The ExTINGUISH Trial of Inebilizumab in NMDAR Encephalitis

Overview

Determine the difference in the modified Rankin score at 16 weeks in participants with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis treated with "first-line" immunomodulatory therapies provided as standard-of-care, and either inebilizumab (investigational agent) or placebo.

Full Title of Study: “A Phase-2b, Double-Blind, Randomized Controlled Trial to Evaluate the Activity and Safety of Inebilizumab in Anti-Nmda Receptor Encephalitis and Assess Markers of Disease”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: January 2027

Detailed Description

N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most common causes of autoimmune encephalitis, with prevalence exceeding herpes encephalitis in industrialized nations. Typically, the disease affects patients age 10-50 causing prominent psychiatric symptoms, altered consciousness, seizures, movement disorders and life-threatening dysautonomia. Intensive care, including cardiorespiratory support is required in 75% of cases. The diagnosis is confirmed by detection of IgG autoantibodies against central nervous system NMDAR in the cerebrospinal fluid. Despite the severity of the illness, NMDAR encephalitis is a treatable neurological disease, with retrospective case series establishing the benefit of off-label intravenous steroids and immunoglobulins. These treatments are presumed to work through effects on IgG NMDAR autoantibody levels in the CSF, although prospective data informing predictors of treatment responses are limited. Even with prompt treatment, ~50% of patients remain disabled, requiring prolonged hospital admissions. Various off-label therapies have been proposed as "second-line" treatments in NMDAR encephalitis. The majority of second-line treatments target circulating B-cells with various degrees of blood brain penetrance and efficacy, and poor consensus on the timing, dose and route of delivery of candidate agents. High-quality evidence is needed to inform the treatment of NMDAR encephalitis. Inebilizumab is a promising therapeutic monoclonal antibody for the treatment of NMDAR encephalitis. This humanized monoclonal antibody against the B-cell surface antigen CD19 was recently shown to be safe and efficacious in the treatment of neuromyelitis optica spectrum disorder—another antibody-mediated disorder of the central nervous system. Compared to other off label B-cell depleting therapies, such as rituximab, inebilizumab not only depletes CD20+ B-cells, but also CD20- plasmablasts and plasma cells, resulting in robust and sustained suppression of B-cell expression. The ExTINGUISH Trial will randomize 116 participants with moderate-to-severe NMDAR encephalitis to receive either inebilizumab or placebo in addition to first-line therapies. Patient outcomes will be ascertained at standard intervals using the modified Rankin scale and accepted safety measures (primary outcomes at 16 weeks), together with comprehensive validated neuropsychological tests, bedside cognitive screening tools, quality of life/ functional indices, and outcome prediction measures. Clinical data will be combined with quantitative measures of NMDAR autoantibody titers and cytokines implicated in B-cell activation and antibody production within the intrathecal compartment to identify treatment responders, inform the biologic contributors to outcomes, and evaluate for biomarkers that may serve as early predictors of favorable outcomes in future clinical trials in NMDAR encephalitis. The ExTINGUISH Trial will prospectively study an optimized B-cell depletion therapy to promote better long-term outcomes in NMDAR encephalitis, to determine more meaningful cognitive endpoints, and to identify better biologic biomarkers to predict outcome.

Interventions

  • Drug: Inebilizumab
    • RCP: Blinded treatment on Day 1, Day 15, Inebilizumab group: Inebilizumab 300 mg intravenous (IV) Placebo group: IV matching placebo Prior to enrollment, all participants will receive standard of care, including high-dose corticosteroids (minimum of 3 days of treatment, 1 g methylprednisolone daily or equivalent) AND either IVIg (total dose range between 1.2 and 2 g/kg) OR plasmapheresis (defined as 5 or 6 exchanges). Rescue therapy will be given to participants in either treatment group based on the results of the Week 6 assessments. Rescue therapy is cyclophosphamide 750 mg/m2 IV followed by additional doses every 28-30 days until the mRS score is ≤ 3 (at site Principal Investigator’s discretion under standard of care).
  • Drug: Placebo
    • The placebo group will receive IV matching placebo on Day 1 and Day 15,

Arms, Groups and Cohorts

  • Active Comparator: Inebilizumab
    • Approximately 58 patients will receive Inebilizumab in addition to first line immunotherapy. (Approximately 116 participants will be randomized in a 1:1 ratio to 2 treatment groups; approximately 58 participants to each treatment group). All participants will also receive a 3 day course of IVIg.
  • Placebo Comparator: Placebo
    • Approximately 58 patients will receive placebo in addition to first line immunotherapy. (Approximately 116 participants will be randomized in a 1:1 ratio to 2 treatment groups; approximately 58 participants to each treatment group). All participants will also receive a 3 day course of IVIg.

Clinical Trial Outcome Measures

Primary Measures

  • Change of modified Rankin score at 16 weeks
    • Time Frame: 16 weeks
    • 1. Change in modified Rankin score (mRS) at 16 weeks determined by rank analyses, integrating need for rescue therapy and time to achievement of the mRS.
  • Safety profile
    • Time Frame: 96 weeks
    • 2. Inebilizumab safety, as measured by the number of treatment-emergent adverse events and treatment-emergent serious adverse events.

Secondary Measures

  • Time to mRS ≤ 2, corrected for baseline value.
    • Time Frame: 96 weeks
    • Time to mRS ≤ 2, corrected for baseline value.
  • Clinical Assessment Scale in Autoimmune Encephalitis (CASE) Score (continuous logistic regression), corrected from baseline value to week 24 (weeks 6 and 16).
    • Time Frame: 16 weeks
    • Clinical Assessment Scale in Autoimmune Encephalitis (CASE) Score (continuous logistic regression), corrected from baseline value to week 24 (weeks 6 and 16).
  • mRS at week 6 as measured by proportional odds logistic regression/shift analysis.
    • Time Frame: 6 weeks
    • mRS at week 6 as measured by proportional odds logistic regression/shift analysis.
  • Proportion of participants who meet the protocol-defined criteria for needing rescue therapy at week 6.
    • Time Frame: 6 weeks
    • Proportion of participants who meet the protocol-defined criteria for needing rescue therapy at week 6.
  • Cognitive outcome at week 24 as measured by mean scaled score on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) + components of Delis-Kaplan Executive Function System (D-KEFS).
    • Time Frame: 24 weeks
    • Cognitive outcome at week 24 as measured by mean scaled score on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) + components of Delis-Kaplan Executive Function System (D-KEFS).
  • Survival as measured by a Kaplan-Meier analysis.
    • Time Frame: 96 weeks
    • Survival as measured by a Kaplan-Meier analysis.

Participating in This Clinical Trial

Inclusion Criteria

Inclusion Criteria 1. Diagnosis of NMDAR encephalitis, defined by both (a) and (b):

1. A subacute onset of change in mental status consistent with autoimmune encephalitis,

2. A positive cell-based assay for anti-NMDA receptor IgG antibody in the CSF confirmed in study-specified laboratories.

2. Age ≥ 18 years 3. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of America (USA), European Union [EU] Data Privacy Directive in the EU) obtained from the participant/legal representative prior to performing any protocol-related procedures, including screening evaluations.

4. Females of childbearing potential who are sexually active with a nonsterilized male partner must agree to use a highly effective method of contraception beginning at screening or upon discharge from hospitalization/inpatient rehabilitation (for participants who were incapacitated at the time of screening), and to continue precautions for 6 months after the final dose of investigational product.

5. Nonsterilized males who are sexually active with a female partner of childbearing potential must agree to use a highly effective method of contraception at screening or upon discharge from hospitalization/inpatient rehabilitation (for participants who were incapacitated at the time of screening), and to continue precautions for 3 months after the final dose of investigational product. Male patients with female partners of childbearing potential must have that female partner use at least one form of highly effective contraception, starting at least one menstrual cycle before (the male patient's) first study drug administration and continuing until at least 3 months after their male partner's last dose of the study drug.

6. Willing to forego other immunomodulatory therapies (investigational or otherwise) for NMDAR encephalitis during the study.

7. Patient must have received at least 3 days of methylprednisolone 1000 mg IV or equivalent corticosteroid within 30 days prior to randomization (Day 1). In addition, patients must have received EITHER of the following treatments within 30 days before randomization.

1. IVIg, at a minimum dose of 2 g/kg

2. Plasma exchange or plasmapheresis, with a minimum of 5 treatments. NOTE: These treatments may be provided during the screening period, but must be completed prior to randomization.

8. mRS of ≥3 at the screening visit, indicating at least moderate disability. 9. Ability and willingness to attend study visits and complete the study

Exclusion Criteria

1. Any condition that, in the opinion of the investigator, would interfere with the evaluation or administration of the investigational product, interpretation of participant safety or study results, or would make participation in the study an unacceptable risk. This specifically includes recent history (last 5 years) of herpes simplex virus encephalitis or known central nervous system demyelinating disease (e.g., multiple sclerosis).

2. Presence of an active or chronic infection that is serious in the opinion of the investigator.

3. Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 published half-lives of the investigational treatment, whichever is the longer, prior to randomization.

4. Lactating or pregnant females, or females who intend to become pregnant anytime from study enrollment to 6 months following last dose of investigational agent.

5. Known history of allergy or reaction to any component of the investigational agent formulation or history of anaphylaxis following any biologic therapy.

6. At screening (one repeat test may be conducted to confirm results prior to randomization within the same screening period), any of the following:

1. Aspartate transaminase (AST) > 2.5 × upper limit of normal (ULN)

2. Alanine transaminase (ALT) > 2.5 × upper limit of normal (ULN)

3. Total bilirubin > 1.5 × ULN (unless due to Gilbert's syndrome)

4. Platelet count < 75,000/μL (or < 75 × 109/L)

5. Hemoglobin < 8 g/dL (or < 80 g/L)

6. Total white blood count <2,500 cells/mm3

7. Total immunoglobulin < 600 mg/dL

8. Absolute neutrophil count < 1200 cells/μL

9. CD4 T lymphocyte count < 300 cells/µL

7. Receipt of the following at any time prior to randomization:

1. Alemtuzumab

2. Total lymphoid irradiation

3. Bone marrow transplant

4. T-cell vaccination therapy

8. Receipt of rituximab or any experimental B-cell depleting agent, unless the CD19 B-cell level has returned to above the lower limit of normal prior to randomization.

9. Receipt of any of the following within 3 months prior to randomization

1. Natalizumab (Tysabri®)

2. Cyclosporine

3. Methotrexate

4. Mitoxantrone

5. Cyclophosphamide

6. Azathioprine

7. Mycophenolate mofetil

10. Severe drug allergic history or anaphylaxis to two or more food products or medicines (including known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamine, and methylprednisolone or equivalent glucocorticoid).

11. Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as human immunodeficiency virus (HIV) infection or splenectomy that predisposes the participant to infection.

13. Confirmed positive test for hepatitis B serology (hepatitis B surface antigen and core antigen) and/or hepatitis C PCR positive at screening.

14. History of cancer, apart from ovarian or extra-ovarian teratoma (also known as a dermoid cyst) or germ cell tumor, or squamous cell carcinoma of the skin or basal cell carcinoma of the skin. Squamous cell and basal cell carcinomas should be treated with documented success of curative therapy > 3 months prior to randomization.

15. Any live or attenuated vaccine within 3 weeks prior to Day 1 (administration of killed vaccines is acceptable).

16. Bacillus of Calmette and Guérin (BCG) vaccine within 1 year of enrollment. 17. Recurrence of previously treated NMDAR encephalitis within the last 3 or 5 years, or suspicion of symptomatic untreated NMDAR encephalitis of greater than 3 months duration at the time of screening.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Utah
  • Provider of Information About this Clinical Study
    • Principal Investigator: Stacey Clardy MD PhD, Associate Professor – University of Utah
  • Overall Contact(s)
    • Stacey L Clardy, MD, PhD, 8015857575, stacey.clardy@hsc.utah.edu

Citations Reporting on Results

Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013 Feb;12(2):157-65. doi: 10.1016/S1474-4422(12)70310-1. Epub 2013 Jan 3.

Gabilondo I, Saiz A, Galán L, González V, Jadraque R, Sabater L, Sans A, Sempere A, Vela A, Villalobos F, Viñals M, Villoslada P, Graus F. Analysis of relapses in anti-NMDAR encephalitis. Neurology. 2011 Sep 6;77(10):996-9. doi: 10.1212/WNL.0b013e31822cfc6b. Epub 2011 Aug 24.

Dalmau J, Tüzün E, Wu HY, Masjuan J, Rossi JE, Voloschin A, Baehring JM, Shimazaki H, Koide R, King D, Mason W, Sansing LH, Dichter MA, Rosenfeld MR, Lynch DR. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol. 2007 Jan;61(1):25-36.

Dubey D, Pittock SJ, Kelly CR, McKeon A, Lopez-Chiriboga AS, Lennon VA, Gadoth A, Smith CY, Bryant SC, Klein CJ, Aksamit AJ, Toledano M, Boeve BF, Tillema JM, Flanagan EP. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol. 2018 Jan;83(1):166-177. doi: 10.1002/ana.25131.

Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, Dessain SK, Rosenfeld MR, Balice-Gordon R, Lynch DR. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008 Dec;7(12):1091-8. doi: 10.1016/S1474-4422(08)70224-2. Epub 2008 Oct 11.

Gresa-Arribas N, Titulaer MJ, Torrents A, Aguilar E, McCracken L, Leypoldt F, Gleichman AJ, Balice-Gordon R, Rosenfeld MR, Lynch D, Graus F, Dalmau J. Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol. 2014 Feb;13(2):167-77. doi: 10.1016/S1474-4422(13)70282-5. Epub 2013 Dec 18. Erratum in: Lancet Neurol. 2014 Feb;13(2):135.

Guasp M, Módena Y, Armangue T, Dalmau J, Graus F. Clinical features of seronegative, but CSF antibody-positive, anti-NMDA receptor encephalitis. Neurol Neuroimmunol Neuroinflamm. 2020 Jan 3;7(2). pii: e659. doi: 10.1212/NXI.0000000000000659. Print 2020 Mar.

Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011 Jan;10(1):63-74. doi: 10.1016/S1474-4422(10)70253-2. Review.

Cree BAC, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk DM, Fujihara K, Paul F, Cutter GR, Marignier R, Green AJ, Aktas O, Hartung HP, Lublin FD, Drappa J, Barron G, Madani S, Ratchford JN, She D, Cimbora D, Katz E; N-MOmentum study investigators. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019 Oct 12;394(10206):1352-1363. doi: 10.1016/S0140-6736(19)31817-3. Epub 2019 Sep 5.

Hara M, Martinez-Hernandez E, Ariño H, Armangué T, Spatola M, Petit-Pedrol M, Saiz A, Rosenfeld MR, Graus F, Dalmau J. Clinical and pathogenic significance of IgG, IgA, and IgM antibodies against the NMDA receptor. Neurology. 2018 Apr 17;90(16):e1386-e1394. doi: 10.1212/WNL.0000000000005329. Epub 2018 Mar 16.

Warikoo N, Brunwasser SJ, Benz A, Shu HJ, Paul SM, Lewis M, Doherty J, Quirk M, Piccio L, Zorumski CF, Day GS, Mennerick S. Positive Allosteric Modulation as a Potential Therapeutic Strategy in Anti-NMDA Receptor Encephalitis. J Neurosci. 2018 Mar 28;38(13):3218-3229. doi: 10.1523/JNEUROSCI.3377-17.2018. Epub 2018 Feb 23.

Hughes EG, Peng X, Gleichman AJ, Lai M, Zhou L, Tsou R, Parsons TD, Lynch DR, Dalmau J, Balice-Gordon RJ. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci. 2010 Apr 28;30(17):5866-75. doi: 10.1523/JNEUROSCI.0167-10.2010.

Tüzün E, Zhou L, Baehring JM, Bannykh S, Rosenfeld MR, Dalmau J. Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma. Acta Neuropathol. 2009 Dec;118(6):737-43. doi: 10.1007/s00401-009-0582-4.

Matute C, Palma A, Serrano-Regal MP, Maudes E, Barman S, Sánchez-Gómez MV, Domercq M, Goebels N, Dalmau J. N-Methyl-D-Aspartate Receptor Antibodies in Autoimmune Encephalopathy Alter Oligodendrocyte Function. Ann Neurol. 2020 May;87(5):670-676. doi: 10.1002/ana.25699. Epub 2020 Feb 24.

Planagumà J, Leypoldt F, Mannara F, Gutiérrez-Cuesta J, Martín-García E, Aguilar E, Titulaer MJ, Petit-Pedrol M, Jain A, Balice-Gordon R, Lakadamyali M, Graus F, Maldonado R, Dalmau J. Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice. Brain. 2015 Jan;138(Pt 1):94-109. doi: 10.1093/brain/awu310. Epub 2014 Nov 11.

Planagumà J, Haselmann H, Mannara F, Petit-Pedrol M, Grünewald B, Aguilar E, Röpke L, Martín-García E, Titulaer MJ, Jercog P, Graus F, Maldonado R, Geis C, Dalmau J. Ephrin-B2 prevents N-methyl-D-aspartate receptor antibody effects on memory and neuroplasticity. Ann Neurol. 2016 Sep;80(3):388-400. doi: 10.1002/ana.24721. Epub 2016 Aug 2.

Malviya M, Barman S, Golombeck KS, Planagumà J, Mannara F, Strutz-Seebohm N, Wrzos C, Demir F, Baksmeier C, Steckel J, Falk KK, Gross CC, Kovac S, Bönte K, Johnen A, Wandinger KP, Martín-García E, Becker AJ, Elger CE, Klöcker N, Wiendl H, Meuth SG, Hartung HP, Seebohm G, Leypoldt F, Maldonado R, Stadelmann C, Dalmau J, Melzer N, Goebels N. NMDAR encephalitis: passive transfer from man to mouse by a recombinant antibody. Ann Clin Transl Neurol. 2017 Oct 3;4(11):768-783. doi: 10.1002/acn3.444. eCollection 2017 Nov.

Jones BE, Tovar KR, Goehring A, Jalali-Yazdi F, Okada NJ, Gouaux E, Westbrook GL. Autoimmune receptor encephalitis in mice induced by active immunization with conformationally stabilized holoreceptors. Sci Transl Med. 2019 Jul 10;11(500). pii: eaaw0044. doi: 10.1126/scitranslmed.aaw0044.

Rubenstein JL, Combs D, Rosenberg J, Levy A, McDermott M, Damon L, Ignoffo R, Aldape K, Shen A, Lee D, Grillo-Lopez A, Shuman MA. Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment. Blood. 2003 Jan 15;101(2):466-8. Epub 2002 Sep 5.

Muldoon LL, Soussain C, Jahnke K, Johanson C, Siegal T, Smith QR, Hall WA, Hynynen K, Senter PD, Peereboom DM, Neuwelt EA. Chemotherapy delivery issues in central nervous system malignancy: a reality check. J Clin Oncol. 2007 Jun 1;25(16):2295-305. Review.

Mei HE, Frölich D, Giesecke C, Loddenkemper C, Reiter K, Schmidt S, Feist E, Daridon C, Tony HP, Radbruch A, Dörner T. Steady-state generation of mucosal IgA+ plasmablasts is not abrogated by B-cell depletion therapy with rituximab. Blood. 2010 Dec 9;116(24):5181-90. doi: 10.1182/blood-2010-01-266536. Epub 2010 Sep 9.

Dale RC, Pillai S, Brilot F. Cerebrospinal fluid CD19(+) B-cell expansion in N-methyl-D-aspartate receptor encephalitis. Dev Med Child Neurol. 2013 Feb;55(2):191-3. doi: 10.1111/dmcn.12036. Epub 2012 Nov 14.

Makuch M, Wilson R, Al-Diwani A, Varley J, Kienzler AK, Taylor J, Berretta A, Fowler D, Lennox B, Leite MI, Waters P, Irani SR. N-methyl-D-aspartate receptor antibody production from germinal center reactions: Therapeutic implications. Ann Neurol. 2018 Mar;83(3):553-561. doi: 10.1002/ana.25173.

Chen D, Gallagher S, Monson NL, Herbst R, Wang Y. Inebilizumab, a B Cell-Depleting Anti-CD19 Antibody for the Treatment of Autoimmune Neurological Diseases: Insights from Preclinical Studies. J Clin Med. 2016 Nov 24;5(12). pii: E107. Review.

Sanz I. Rationale for B cell targeting in SLE. Semin Immunopathol. 2014 May;36(3):365-75. doi: 10.1007/s00281-014-0430-z. Epub 2014 Apr 25. Review.

Halliley JL, Tipton CM, Liesveld J, Rosenberg AF, Darce J, Gregoretti IV, Popova L, Kaminiski D, Fucile CF, Albizua I, Kyu S, Chiang KY, Bradley KT, Burack R, Slifka M, Hammarlund E, Wu H, Zhao L, Walsh EE, Falsey AR, Randall TD, Cheung WC, Sanz I, Lee FE. Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow. Immunity. 2015 Jul 21;43(1):132-45. doi: 10.1016/j.immuni.2015.06.016. Epub 2015 Jul 14.

Mei HE, Wirries I, Frölich D, Brisslert M, Giesecke C, Grün JR, Alexander T, Schmidt S, Luda K, Kühl AA, Engelmann R, Dürr M, Scheel T, Bokarewa M, Perka C, Radbruch A, Dörner T. A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow. Blood. 2015 Mar 12;125(11):1739-48. doi: 10.1182/blood-2014-02-555169. Epub 2015 Jan 8.

Schuh E, Berer K, Mulazzani M, Feil K, Meinl I, Lahm H, Krane M, Lange R, Pfannes K, Subklewe M, Gürkov R, Bradl M, Hohlfeld R, Kümpfel T, Meinl E, Krumbholz M. Features of Human CD3+CD20+ T Cells. J Immunol. 2016 Aug 15;197(4):1111-7. doi: 10.4049/jimmunol.1600089. Epub 2016 Jul 13.

Herbst R, Wang Y, Gallagher S, Mittereder N, Kuta E, Damschroder M, Woods R, Rowe DC, Cheng L, Cook K, Evans K, Sims GP, Pfarr DS, Bowen MA, Dall'Acqua W, Shlomchik M, Tedder TF, Kiener P, Jallal B, Wu H, Coyle AJ. B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody. J Pharmacol Exp Ther. 2010 Oct;335(1):213-22. doi: 10.1124/jpet.110.168062. Epub 2010 Jul 6. Erratum in: J Pharmacol Exp Ther. 2011 Jan;336(1):294. Dall'Aqua, William [corrected to Dall'Acqua, William].

Agius MA, Klodowska-Duda G, Maciejowski M, Potemkowski A, Li J, Patra K, Wesley J, Madani S, Barron G, Katz E, Flor A. Safety and tolerability of inebilizumab (MEDI-551), an anti-CD19 monoclonal antibody, in patients with relapsing forms of multiple sclerosis: Results from a phase 1 randomised, placebo-controlled, escalating intravenous and subcutaneous dose study. Mult Scler. 2019 Feb;25(2):235-245. doi: 10.1177/1352458517740641. Epub 2017 Nov 16.

Schiopu E, Chatterjee S, Hsu V, Flor A, Cimbora D, Patra K, Yao W, Li J, Streicher K, McKeever K, White B, Katz E, Drappa J, Sweeny S, Herbst R. Safety and tolerability of an anti-CD19 monoclonal antibody, MEDI-551, in subjects with systemic sclerosis: a phase I, randomized, placebo-controlled, escalating single-dose study. Arthritis Res Ther. 2016 Jun 7;18(1):131. doi: 10.1186/s13075-016-1021-2.

Streicher K, Sridhar S, Kuziora M, Morehouse CA, Higgs BW, Sebastian Y, Groves CJ, Pilataxi F, Brohawn PZ, Herbst R, Ranade K. Baseline Plasma Cell Gene Signature Predicts Improvement in Systemic Sclerosis Skin Scores Following Treatment With Inebilizumab (MEDI-551) and Correlates With Disease Activity in Systemic Lupus Erythematosus and Chronic Obstructive Pulmonary Disease. Arthritis Rheumatol. 2018 Dec;70(12):2087-2095. doi: 10.1002/art.40656. Epub 2018 Oct 22.

Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. Erratum in: J Am Geriatr Soc. 2019 Sep;67(9):1991.

Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB: a Frontal Assessment Battery at bedside. Neurology. 2000 Dec 12;55(11):1621-6.

Balu R, McCracken L, Lancaster E, Graus F, Dalmau J, Titulaer MJ. A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis. Neurology. 2019 Jan 15;92(3):e244-e252. doi: 10.1212/WNL.0000000000006783. Epub 2018 Dec 21.

Lim JA, Lee ST, Moon J, Jun JS, Kim TJ, Shin YW, Abdullah S, Byun JI, Sunwoo JS, Kim KT, Yang TW, Lee WJ, Moon HJ, Kim DW, Lim BC, Cho YW, Yang TH, Kim HJ, Kim YS, Koo YS, Park B, Jung KH, Kim M, Park KI, Jung KY, Chu K, Lee SK. Development of the clinical assessment scale in autoimmune encephalitis. Ann Neurol. 2019 Mar;85(3):352-358. doi: 10.1002/ana.25421. Epub 2019 Feb 10.

Lund FE, Garvy BA, Randall TD, Harris DP. Regulatory roles for cytokine-producing B cells in infection and autoimmune disease. Curr Dir Autoimmun. 2005;8:25-54. Review.

Lund FE. Cytokine-producing B lymphocytes-key regulators of immunity. Curr Opin Immunol. 2008 Jun;20(3):332-8. doi: 10.1016/j.coi.2008.03.003. Epub 2008 Apr 15. Review.

Kothur K, Wienholt L, Mohammad SS, Tantsis EM, Pillai S, Britton PN, Jones CA, Angiti RR, Barnes EH, Schlub T, Bandodkar S, Brilot F, Dale RC. Utility of CSF Cytokine/Chemokines as Markers of Active Intrathecal Inflammation: Comparison of Demyelinating, Anti-NMDAR and Enteroviral Encephalitis. PLoS One. 2016 Aug 30;11(8):e0161656. doi: 10.1371/journal.pone.0161656. eCollection 2016.

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