Trial reportNeurology2021
Safety and Efficacy of Natalizumab as Adjunctive Therapy for People With Drug-Resistant Epilepsy: A Phase 2 Study.
Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph
Trial report in Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03283371 (A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Exploring the Efficacy, Safety, and Tolerability of Natalizumab), which is not on this map. Cited by 14 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 4 pooled it
2.7field-weighted citation impact, top 9% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Exploring the Efficacy, Safety, and Tolerability of Natalizumab (BG00002) as Adjunctive Therapy in Adult Subjects With Drug-Resistant Focal Epilepsy
Who cites it
14 citing papers in PubMed, 4 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- Effectiveness and safety of single anti-seizure medication as adjunctive therapy for drug-resistant focal epilepsy based on network meta-analysis.Frontiers in pharmacology · 2025Pooled it
- A Systematic Review of the Predictive and Diagnostic Uses of Neuroinflammation Biomarkers for Epileptogenesis.International journal of molecular sciences · 2024Pooled it
- Immunomodulatory interventions for focal epilepsy.The Cochrane database of systematic reviews · 2023Pooled it
- Targeting Inflammatory Mediators in Epilepsy: A Systematic Review of Its Molecular Basis and Clinical Applications.Frontiers in neurology · 2022Pooled it
- Mechanisms and therapeutic advances of gut metabolites in the regulation of neuroimmune inflammatory diseases.Frontiers in immunology · 2026Review
- Beyond the gut: decoding the gut-immune-brain axis in health and disease.Cellular & molecular immunology · 2025Review
- Distinct T Cell Dysregulation Reflects Disease Severity and Progression in Infantile Epileptic Spasms Syndrome and Lennox-Gastaut Syndrome.Immune network · 2025Article
- Article
- Quantifying and controlling the impact of regression to the mean on randomized controlled trials in epilepsy.Epilepsia · 2023Article
- Systemic inflammation as a biomarker of seizure propensity and a target for treatment to reduce seizure propensity.Epilepsia open · 2023Review
- The neurovasculature as a target in temporal lobe epilepsy.Brain pathology (Zurich, Switzerland) · 2023Review
- Neuroinflammation and status epilepticus: a narrative review unraveling a complex interplay.Frontiers in pediatrics · 2023Review
- Immune Mechanism of Epileptogenesis and Related Therapeutic Strategies.Biomedicines · 2022Review
- A Postictal Traffic Jam.Epilepsy currentsArticle
Corrections and comments
- Commented on by
Authors and funding
18 authors at 1 institution in 1 country.
Jacqueline A FrenchFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
Andrew J ColeFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
Edward FaughtFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
William H TheodoreFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
Annamaria VezzaniFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
Kore LiowFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
Jonathan J HalfordFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.ORCID 0000-0003-1681-6744
Robert ArmstrongFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
Jerzy P SzaflarskiFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
Sarah HubbardFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
Jagdish PatelFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
Kun ChenFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
Wei FengFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
Marco RizzoFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study. marco.rizzo@biogen.com.
Jacob ElkinsFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
Gabrielle KnaflerFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
Kimberly A ParkersonFrom the NYU Grossman School of Medicine (J.A.F.), New York, NY; Massachusetts General Hospital (A.J.C.), Boston; Emory University School of Medicine (E.F.), Atlanta, GA; National Institutes of Health (W.H.T.), Bethesda, MD; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (A.V.), Milan, Italy; Hawaii Pacific Neuroscience (K.L.), Honolulu; Medical University of South Carolina (J.J.H.), Charleston; Asheville Neurology Specialists (R.A.), NC; University of Alabama at Birmingham (J.P.S.); Biogen (S.H., J.P., W.F., M.R.), Cambridge; Alexion (K.C.), Boston; Sarepta (J.E.), Cambridge; Envision Pharma Group (G.K.), Fairfield, CT; and Stoke Therapeutics (K.A.P.), Bedford, MA. K.C., J.E., and K.A.P. were affiliated with Biogen, Cambridge, MA, at the time of the study.
OPUS Study Group
Mario Negri Institute for Pharmacological Research · IT
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesTo explore efficacy/safety of natalizumab, a humanized monoclonal anti-α4-integrin antibody, as adjunctive therapy in adults with drug-resistant focal epilepsy.
methodsParticipants 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.
resultsOf 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%; 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.
Indexed as
AnticonvulsantsDrug Resistant EpilepsyAdultHumansNatalizumabSeizuresTreatment OutcomeAnticonvulsantsNatalizumab
Identifiers
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Registered trials
NCT03283371ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.