Evidence map›Paper›PMID 40625668›Full record

ArticleNeurology open access2025

A Phase-2B Double-Blind Randomized International Prospective Trial of Inebilizumab in NMDAR Encephalitis: The ExTINGUISH Trial.

Ka-Ho Wong, Gregory Scott Day, James C Torner, Merit Cudkowicz, Christopher S Coffey, Hyun Joo Sophie Cho, Ursula Utz, David B Clifford, Eliezer Katz, John Ratchford and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology open access, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Autoimmune encephalitis.Nature reviews. Disease primers · 2025
    Review
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Ka-Ho WongDepartment of Neurology, University of Utah, Salt Lake City, UT.
Gregory Scott DayDepartment of Neurology, Mayo Clinic in Florida, Jacksonville, FL.
James C TornerNeuroNEXT Data Coordinating Center, Clinical Trials Statistical Data Management Center, Department of Biostatistics, University of Iowa, IA.
Merit CudkowiczDepartment of Neurology, NeuroNEXT Clinical Coordinating Center, Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Christopher S CoffeyNeuroNEXT Data Coordinating Center, Clinical Trials Statistical Data Management Center, Department of Biostatistics, University of Iowa, IA.
Hyun Joo Sophie ChoThe National Institute of Neurological Disorders and Stroke (NINDS), of the National Institutes of Health, Bethesda, MD.
Ursula UtzThe National Institute of Neurological Disorders and Stroke (NINDS), of the National Institutes of Health, Bethesda, MD.
David B CliffordDepartment of Neurology, Washington University, St. Louis, MO.
Eliezer KatzFormerly with Viela Bio at Time of Contributions; Viela Bio Was Subsequently Acquired By Horizon and Later Amgen, Thousand Oaks, CA.
John RatchfordFormerly with Viela Bio at Time of Contributions; Viela Bio Was Subsequently Acquired By Horizon and Later Amgen, Thousand Oaks, CA.
Susan FlavinAmgen, Thousand Oaks, CA.
Annalisa Dialino-FelixAmgen, Thousand Oaks, CA.
Lisa M DillAmgen, Thousand Oaks, CA.
Cornelia KampClinical Materials Services Unit (CMSU) in the Center for Human Experimental Therapeutics (CHET), University of Rochester, Rochester, NY.
Eric C KlawiterDepartment of Neurology, NeuroNEXT Clinical Coordinating Center, Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
John Robinson SingletonDepartment of Neurology, University of Utah, Salt Lake City, UT.
Janel FedlerNeuroNEXT Data Coordinating Center, Clinical Trials Statistical Data Management Center, Department of Biostatistics, University of Iowa, IA.
Elizabeth A KlingnerNeuroNEXT Data Coordinating Center, Clinical Trials Statistical Data Management Center, Department of Biostatistics, University of Iowa, IA.
Dixie EcklundNeuroNEXT Data Coordinating Center, Clinical Trials Statistical Data Management Center, Department of Biostatistics, University of Iowa, IA.
David KlementsDepartment of Neurology, NeuroNEXT Clinical Coordinating Center, Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Michele CostiganNeuroNEXT Data Coordinating Center, Clinical Trials Statistical Data Management Center, Department of Biostatistics, University of Iowa, IA.
Erin SteinhartDepartment of Neurology, NeuroNEXT Clinical Coordinating Center, Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Brenda PearsonNeuroNEXT Data Coordinating Center, Clinical Trials Statistical Data Management Center, Department of Biostatistics, University of Iowa, IA.
Christina DesirDepartment of Neurology, NeuroNEXT Clinical Coordinating Center, Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Josep O DalmauIDIBAPS-Hospital Clinic, University of Barcelona, Barcelona, Spain.
Maarten J TitulaerDepartment of Neurology, University Erasmus Medical Center, Rotterdam, the Netherlands.
Stacey L ClardyDepartment of Neurology, University of Utah, Salt Lake City, UT.

Funding

Clinical Coordinating Center Network of Excellence in Neuroscience Clinical TrialU01NS077179 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI Merit E CUDKOWICZ, Aleksandar Videnovic · 2011 to 2026
$43.4M
Network of Excellence in Neuroscience Clinical Trials (NEXT)-DCCU01NS077352 · NINDS · UNIVERSITY OF IOWA · PI CHRISTOPHER S. COFFEY · 2011 to 2026
$28.1M
A Phase-2b, Double-Blind, Randomized Controlled Trial to Evaluate the Activity and Safety of Inebilizumab in Anti-N-methyl-D-aspartate receptor (NMDAR) Encephalitis and Assess Markers of DiseaseU01NS120901 · NINDS · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Stacey Lynn Clardy · 2021 to 2026
$19.6M
NINDS NIH HHS U01 NS077179NINDS NIH HHS U01 NS077352NINDS NIH HHS U01 NS120901
6 · The paper itself

Abstract

Background and Objectives: The lack of approved therapies for N-methyl-d-aspartate receptor (NMDAR) encephalitis has contributed to substantial variability in treatment. Inebilizumab is a humanized anti-CD19 monoclonal antibody that can be administered intravenously. Inebilizumab may be an efficacious treatment for patients with NMDAR encephalitis, with the potential to achieve early robust and sustained suppression CD19 Methods: The ExTINGUISH trial is a multisite, phase 2B, randomized, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of inebilizumab 300 mg for the acute treatment of participants with moderate-to-severe NMDAR encephalitis. ExTINGUISH will randomize 116 patients across the United States and Europe. Participants will receive standard first-line immunotherapies (intravenous steroids and intravenous immunoglobulins and/or plasma exchange) before randomization (1:1). In addition, cyclophosphamide rescue therapy will be offered to participants with persistent moderate-to-severe disease 6 weeks after randomization. Primary outcomes will be measured 16 weeks from randomization using the change in the adapted ExTINGUISH modified Rankin scale and accepted safety measures in 32 weeks. Secondary outcomes will be measured up to 96 weeks and include comprehensive neuropsychological tests, bedside cognitive screening tools, and quality-of-life/functional indices. Clinical data will be combined with blood and CSF biomarkers of immune activation to inform putative biologic contributors to outcomes (exploratory outcomes). Study operations are supported by the National Institute of Neurological Disorders and Stroke-supported Network for Excellence in Neuroscience Clinical Trial (NeuroNEXT) infrastructure. Discussion: The ExTINGUISH trial will determine the safety and efficacy of inebilizumab as a treatment of NMDAR encephalitis while evaluating the utility of clinical, cognitive, and quality-of-life outcome measures and supporting standardized collection and measurement of biofluid biomarkers. These innovations will inform development of future treatments and trials for patients with NMDAR encephalitis and other types of autoimmune encephalitis. The ExTINGUISH trial opened to enrollment of adult patients (older than 18 years) in 2022 and pediatric patients (older than 12 years) in 2024; enrollment is ongoing.

Identifiers

PMID40625668
PMCPMC12233123

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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.