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Abstract Details

The Urgent Need for Evidence Over Anecdote: Equipoise in the ExTINGUISH Clinical Trial in Anti-NMDAR Encephalitis
Autoimmune Neurology
P7 - Poster Session 7 (5:00 PM-6:00 PM)
8-016
Assess whether treatment strategies and patient outcomes in anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) have evolved since the last comprehensive review of the literature in January 2019.
There are no FDA-approved treatments for NMDARE, and no placebo-controlled clinical trials have been completed to provide evidence for management of this disease. Treatment continues to be based on expert opinion and consensus.
A systematic literature review was conducted in PubMed from January 2019 through April 2024. Detailed demographic and clinical information were extracted from English-language articles containing individual data from patients with NMDARE and were compared to previously published studies. Larger studies with ≥10 cases, follow-up duration ≥6 months, and outcomes reported as favorable (mRS 0-2) and poor (mRS 3-5 or 3-6), were grouped and analyzed by diagnosis period: pre-2013 and post-2013.
649 unique patients from 321 articles met the inclusion criteria. Since 2019, both first-line (91.3% vs. 98.3%, p<0.001) and second-line (31.8% vs. 45.3%, p<0.001) immunotherapy use has increased. The proportion of patients receiving initial immunotherapy within 30 days increased from 50.1% to 73.2% (p<0.001). Despite these changes, outcomes showed only slight improvement (mRS 0-2: 71.5% vs. 76.7%, p=0.024) with no significant change in mortality (6.3% vs. 6.9%, p=0.78). Larger cohort studies reported a broad range of favorable outcomes at final follow-up, varying from 66.7–90.9% before 2019 and 56.3–93.3% afterward, reflecting institutional and demographic variability.

Since the last systematic literature review on treatment and outcomes in anti-NMDAR encephalitis was conducted in 2019, significantly more patients are treated early, and receive first- and second-line immunotherapy. Despite these changes in clinical practice, functional outcomes (measured by mRS) have only slightly improved in this time. Marked uncertainty remains regarding the optimal treatment of patients with anti-NMDAR encephalitis; the ExTINGUISH Trial in anti-NMDAR encephalitis will provide much-needed evidence to guide treatment in the future.
Authors/Disclosures
Yoji Hoshina, MD (University of Utah Health)
PRESENTER 		Dr. Hoshina has nothing to disclose.
Tammy L. Smith, MD, PhD (Imaging and Neurosciences Center) Dr. Smith has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. The institution of Dr. Smith has received research support from Alexion/AstraZeneca.
Ka-Ho Wong (U of U Neurology Clinic) The institution of Mr. Wong has received research support from The Sumaira Foundation . The institution of Mr. Wong has received research support from The Siegel Rare Neuroimmune Association.
Lisa K. Peterson, PhD (ARUP Laboratories) Dr. Peterson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Werfen. Dr. Peterson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Werfen. Dr. Peterson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AliveDx. Dr. Peterson has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Clinical Biochemistry. Dr. Peterson has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Lab Q for ASCP. Dr. Peterson has a non-compensated relationship as a President with Association of Medical Laboratory Immunologists that is relevant to AAN interests or activities.
Anastasia Zekeridou, MD, PhD, FAAN (Neuroimmunology Laboratory, Mayo Clinic) The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.
Albert Aboseif, DO (Mayo Clinic Rochester) Dr. Aboseif has received research support from the Eugene & Marcia Applebaum Fellowship Grant.
Christopher Coffey, PhD, FAAN (University of Iowa) Dr. Coffey has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association. The institution of Dr. Coffey has received research support from NIH. The institution of Dr. Coffey has received research support from Michael J Fox Foundation.
Melissa A. Wright, MD (University of Utah) Dr. Wright has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis .
Brenda L. Banwell, MD, FAAN (Johns Hopkins University) Dr. Banwell has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Banwell has received personal compensation in the range of $0-$499 for serving as a Consultant for UCB. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Banwell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Banwell has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Banwell has received research support from National MS Society. The institution of Dr. Banwell has received research support from NIH.
Annalisa Dialino-Felix (Horizon Therapeutics) Ms. Dialino-Felix has received personal compensation for serving as an employee of Amgen.
SUSAN K. FLAVIN (Amgen) Dr. FLAVIN has received personal compensation for serving as an employee of Horizon Therapeutics. Dr. FLAVIN has received personal compensation for serving as an employee of Amgen, Inc. Dr. FLAVIN has stock in Johnson and Johnson. Dr. FLAVIN has stock in Horizon Therapeutics. Dr. FLAVIN has stock in Amgen, Inc. Dr. FLAVIN has received intellectual property interests from a discovery or technology relating to health care.
Lisa Dill Lisa Dill has nothing to disclose.
Hyun J. Cho, MD (NIH) Dr. Cho has nothing to disclose.
Josep O. Dalmau, MD, PhD, FAAN Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas Research Institute of America. Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Research & Development . Dr. Dalmau has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for 好色先生. An immediate family member of Dr. Dalmau has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Dalmau has received research support from Sage Therapeutics. The institution of Dr. Dalmau has received research support from Edmond J.Safra Foundation . The institution of Dr. Dalmau has received research support from La Caixa Foundation. The institution of Dr. Dalmau has received research support from Spanish Ministry of Health (ISCIII). The institution of Dr. Dalmau has received research support from Euroimmun, Inc. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care.
Maarten J. Titulaer, MD, PhD (Erasmus Medical Center) The institution of Dr. Titulaer has received research support from Dutch Epilepsy Foundations (NEF 19-08). The institution of Dr. Titulaer has received research support from CSL Behring. The institution of Dr. Titulaer has received research support from UCB. The institution of Dr. Titulaer has received research support from Netherlands Organisation for Scientific Research (ZonMW, Memorabel initiative and E-RARE UltraAIE) . The institution of Dr. Titulaer has received research support from Horizon Therapeutics / Amgen. The institution of Dr. Titulaer has received research support from Dioraphte (charity). The institution of Dr. Titulaer has received research support from Guidepoint Global LLC. The institution of Dr. Titulaer has received research support from ArgenX. Dr. Titulaer has received intellectual property interests from a discovery or technology relating to health care. Dr. Titulaer has received publishing royalties from a publication relating to health care.
Gregory S. Day, MD, MSc, FAAN (Mayo Clinic) Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for DynaMed (EBSCO Health). Dr. Day has or had stock in ANI Pharmaceuticals. The institution of Dr. Day has received research support from National Institutes of Health / NIA. The institution of Dr. Day has received research support from National Institutes of Health / NINDS. The institution of Dr. Day has received research support from Amgen Pharmaceuticals. The institution of Dr. Day has received research support from AVID Radiopharmaceuticals. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Presenter at Annual Meeting (CME) with 好色先生. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development (CME) with PeerView, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Continuing 好色先生, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Ionis Pharmaceuticals. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a 好色先生al Case Development + Presentation (video) with PeerDirect (P\S\L Group). Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development / Presentation (non-CME) with MJH Life Sciences (NeurologyLive). Dr. Day has a non-compensated relationship as a Clinical Director with Anti-NMDA Receptor Encephalitis Foundation that is relevant to AAN interests or activities.
Stacey Clardy, MD, PhD, FAAN (University of Utah) Dr. Clardy has received personal compensation for serving as an employee of Veterans Health Administration (VHA). Dr. Clardy has received personal compensation for serving as an employee of University of Utah Health. Dr. Clardy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca/Alexion. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen/Horizon. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyverna. Dr. Clardy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology/AAN Publications. The institution of Dr. Clardy has received research support from NIH/NINDS. The institution of Dr. Clardy has received research support from SRNA. The institution of Dr. Clardy has received research support from Alexion/AstraZeneca. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel/Lodging/Honoraria with U of Iowa, Miami, Stanford, Barrow, Beaumont Health, CCF, Emory, Penn State, Mayo Clinic, Walter Reed.