dosed due to IV complications). Estimated relative change in seizure frequency of natalizumab over placebo was −14.4% (95% confidence interval [CI] –46.1%–36.1%; p = 0.51). The proportion of participants with ≥50% reduction from baseline in seizure frequency was 31.3% for natalizumab and 17.6% for placebo (odds ratio 2.09, 95% CI 0.64–6.85; p = 0.22). Adverse events were reported in 24 (75%) and 22 (65%) participants receiving natalizumab vs placebo.
Discussion Although the threshold to demonstrate efficacy was not met, there were no unexpected safety findings and further exploration of possible anti-inflammatory therapies for drug-resistant epilepsy is warranted.
Trial Registration Information The ClinicalTrials.gov registration number is NCT03283371.
Classification of Evidence This study provides Class I evidence that IV natalizumab every 4 weeks, compared to placebo, did not significantly change seizure frequency in adults with drug-resistant epilepsy. The study lacked the precision to exclude an important effect of natalizumab.
Glossary
- AE=
- adverse event;
- ASD=
- antiseizure drug;
- BBB=
- blood–brain barrier;
- C-SSRS=
- Columbia Suicide Severity Rating Scale;
- CI=
- confidence interval;
- JCV=
- John Cunningham virus;
- PML=
- progressive multifocal leukoencephalopathy;
- VCAM-1=
- vascular cell adhesion molecule-1
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
OPUS Study Group coinvestigators are listed in the appendix at the end of the article.
Editorial, page 845
Class of Evidence: NPub.org/coe
- Received January 21, 2021.
- Accepted in final form August 27, 2021.
- © 2021 American Academy of Neurology
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